介孔性二氧化矽奈米粒子(mesoporous silica nanoparticles, MSNs)具有一些優秀的特性，如高比表面積與孔洞體積、獨特的介孔結構與可調孔徑大小、易於表面修飾，與優良的生物相容性等。然而，奈米粒子(NPs)在生物體內的血管中容易被免疫系統視為入侵者，而被網狀內皮系統(reticuloendothelial system, RES)/單核吞噬細胞系統(mononuclear phagocyte system, MPS)清除。因此本研究利用紅血球膜包覆MSNs的方式進行偽裝，延長在體內血液循環的壽命。
　　本研究第一部分先探討紅血球膜對不同大小的MSNs進行包覆的差異。改變styrene的濃度，合成出110-450 nm大小的MSNs，利用比表面積分析儀(surface area and porosimetry analyser, ASAP/BET)和熱重量分析儀(thermogravimetric Analyzer, TGA)分析MSNs的性質，孔洞大小為12 nm；再利用掃描式電子顯微鏡(scanning electron microscopy, SEM)、穿透式電子顯微鏡(transmission electron microscopy, TEM)、表面電位和膠體電泳(SDS-PAGE)去驗證紅血球膜包覆在MSNs的表面，得出包覆在不同大小MSNs上的紅血球膜厚度約9-10 nm。在細胞存活率結果顯示，紅血球膜包覆的MSNs無顯著毒性。在動物實驗中，紅血球膜包覆的大小MSNs的累積程度沒有差異，但大RBCm@MSNs的累積量較小的多4.5倍，顯示出延長血液循環並累積達四天的成果。
　　第二部分將MSNs同時裝載疏水性藥物歐洲紫杉醇(Docetaxel, DTX)和石墨烯量子點(graphene quantum dots, GQD)，裝載量(loading capacity, LC)和包覆率(encapsulation efficiency, EE)分別為72.3%和80.3%。透過近紅外光(808 nm)照射後，裝載GQD可在5分鐘內升溫至65 °C。利用化療與熱療的方式達到協同治療的效果。再利用標靶性蛋白藥物爾必得舒(Erbitux®)修飾在紅血球膜表面，增強對A549(人類肺癌細胞株)的治療效果，在治療後第三天抑制住腫瘤生長。

　　本研究開發出具標靶性紅血球膜包覆介孔性二氧化矽奈米粒子，同時裝載DTX和GQD，經由近紅外光照射，產生化療與熱療的協同治療效果，有效抑制老鼠身上A549腫瘤細胞的生長達19天以上。

Mesoporous silica nanoparticles (MSNs) have some excellent properties, such as high surface areas and large pore volumes, unique mesoporous structure and tunable pore sizes, ease of surface modification, and good biocompatibility. However, nanoparticles (NPs) are introduced to in vivo applications through the bloodstream; they are easily considered as intruders by the innate immune system and cleared by the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS). Therefore, this study utilizesd the approach of erythrocyte membranes (red blood cell membranes, RBCm) coated MSNs camouflage to prolong the circulation lifetime.
In the first study project, RBCm coated different sizes of MSNs were investigated. The sizes of MSNs synthesized were 110-450 nm in different concentration of styrene. The properties of MSNs were first analyzed with surface area and porosimetry analyser (ASAP/BET) and thermogravimetric analyzer (TGA). The pore size of MSNs was 12 nm. Then, we confirmed RBCm coated on the surface of MSNs with scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The thickness of as-prepared RBCm coated MSNs (RBCm@MSNs) were 9-10 nm in different sizes. RBCm@MSNs showed no significant toxicity by cell viability. The accumulative level of RBCm@MSNs in different size were no difference, but amount of big RBCm@MSNs were accumulated 4.5 times more than small one. In vivo experiments, RBCm@MSNs prolonged the blood circulation and accumulated for 4 days.

In the second project, MSNs were loaded hydrophobic drug Docetaxel (DTX) and graphene quantum dots (GQD). The loading capacity (LC) and drug encapsulation efficiency (EE) were 72.3 % and 80.3 %, respectively. GQD loaded MSNs were heated to 65 °C in 5 minutes with near-infrared irradiation (808 nm). GQD loaded MSNs combined chemotherapy and thermal therapy to achieve synergistic therapeutic effects. Then, targeting protein drug, Erbitux, modified on the surface of RBCm to enhance treatment effects to A549 (a human lung carcinoma cell line) cancer cells and inhibited the tumor growth after treatments on the third day.
This study developed targeting RBCm coated MSNs loaded DTX and GQD produced synergistic therapeutic effect of chemotherapy and thermal therapy to inhibit A549 tumor cells on the mice growth with near-infrared irradiation up to 19 days.

1. Qiu, Y.; Park, K., Environment-sensitive hydrogels for drug delivery. Advanced Drug Delivery Reviews 2001, 53 (3), 321-339
2. Jeong, B.; Kim, S. W.; Bae, Y. H., Thermosensitive sol–gel reversible hydrogels. Advanced Drug Delivery Reviews 2002, 54 (1), 37-51
3. Cho, K.; Wang, X.; Nie, S.; Chen, Z.; Shin, D. M., Therapeutic Nanoparticles for Drug Delivery in Cancer. American Association for Cancer Research 2008, 14 (5), 1310-1316
4. Petros, R. A.; DeSimone, J. M., Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov 2010, 9 (8), 615-627
5. Liong, M.; Lu, J.; Kovochich, M.; Xia, T.; Ruehm, S. G.; Nel, A. E.; Tamanoi, F.; Zink, J. I., Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery. ACS Nano 2008, 2 (5), 889-896
6. Ferrari, M., Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 2005, 5 (3), 161-171
7. Trewyn, B. G.; Slowing, I. I.; Giri, S.; Chen, H.-T.; Lin, V. S. Y., Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release. Accounts of Chemical Research 2007, 40 (9), 846-853
8. Farokhzad, O. C.; Langer, R., Impact of Nanotechnology on Drug Delivery. ACS Nano 2009, 3 (1), 16-20
9. Kanapathipillai, M.; Brock, A.; Ingber, D. E., Nanoparticle targeting of anti-cancer drugs that alter intracellular signaling or influence the tumor microenvironment. Advanced Drug Delivery Reviews 2014, 79–80, 107-118
10. Matsumura, Y.; Maeda, H., A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs. Cancer Research 1986, 46 (12 Part 1), 6387-6392
11. Maeda, H.; Seymour, L. W.; Miyamoto, Y., Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo. Bioconjugate Chemistry 1992, 3 (5), 351-362
12. Yang, Y.; Zhou, Z.; He, S.; Fan, T.; Jin, Y.; Zhu, X.; Chen, C.; Zhang, Z.-r.; Huang, Y., Treatment of prostate carcinoma with (Galectin-3)-targeted HPMA copolymer-(G3-C12)-5-Fluorouracil conjugates. Biomaterials 2012, 33 (7), 2260-2271
13. Kim, T.-H.; Mount, C. W.; Gombotz, W. R.; Pun, S. H., The delivery of doxorubicin to 3-D multicellular spheroids and tumors in a murine xenograft model using tumor-penetrating triblock polymeric micelles. Biomaterials 2010, 31 (28), 7386-7397
14. Sanson, C.; Schatz, C.; Le Meins, J.-F.; Soum, A.; Thévenot, J.; Garanger, E.; Lecommandoux, S., A simple method to achieve high doxorubicin loading in biodegradable polymersomes. Journal of Controlled Release 2010, 147 (3), 428-435
15. Iyer, A. K.; Khaled, G.; Fang, J.; Maeda, H., Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discovery Today 2006, 11 (17–18), 812-818
16. Rapoport, N.; Marin, A.; Luo, Y.; Prestwich, G. D.; Muniruzzaman, M., Intracellular Uptake and Trafficking of Pluronic Micelles in Drug‐Sensitive and MDR Cells: Effect on the Intracellular Drug Localization. Journal of Pharmaceutical Sciences 2002, 91 (1), 157-170
17. Rapoport, N.; Gao, Z.; Kennedy, A., Multifunctional Nanoparticles for Combining Ultrasonic Tumor Imaging and Targeted Chemotherapy. Journal of the National Cancer Institute 2007, 99 (14), 1095-1106
18. Matsumura, Y.; Kataoka, K., Preclinical and clinical studies of anticancer agent-incorporating polymer micelles. Cancer Science 2009, 100 (4), 572-579
19. Gradishar, W. J.; Tjulandin, S.; Davidson, N.; Shaw, H.; Desai, N.; Bhar, P.; Hawkins, M.; O'Shaughnessy, J., Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With Polyethylated Castor Oil–Based Paclitaxel in Women With Breast Cancer. Journal of Clinical Oncology 2005, 23 (31), 7794-7803
20. Xiong, M.-H.; Bao, Y.; Yang, X.-Z.; Wang, Y.-C.; Sun, B.; Wang, J., Lipase-Sensitive Polymeric Triple-Layered Nanogel for “On-Demand” Drug Delivery. Journal of the American Chemical Society 2012, 134 (9), 4355-4362
21. Cui, W.; Lu, X.; Cui, K.; Niu, L.; Wei, Y.; Lu, Q., Dual-Responsive Controlled Drug Delivery Based on Ionically Assembled Nanoparticles. Langmuir 2012, 28 (25), 9413-9420
22. Pack, D. W.; Hoffman, A. S.; Pun, S.; Stayton, P. S., Design and development of polymers for gene delivery. Nat Rev Drug Discov 2005, 4 (7), 581-593
23. Frohlich, T.; Wagner, E., Peptide- and polymer-based delivery of therapeutic RNA. Soft Matter 2010, 6 (2), 226-234
24. Miyata, K.; Nishiyama, N.; Kataoka, K., Rational design of smart supramolecular assemblies for gene delivery: chemical challenges in the creation of artificial viruses. Chemical Society Reviews 2012, 41 (7), 2562-2574
25. Upadhyay, K. K.; Bhatt, A. N.; Mishra, A. K.; Dwarakanath, B. S.; Jain, S.; Schatz, C.; Le Meins, J.-F.; Farooque, A.; Chandraiah, G.; Jain, A. K.; Misra, A.; Lecommandoux, S., The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(γ-benzyl l-glutamate)-b-hyaluronan polymersomes. Biomaterials 2010, 31 (10), 2882-2892
26. Tai, W.; Chen, Z.; Barve, A.; Peng, Z.; Cheng, K., A Novel Rapamycin-Polymer Conjugate Based on a New Poly(Ethylene Glycol) Multiblock Copolymer. Pharmaceutical Research 2014, 31 (3), 706-719
27. Nakayama, M.; Okano, T., Multi-targeting cancer chemotherapy using temperature-responsive drug carrier systems. Reactive and Functional Polymers 2011, 71 (3), 235-244
28. Ostacolo, L.; Marra, M.; Ungaro, F.; Zappavigna, S.; Maglio, G.; Quaglia, F.; Abbruzzese, A.; Caraglia, M., In vitro anticancer activity of docetaxel-loaded micelles based on poly(ethylene oxide)-poly(epsilon-caprolactone) block copolymers: Do nanocarrier properties have a role? Journal of Controlled Release 2010, 148 (2), 255-263
29. Mu, C.-F.; Balakrishnan, P.; Cui, F.-D.; Yin, Y.-M.; Lee, Y.-B.; Choi, H.-G.; Yong, C. S.; Chung, S.-J.; Shim, C.-K.; Kim, D.-D., The effects of mixed MPEG–PLA/Pluronic® copolymer micelles on the bioavailability and multidrug resistance of docetaxel. Biomaterials 2010, 31 (8), 2371-2379
30. Lin, W.; Kim, D., pH-Sensitive Micelles with Cross-Linked Cores Formed from Polyaspartamide Derivatives for Drug Delivery. Langmuir 2011, 27 (19), 12090-12097
31. Cheng, Y.; He, C.; Ding, J.; Xiao, C.; Zhuang, X.; Chen, X., Thermosensitive hydrogels based on polypeptides for localized and sustained delivery of anticancer drugs. Biomaterials 2013, 34 (38), 10338-10347
32. Liu, J.; Jiang, Y.; Cui, Y.; Xu, C.; Ji, X.; Luan, Y., Cytarabine-AOT catanionic vesicle-loaded biodegradable thermosensitive hydrogel as an efficient cytarabine delivery system. International Journal of Pharmaceutics 2014, 473 (1–2), 560-571
33. Yu, T.; Liu, X.; Bolcato-Bellemin, A.-L.; Wang, Y.; Liu, C.; Erbacher, P.; Qu, F.; Rocchi, P.; Behr, J.-P.; Peng, L., An Amphiphilic Dendrimer for Effective Delivery of Small Interfering RNA and Gene Silencing In Vitro and In Vivo. Angewandte Chemie International Edition 2012, 51 (34), 8478-8484
34. Gillies, E. R.; Fréchet, J. M. J., Dendrimers and dendritic polymers in drug delivery. Drug Discovery Today 2005, 10 (1), 35-43
35. Svenson, S.; Tomalia, D. A., Dendrimers in biomedical applications—reflections on the field. Advanced Drug Delivery Reviews 2005, 57 (15), 2106-2129
36. Lee, C. C.; MacKay, J. A.; Frechet, J. M. J.; Szoka, F. C., Designing dendrimers for biological applications. Nat Biotech 2005, 23 (12), 1517-1526
37. Wu, C.-H.; Cao, C.; Kim, J. H.; Hsu, C.-H.; Wanebo, H. J.; Bowen, W. D.; Xu, J.; Marshall, J., Trojan-Horse Nanotube On-Command Intracellular Drug Delivery. Nano Letters 2012, 12 (11), 5475-5480
38. Kang, X.; Yang, D.; Ma, P. a.; Dai, Y.; Shang, M.; Geng, D.; Cheng, Z.; Lin, J., Fabrication of Hollow and Porous Structured GdVO4:Dy3+ Nanospheres as Anticancer Drug Carrier and MRI Contrast Agent. Langmuir 2013, 29 (4), 1286-1294
39. Pan, L.; He, Q.; Liu, J.; Chen, Y.; Ma, M.; Zhang, L.; Shi, J., Nuclear-Targeted Drug Delivery of TAT Peptide-Conjugated Monodisperse Mesoporous Silica Nanoparticles. Journal of the American Chemical Society 2012, 134 (13), 5722-5725
40. Ghosh, P.; Han, G.; De, M.; Kim, C. K.; Rotello, V. M., Gold nanoparticles in delivery applications. Advanced Drug Delivery Reviews 2008, 60 (11), 1307-1315
41. Kirn, D. H.; Thorne, S. H., Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nat Rev Cancer 2009, 9 (1), 64-71
42. Wang, Y.; Zhao, Q.; Han, N.; Bai, L.; Li, J.; Liu, J.; Che, E.; Hu, L.; Zhang, Q.; Jiang, T.; Wang, S., Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine: Nanotechnology, Biology and Medicine 2015, 11 (2), 313-327
43. Vallet-Regi, M.; Rámila, A.; del Real, R. P.; Pérez-Pariente, J., A New Property of MCM-41:  Drug Delivery System. Chemistry of Materials 2001, 13 (2), 308-311
44. Hu, Y.; Wang, J.; Zhi, Z.; Jiang, T.; Wang, S., Facile synthesis of 3D cubic mesoporous silica microspheres with a controllable pore size and their application for improved delivery of a water-insoluble drug. Journal of Colloid and Interface Science 2011, 363 (1), 410-417
45. Slowing, I. I.; Vivero-Escoto, J. L.; Wu, C.-W.; Lin, V. S. Y., Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Advanced Drug Delivery Reviews 2008, 60 (11), 1278-1288
46. Barbé, C.; Bartlett, J.; Kong, L.; Finnie, K.; Lin, H. Q.; Larkin, M.; Calleja, S.; Bush, A.; Calleja, G., Silica Particles: A Novel Drug-Delivery System. Advanced Materials 2004, 16 (21), 1959-1966
47. Lai, C.-Y.; Trewyn, B. G.; Jeftinija, D. M.; Jeftinija, K.; Xu, S.; Jeftinija, S.; Lin, V. S. Y., A Mesoporous Silica Nanosphere-Based Carrier System with Chemically Removable CdS Nanoparticle Caps for Stimuli-Responsive Controlled Release of Neurotransmitters and Drug Molecules. Journal of the American Chemical Society 2003, 125 (15), 4451-4459
48. Tarn, D.; Ashley, C. E.; Xue, M.; Carnes, E. C.; Zink, J. I.; Brinker, C. J., Mesoporous Silica Nanoparticle Nanocarriers: Biofunctionality and Biocompatibility. Accounts of Chemical Research 2013, 46 (3), 792-801
49. Hu, Y.; Zhi, Z.; Zhao, Q.; Wu, C.; Zhao, P.; Jiang, H.; Jiang, T.; Wang, S., 3D cubic mesoporous silica microsphere as a carrier for poorly soluble drug carvedilol. Microporous and Mesoporous Materials 2012, 147 (1), 94-101
50. Zhao, Y.; Vivero-Escoto, J. L.; Slowing, I. I.; Trewyn, B. G.; Lin, V. S. Y., Capped mesoporous silica nanoparticles as stimuli-responsive controlled release systems for intracellular drug/gene delivery. Expert Opinion on Drug Delivery 2010, 7 (9), 1013-1029
51. Chen, C.; Geng, J.; Pu, F.; Yang, X.; Ren, J.; Qu, X., Polyvalent Nucleic Acid/Mesoporous Silica Nanoparticle Conjugates: Dual Stimuli-Responsive Vehicles for Intracellular Drug Delivery. Angewandte Chemie International Edition 2011, 50 (4), 882-886
52. Sun, L.; Wang, Y.; Jiang, T.; Zheng, X.; Zhang, J.; Sun, J.; Sun, C.; Wang, S., Novel Chitosan-Functionalized Spherical Nanosilica Matrix As an Oral Sustained Drug Delivery System for Poorly Water-Soluble Drug Carvedilol. ACS Applied Materials & Interfaces 2013, 5 (1), 103-113
53. Nadrah, P.; Porta, F.; Planinsek, O.; Kros, A.; Gaberscek, M., Poly(propylene imine) dendrimer caps on mesoporous silica nanoparticles for redox-responsive release: smaller is better. Physical Chemistry Chemical Physics 2013, 15 (26), 10740-10748
54. Vivero-Escoto, J. L.; Slowing, I. I.; Trewyn, B. G.; Lin, V. S. Y., Mesoporous Silica Nanoparticles for Intracellular Controlled Drug Delivery. Small 2010, 6 (18), 1952-1967
55. Tang, F.; Li, L.; Chen, D., Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery. Advanced Materials 2012, 24 (12), 1504-1534
56. Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C.; Margalit, R.; Langer, R., Nanocarriers as an emerging platform for cancer therapy. Nat Nano 2007, 2 (12), 751-760
57. Wagner, E., Programmed drug delivery: nanosystems for tumor targeting. Expert Opinion on Biological Therapy 2007, 7 (5), 587-593
58. Wang, Y.; Zhao, Q.; Hu, Y.; Sun, L.; Bai, L.; Jiang, T.; Wang, S., Ordered nanoporous silica as carriers for improved delivery of water insoluble drugs: a comparative study between three dimensional and two dimensional macroporous silica. International Journal of Nanomedicine 2013, Volume 8 (1), 4015-4031
59. Hudson, S. P.; Padera, R. F.; Langer, R.; Kohane, D. S., The biocompatibility of mesoporous silicates. Biomaterials 2008, 29 (30), 4045-4055
60. Zhang, Y.; Wang, J.; Bai, X.; Jiang, T.; Zhang, Q.; Wang, S., Mesoporous Silica Nanoparticles for Increasing the Oral Bioavailability and Permeation of Poorly Water Soluble Drugs. Molecular Pharmaceutics 2012, 9 (3), 505-513
61. He, Q.; Shi, J.; Zhu, M.; Chen, Y.; Chen, F., The three-stage in vitro degradation behavior of mesoporous silica in simulated body fluid. Microporous and Mesoporous Materials 2010, 131 (1–3), 314-320
62. García, A.; Colilla, M.; Izquierdo-Barba, I.; Vallet-Regí, M., Incorporation of Phosphorus into Mesostructured Silicas: A Novel Approach to Reduce the SiO2 Leaching in Water. Chemistry of Materials 2009, 21 (18), 4135-4145
63. Souris, J. S.; Lee, C.-H.; Cheng, S.-H.; Chen, C.-T.; Yang, C.-S.; Ho, J.-a. A.; Mou, C.-Y.; Lo, L.-W., Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles. Biomaterials 2010, 31 (21), 5564-5574
64. Lu, J.; Liong, M.; Li, Z.; Zink, J. I.; Tamanoi, F., Biocompatibility, Biodistribution, and Drug-Delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals. Small 2010, 6 (16), 1794-1805
65. Yang, P.; Gai, S.; Lin, J., Functionalized mesoporous silica materials for controlled drug delivery. Chemical Society Reviews 2012, 41 (9), 3679-3698
66. Wu, H.; Zhang, S.; Zhang, J.; Liu, G.; Shi, J.; Zhang, L.; Cui, X.; Ruan, M.; He, Q.; Bu, W., A Hollow-Core, Magnetic, and Mesoporous Double-Shell Nanostructure: In Situ Decomposition/Reduction Synthesis, Bioimaging, and Drug-Delivery Properties. Advanced Functional Materials 2011, 21 (10), 1850-1862
67. Kim, J.; Kim, H. S.; Lee, N.; Kim, T.; Kim, H.; Yu, T.; Song, I. C.; Moon, W. K.; Hyeon, T., Multifunctional Uniform Nanoparticles Composed of a Magnetite Nanocrystal Core and a Mesoporous Silica Shell for Magnetic Resonance and Fluorescence Imaging and for Drug Delivery. Angewandte Chemie International Edition 2008, 47 (44), 8438-8441
68. Ciuleanu, T.; Tsai, C. M.; Tsao, C. J.; Milanowski, J.; Amoroso, D.; Heo, D. S.; Groen, H. J. M.; Szczesna, A.; Chung, C. Y.; Chao, T. Y.; Middleton, G.; Zeaiter, A.; Klingelschmitt, G.; Klughammer, B.; Thatcher, N., A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer. Lung Cancer 2013, 82 (2), 276-281
69. Anwer, K.; Kelly, F. J.; Chu, C.; Fewell, J. G.; Lewis, D.; Alvarez, R. D., Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer. Gynecologic Oncology 2013, 131 (1), 169-173
70. Ow, H.; Larson, D. R.; Srivastava, M.; Baird, B. A.; Webb, W. W.; Wiesner, U., Bright and Stable Core−Shell Fluorescent Silica Nanoparticles. Nano Letters 2005, 5 (1), 113-117
71. Benezra, M.; Penate-Medina, O.; Zanzonico, P. B.; Schaer, D.; Ow, H.; Burns, A.; DeStanchina, E.; Longo, V.; Herz, E.; Iyer, S.; Wolchok, J.; Larson, S. M.; Wiesner, U.; Bradbury, M. S., Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. The Journal of Clinical Investigation 2011, 121 (7), 2768-2780
72. Martínez-Carmona, M.; Colilla, M.; Vallet-Regí, M., Smart Mesoporous Nanomaterials for Antitumor Therapy. Nanomaterials 2015, 5 (4), 1906
73. Maeda, H.; Wu, J.; Sawa, T.; Matsumura, Y.; Hori, K., Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of Controlled Release 2000, 65 (1–2), 271-284
74. Singh, R.; Lillard Jr, J. W., Nanoparticle-based targeted drug delivery. Experimental and Molecular Pathology 2009, 86 (3), 215-223
75. Emerich, D. F.; Thanos, C. G., Targeted nanoparticle-based drug delivery and diagnosis. Journal of Drug Targeting 2007, 15 (3), 163-183
76. Brannon-Peppas, L.; Blanchette, J. O., Nanoparticle and targeted systems for cancer therapy. Advanced Drug Delivery Reviews 2004, 56 (11), 1649-1659
77. Moghimi, S. M.; Hunter, A. C.; Murray, J. C., Long-Circulating and Target-Specific Nanoparticles: Theory to Practice. Pharmacological Reviews 2001, 53 (2), 283-318
78. Davis, M. E.; Chen, Z.; Shin, D. M., Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 2008, 7 (9), 771-782
79. Zolnik, B. S.; González-Fernández, Á.; Sadrieh, N.; Dobrovolskaia, M. A., Minireview: Nanoparticles and the Immune System. Endocrinology 2010, 151 (2), 458-465
80. Singh, R.; Pantarotto, D.; Lacerda, L.; Pastorin, G.; Klumpp, C.; Prato, M.; Bianco, A.; Kostarelos, K., Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proceedings of the National Academy of Sciences of the United States of America 2006, 103 (9), 3357-3362
81. Owens Iii, D. E.; Peppas, N. A., Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. International Journal of Pharmaceutics 2006, 307 (1), 93-102
82. Shubayev, V. I.; Pisanic Ii, T. R.; Jin, S., Magnetic nanoparticles for theragnostics. Advanced Drug Delivery Reviews 2009, 61 (6), 467-477
83. Pino, P. d.; Pelaz, B.; Zhang, Q.; Maffre, P.; Nienhaus, G. U.; Parak, W. J., Protein corona formation around nanoparticles - from the past to the future. Materials Horizons 2014, 1 (3), 301-313
84. Monopoli, M. P.; Aberg, C.; Salvati, A.; Dawson, K. A., Biomolecular coronas provide the biological identity of nanosized materials. Nat Nano 2012, 7 (12), 779-786
85. Walkey, C. D.; Chan, W. C. W., Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chemical Society Reviews 2012, 41 (7), 2780-2799
86. Amoozgar, Z.; Yeo, Y., Recent advances in stealth coating of nanoparticle drug delivery systems. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2012, 4 (2), 219-233
87. Pelaz, B.; Charron, G.; Pfeiffer, C.; Zhao, Y.; de la Fuente, J. M.; Liang, X.-J.; Parak, W. J.; del Pino, P., Interfacing Engineered Nanoparticles with Biological Systems: Anticipating Adverse Nano–Bio Interactions. Small 2013, 9 (9-10), 1573-1584
88. Murthy, A. K.; Stover, R. J.; Hardin, W. G.; Schramm, R.; Nie, G. D.; Gourisankar, S.; Truskett, T. M.; Sokolov, K. V.; Johnston, K. P., Charged Gold Nanoparticles with Essentially Zero Serum Protein Adsorption in Undiluted Fetal Bovine Serum. Journal of the American Chemical Society 2013, 135 (21), 7799-7802
89. Yoo, J.-W.; Irvine, D. J.; Discher, D. E.; Mitragotri, S., Bio-inspired, bioengineered and biomimetic drug delivery carriers. Nat Rev Drug Discov 2011, 10 (7), 521-535
90. Balmert, S. C.; Little, S. R., Biomimetic Delivery with Micro- and Nanoparticles. Advanced Materials 2012, 24 (28), 3757-3778
91. Kennedy, L. C.; Bickford, L. R.; Lewinski, N. A.; Coughlin, A. J.; Hu, Y.; Day, E. S.; West, J. L.; Drezek, R. A., A New Era for Cancer Treatment: Gold-Nanoparticle-Mediated Thermal Therapies. Small 2011, 7 (2), 169-183
92. Åkerman, M. E.; Chan, W. C. W.; Laakkonen, P.; Bhatia, S. N.; Ruoslahti, E., Nanocrystal targeting in vivo. Proceedings of the National Academy of Sciences 2002, 99 (20), 12617-12621
93. Xie, J.; Xu, C.; Kohler, N.; Hou, Y.; Sun, S., Controlled PEGylation of Monodisperse Fe3O4 Nanoparticles for Reduced Non-Specific Uptake by Macrophage Cells. Advanced Materials 2007, 19 (20), 3163-3166
94. Liu, Z.; Robinson, J. T.; Sun, X.; Dai, H., PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs. Journal of the American Chemical Society 2008, 130 (33), 10876-10877
95. Hu, C.-M. J.; Fang, R. H.; Luk, B. T.; Zhang, L., Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies. Nanoscale 2014, 6 (1), 65-75
96. Jokerst, J. V.; Lobovkina, T.; Zare, R. N.; Gambhir, S. S., Nanoparticle PEGylation for imaging and therapy. Nanomedicine 2011, 6 (4), 715-728
97. Hu, C.-M. J.; Fang, R. H.; Zhang, L., Erythrocyte-Inspired Delivery Systems. Advanced Healthcare Materials 2012, 1 (5), 537-547
98. Obermeier, B.; Wurm, F.; Mangold, C.; Frey, H., Multifunctional Poly(ethylene glycol)s. Angewandte Chemie International Edition 2011, 50 (35), 7988-7997
99. Dams, E. T. M.; Laverman, P.; Oyen, W. J. G.; Storm, G.; Scherphof, G. L.; van der Meer, J. W. M.; Corstens, F. H. M.; Boerman, O. C., Accelerated Blood Clearance and Altered Biodistribution of Repeated Injections of Sterically Stabilized Liposomes. Journal of Pharmacology and Experimental Therapeutics 2000, 292 (3), 1071-1079
100. Ishida, T.; Maeda, R.; Ichihara, M.; Irimura, K.; Kiwada, H., Accelerated clearance of PEGylated liposomes in rats after repeated injections. Journal of Controlled Release 2003, 88 (1), 35-42
101. Ishida, T.; Wang, X.; Shimizu, T.; Nawata, K.; Kiwada, H., PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. Journal of Controlled Release 2007, 122 (3), 349-355
102. Ishida, T.; Kiwada, H., Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. International Journal of Pharmaceutics 2008, 354 (1–2), 56-62
103. Ishida, T.; Ichihara, M.; Wang, X.; Yamamoto, K.; Kimura, J.; Majima, E.; Kiwada, H., Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. Journal of Controlled Release 2006, 112 (1), 15-25
104. Armstrong, J. K.; Hempel, G.; Koling, S.; Chan, L. S.; Fisher, T.; Meiselman, H. J.; Garratty, G., Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients. Cancer 2007, 110 (1), 103-111
105. Knop, K.; Hoogenboom, R.; Fischer, D.; Schubert, U. S., Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives. Angewandte Chemie International Edition 2010, 49 (36), 6288-6308
106. Acharya, S.; Sahoo, S. K., PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Advanced Drug Delivery Reviews 2011, 63 (3), 170-183
107. Calderón, M.; Quadir, M. A.; Sharma, S. K.; Haag, R., Dendritic Polyglycerols for Biomedical Applications. Advanced Materials 2010, 22 (2), 190-218
108. Adams, N.; Schubert, U. S., Poly(2-oxazolines) in biological and biomedical application contexts. Advanced Drug Delivery Reviews 2007, 59 (15), 1504-1520
109. Kaneda, Y.; Tsutsumi, Y.; Yoshioka, Y.; Kamada, H.; Yamamoto, Y.; Kodaira, H.; Tsunoda, S.-i.; Okamoto, T.; Mukai, Y.; Shibata, H.; Nakagawa, S.; Mayumi, T., The use of PVP as a polymeric carrier to improve the plasma half-life of drugs. Biomaterials 2004, 25 (16), 3259-3266
110. Yang, W.; Zhang, L.; Wang, S.; White, A. D.; Jiang, S., Functionalizable and ultra stable nanoparticles coated with zwitterionic poly(carboxybetaine) in undiluted blood serum. Biomaterials 2009, 30 (29), 5617-5621
111. Sugihara, S.; Blanazs, A.; Armes, S. P.; Ryan, A. J.; Lewis, A. L., Aqueous Dispersion Polymerization: A New Paradigm for in Situ Block Copolymer Self-Assembly in Concentrated Solution. Journal of the American Chemical Society 2011, 133 (39), 15707-15713
112. Jiang, S.; Cao, Z., Ultralow-Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications. Advanced Materials 2010, 22 (9), 920-932
113. Hu, C.-M. J.; Zhang, L.; Aryal, S.; Cheung, C.; Fang, R. H.; Zhang, L., Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proceedings of the National Academy of Sciences 2011, 108 (27), 10980-10985
114. Muzykantov, V. R., Drug delivery by red blood cells: vascular carriers designed by mother nature. Expert Opinion on Drug Delivery 2010, 7 (4), 403-427
115. Oldenborg, P.-A.; Zheleznyak, A.; Fang, Y.-F.; Lagenaur, C. F.; Gresham, H. D.; Lindberg, F. P., Role of CD47 as a Marker of Self on Red Blood Cells. Science 2000, 288 (5473), 2051-2054
116. Rodriguez, P. L.; Harada, T.; Christian, D. A.; Pantano, D. A.; Tsai, R. K.; Discher, D. E., Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles. Science 2013, 339 (6122), 971-975
117. Tsai, R. K.; Rodriguez, P. L.; Discher, D. E., Self inhibition of phagocytosis: The affinity of ‘marker of self’ CD47 for SIRPα dictates potency of inhibition but only at low expression levels. Blood Cells, Molecules, and Diseases 2010, 45 (1), 67-74
118. Zalman, L. S.; Wood, L. M.; Müller-Eberhard, H. J., Isolation of a human erythrocyte membrane protein capable of inhibiting expression of homologous complement transmembrane channels. Proceedings of the National Academy of Sciences 1986, 83 (18), 6975-6979
119. Schönermark, S.; Rauterberg, E. W.; Shin, M. L.; Löke, S.; Roelcke, D.; Hänsch, G. M., Homologous species restriction in lysis of human erythrocytes: a membrane-derived protein with C8-binding capacity functions as an inhibitor. The Journal of Immunology 1986, 136 (5), 1772-6
120. Kim, D. D.; Miwa, T.; Kimura, Y.; Schwendener, R. A.; van Lookeren Campagne, M.; Song, W.-C., Deficiency of decay-accelerating factor and complement receptor 1–related gene/protein y on murine platelets leads to complement-dependent clearance by the macrophage phagocytic receptor CRIg. Blood 2008, 112 (4), 1109-1119
121. Fearon, D. T., Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane. Proceedings of the National Academy of Sciences 1979, 76 (11), 5867-5871
122. Davies, A.; Simmons, D. L.; Hale, G.; Harrison, R. A.; Tighe, H.; Lachmann, P. J.; Waldmann, H., CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. The Journal of Experimental Medicine 1989, 170 (3), 637-654
123. Iida, K.; Nussenzweig, V., Complement receptor is an inhibitor of the complement cascade. The Journal of Experimental Medicine 1981, 153 (5), 1138-1150
124. Nicholson-Weller, A.; Burge, J.; Fearon, D. T.; Weller, P. F.; Austen, K. F., Isolation of a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3 convertases of the complement system. The Journal of Immunology 1982, 129 (1), 184-9
125. Sugita, Y.; Nakano, Y.; Tomita, M., Isolation from Human Erythrocytes of a New Membrane Protein Which Inhibits the Formation of Complement Transmembrane Channels. Journal of Biochemistry 1988, 104 (4), 633-637
126. Holguin, M. H.; Fredrick, L. R.; Bernshaw, N. J.; Wilcox, L. A.; Parker, C. J., Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. The Journal of Clinical Investigation 84 (1), 7-17
127. Okada, N.; Harada, R.; Fujita, T.; Okada, H., Monoclonal antibodies capable of causing hemolysis of neuraminidase-treated human erythrocytes by homologous complement. The Journal of Immunology 1989, 143 (7), 2262-6
128. Oldenborg, P.-A.; Gresham, H. D.; Lindberg, F. P., Cd47-Signal Regulatory Protein α (Sirpα) Regulates Fcγ and Complement Receptor–Mediated Phagocytosis. The Journal of Experimental Medicine 2001, 193 (7), 855-862
129. Luk, B. T.; Jack Hu, C.-M.; Fang, R. H.; Dehaini, D.; Carpenter, C.; Gao, W.; Zhang, L., Interfacial interactions between natural RBC membranes and synthetic polymeric nanoparticles. Nanoscale 2014, 6 (5), 2730-2737
130. Aryal, S.; Hu, C.-M. J.; Fang, R. H.; Dehaini, D.; Carpenter, C.; Zhang, D.-E.; Zhang, L., Erythrocyte membrane-cloaked polymeric nanoparticles for controlled drug loading and release. Nanomedicine 2013, 8 (8), 1271-1280
131. Gao, W.; Hu, C.-M. J.; Fang, R. H.; Luk, B. T.; Su, J.; Zhang, L., Surface Functionalization of Gold Nanoparticles with Red Blood Cell Membranes. Advanced Materials 2013, 25 (26), 3549-3553
132. Hu, C.-M. J.; Fang, R. H.; Copp, J.; Luk, B. T.; Zhang, L., A biomimetic nanosponge that absorbs pore-forming toxins. Nat Nano 2013, 8 (5), 336-340
133. Hu, C.-M. J.; Fang, R. H.; Luk, B. T.; Zhang, L., Nanoparticle-detained toxins for safe and effective vaccination. Nat Nano 2013, 8 (12), 933-938
134. Copp, J. A.; Fang, R. H.; Luk, B. T.; Hu, C.-M. J.; Gao, W.; Zhang, K.; Zhang, L., Clearance of pathological antibodies using biomimetic nanoparticles. Proceedings of the National Academy of Sciences 2014, 111 (37), 13481-13486
135. Hu, C.-M. J.; Fang, R. H.; Luk, B. T.; Chen, K. N. H.; Carpenter, C.; Gao, W.; Zhang, K.; Zhang, L., 'Marker-of-self' functionalization of nanoscale particles through a top-down cellular membrane coating approach. Nanoscale 2013, 5 (7), 2664-2668
136. Gao, W.; Zhang, L., Engineering red-blood-cell-membrane–coated nanoparticles for broad biomedical applications. AIChE Journal 2015, 61 (3), 738-746
137. Pang, Z.; Hu, C.-M. J.; Fang, R. H.; Luk, B. T.; Gao, W.; Wang, F.; Chuluun, E.; Angsantikul, P.; Thamphiwatana, S.; Lu, W.; Jiang, X.; Zhang, L., Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers. ACS Nano 2015, 9 (6), 6450-6458
138. Parodi, A.; Quattrocchi, N.; van de Ven, A. L.; Chiappini, C.; Evangelopoulos, M.; Martinez, J. O.; Brown, B. S.; Khaled, S. Z.; Yazdi, I. K.; Enzo, M. V.; Isenhart, L.; Ferrari, M.; Tasciotti, E., Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nano 2013, 8 (1), 61-68
139. Piao, J.-G.; Wang, L.; Gao, F.; You, Y.-Z.; Xiong, Y.; Yang, L., Erythrocyte Membrane Is an Alternative Coating to Polyethylene Glycol for Prolonging the Circulation Lifetime of Gold Nanocages for Photothermal Therapy. ACS Nano 2014, 8 (10), 10414-10425
140. Li, L.-L.; Xu, J.-H.; Qi, G.-B.; Zhao, X.; Yu, F.; Wang, H., Core–Shell Supramolecular Gelatin Nanoparticles for Adaptive and “On-Demand” Antibiotic Delivery. ACS Nano 2014, 8 (5), 4975-4983
141. Rao, L.; Bu, L.-L.; Xu, J.-H.; Cai, B.; Yu, G.-T.; Yu, X.; He, Z.; Huang, Q.; Li, A.; Guo, S.-S.; Zhang, W.-F.; Liu, W.; Sun, Z.-J.; Wang, H.; Wang, T.-H.; Zhao, X.-Z., Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance. Small 2015, 11 (46), 6225-6236
142. Lang, R.; Jun-Hua, X.; Bo, C.; Huiqin, L.; Ming, L.; Yan, J.; Liang, X.; Shi-Shang, G.; Wei, L.; Xing-Zhong, Z., Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake. Nanotechnology 2016, 27 (8), 085106
143. Ren, X.; Zheng, R.; Fang, X.; Wang, X.; Zhang, X.; Yang, W.; Sha, X., Red blood cell membrane camouflaged magnetic nanoclusters for imaging-guided photothermal therapy. Biomaterials 2016, 92, 13-24
144. Danquah, M. K.; Zhang, X. A.; Mahato, R. I., Extravasation of polymeric nanomedicines across tumor vasculature. Advanced Drug Delivery Reviews 2011, 63 (8), 623-639
145. Jain, R. K., Barriers to drug delivery in solid tumors. Scientific American 1994, 271 (1), 58-65
146. Brown, J. M.; Wilson, W. R., Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004, 4 (6), 437-447
147. Vaupel, P.; Harrison, L., Tumor Hypoxia: Causative Factors, Compensatory Mechanisms, and Cellular Response. The Oncologist 2004, 9 (suppl 5), 4-9
148. Moulder, J. E.; Rockwell, S., Tumor hypoxia: its impact on cancer therapy. Cancer and Metastasis Reviews 1987, 5 (4), 313-341
149. Harris, A. L., Hypoxia [mdash] a key regulatory factor in tumour growth. Nat Rev Cancer 2002, 2 (1), 38-47
150. Dean, M.; Fojo, T.; Bates, S., Tumour stem cells and drug resistance. Nat Rev Cancer 2005, 5 (4), 275-284
151. Zhang, L.; Wang, Y.; Yang, Y.; Liu, Y.; Ruan, S.; Zhang, Q.; Tai, X.; Chen, J.; Xia, T.; Qiu, Y.; Gao, H.; He, Q., High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by Depletion of Tumor Collagen I in Breast Cancer. ACS Applied Materials & Interfaces 2015, 7 (18), 9691-9701
152. Ozcelikkale, A.; Ghosh, S.; Han, B., Multifaceted Transport Characteristics of Nanomedicine: Needs for Characterization in Dynamic Environment. Molecular Pharmaceutics 2013, 10 (6), 2111-2126
153. Sun, Q.; Sun, X.; Ma, X.; Zhou, Z.; Jin, E.; Zhang, B.; Shen, Y.; Van Kirk, E. A.; Murdoch, W. J.; Lott, J. R.; Lodge, T. P.; Radosz, M.; Zhao, Y., Integration of Nanoassembly Functions for an Effective Delivery Cascade for Cancer Drugs. Advanced Materials 2014, 26 (45), 7615-7621
154. Khawar, I. A.; Kim, J. H.; Kuh, H.-J., Improving drug delivery to solid tumors: Priming the tumor microenvironment. Journal of Controlled Release 2015, 201, 78-89
155. Li, L.; Sun, J.; He, Z., Deep Penetration of Nanoparticulate Drug Delivery Systems into Tumors: Challenges and Solutions. Current Medicinal Chemistry 2013, 20 (23), 2881-2891
156. Hobbs, S. K.; Monsky, W. L.; Yuan, F.; Roberts, W. G.; Griffith, L.; Torchilin, V. P.; Jain, R. K., Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proceedings of the National Academy of Sciences 1998, 95 (8), 4607-4612
157. Hashizume, H.; Baluk, P.; Morikawa, S.; McLean, J. W.; Thurston, G.; Roberge, S.; Jain, R. K.; McDonald, D. M., Openings between Defective Endothelial Cells Explain Tumor Vessel Leakiness. The American Journal of Pathology 2000, 156 (4), 1363-1380
158. Fang, J.; Nakamura, H.; Maeda, H., The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Advanced Drug Delivery Reviews 2011, 63 (3), 136-151
159. Tong, R.; Chiang, H. H.; Kohane, D. S., Photoswitchable nanoparticles for in vivo cancer chemotherapy. Proceedings of the National Academy of Sciences 2013, 110 (47), 19048-19053
160. Ju, C.; Mo, R.; Xue, J.; Zhang, L.; Zhao, Z.; Xue, L.; Ping, Q.; Zhang, C., Sequential Intra-Intercellular Nanoparticle Delivery System for Deep Tumor Penetration. Angewandte Chemie International Edition 2014, 53 (24), 6253-6258
161. Bertrand, N.; Wu, J.; Xu, X.; Kamaly, N.; Farokhzad, O. C., Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology. Advanced Drug Delivery Reviews 2014, 66, 2-25
162. Vlashi, E.; Kelderhouse, L. E.; Sturgis, J. E.; Low, P. S., Effect of Folate-Targeted Nanoparticle Size on Their Rates of Penetration into Solid Tumors. ACS Nano 2013, 7 (10), 8573-8582
163. Danhier, F.; Feron, O.; Préat, V., To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. Journal of Controlled Release 2010, 148 (2), 135-146
164. Provenzano, P. P.; Eliceiri, K. W.; Campbell, J. M.; Inman, D. R.; White, J. G.; Keely, P. J., Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Medicine 2006, 4 (1), 1-15
165. Popović, Z.; Liu, W.; Chauhan, V. P.; Lee, J.; Wong, C.; Greytak, A. B.; Insin, N.; Nocera, D. G.; Fukumura, D.; Jain, R. K.; Bawendi, M. G., A Nanoparticle Size Series for In Vivo Fluorescence Imaging. Angewandte Chemie International Edition 2010, 49 (46), 8649-8652
166. Perrault, S. D.; Walkey, C.; Jennings, T.; Fischer, H. C.; Chan, W. C. W., Mediating Tumor Targeting Efficiency of Nanoparticles Through Design. Nano Letters 2009, 9 (5), 1909-1915
167. Jain, R. K., Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy. Science 2005, 307 (5706), 58-62
168. Baish, J. W.; Gazit, Y.; Berk, D. A.; Nozue, M.; Baxter, L. T.; Jain, R. K., Role of Tumor Vascular Architecture in Nutrient and Drug Delivery: An Invasion Percolation-Based Network Model. Microvascular Research 1996, 51 (3), 327-346
169. Manzoor, A. A.; Lindner, L. H.; Landon, C. D.; Park, J.-Y.; Simnick, A. J.; Dreher, M. R.; Das, S.; Hanna, G.; Park, W.; Chilkoti, A.; Koning, G. A.; ten Hagen, T. L. M.; Needham, D.; Dewhirst, M. W., Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors. Cancer Research 2012, 72 (21), 5566-5575
170. Tailor, T. D.; Hanna, G.; Yarmolenko, P. S.; Dreher, M. R.; Betof, A. S.; Nixon, A. B.; Spasojevic, I.; Dewhirst, M. W., Effect of Pazopanib on Tumor Microenvironment and Liposome Delivery. American Association for Cancer Research 2010, 9 (6), 1798-1808
171. Dreher, M. R.; Liu, W.; Michelich, C. R.; Dewhirst, M. W.; Yuan, F.; Chilkoti, A., Tumor Vascular Permeability, Accumulation, and Penetration of Macromolecular Drug Carriers. Journal of the National Cancer Institute 2006, 98 (5), 335-344
172. Wong, C.; Stylianopoulos, T.; Cui, J.; Martin, J.; Chauhan, V. P.; Jiang, W.; Popović, Z.; Jain, R. K.; Bawendi, M. G.; Fukumura, D., Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proceedings of the National Academy of Sciences 2011, 108 (6), 2426-2431
173. Huang, K.; Ma, H.; Liu, J.; Huo, S.; Kumar, A.; Wei, T.; Zhang, X.; Jin, S.; Gan, Y.; Wang, P. C.; He, S.; Zhang, X.; Liang, X.-J., Size-Dependent Localization and Penetration of Ultrasmall Gold Nanoparticles in Cancer Cells, Multicellular Spheroids, and Tumors in Vivo. ACS Nano 2012, 6 (5), 4483-4493
174. CabralH; MatsumotoY; MizunoK; ChenQ; MurakamiM; KimuraM; TeradaY; Kano, M. R.; MiyazonoK; UesakaM; NishiyamaN; KataokaK, Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nano 2011, 6 (12), 815-823
175. Tang, L.; Fan, T. M.; Borst, L. B.; Cheng, J., Synthesis and Biological Response of Size-Specific, Monodisperse Drug–Silica Nanoconjugates. ACS Nano 2012, 6 (5), 3954-3966
176. Yu, S.; Zhang, Y.; Wang, X.; Zhen, X.; Zhang, Z.; Wu, W.; Jiang, X., Synthesis of Paclitaxel-Conjugated β-Cyclodextrin Polyrotaxane and Its Antitumor Activity. Angewandte Chemie International Edition 2013, 52 (28), 7272-7277
177. Stylianopoulos, T.; Wong, C.; Bawendi, M. G.; Jain, R. K.; Fukumura, D., Chapter six - Multistage Nanoparticles for Improved Delivery into Tumor Tissue. In Methods in Enzymology, Nejat, D., Ed. Academic Press: 2012; Vol. Volume 508, pp 109-130.
178. Yuan, F.; Dellian, M.; Fukumura, D.; Leunig, M.; Berk, D. A.; Jain, R. K.; Torchilin, V. P., Vascular Permeability in a Human Tumor Xenograft: Molecular Size Dependence and Cutoff Size. Cancer Research 1995, 55 (17), 3752-3756
179. Jiang, W.; KimBetty, Y. S.; Rutka, J. T.; ChanWarren, C. W., Nanoparticle-mediated cellular response is size-dependent. Nat Nano 2008, 3 (3), 145-150
180. Pan, D.; Zhang, J.; Li, Z.; Wu, M., Hydrothermal Route for Cutting Graphene Sheets into Blue-Luminescent Graphene Quantum Dots. Advanced Materials 2010, 22 (6), 734-738
181. Cheng, H.; Zhao, Y.; Fan, Y.; Xie, X.; Qu, L.; Shi, G., Graphene-Quantum-Dot Assembled Nanotubes: A New Platform for Efficient Raman Enhancement. ACS Nano 2012, 6 (3), 2237-2244
182. Shen, J.; Zhu, Y.; Yang, X.; Li, C., Graphene quantum dots: emergent nanolights for bioimaging, sensors, catalysis and photovoltaic devices. Chemical Communications 2012, 48 (31), 3686-3699
183. Liu, R.; Wu, D.; Feng, X.; Müllen, K., Bottom-Up Fabrication of Photoluminescent Graphene Quantum Dots with Uniform Morphology. Journal of the American Chemical Society 2011, 133 (39), 15221-15223
184. Tu, Y.; Lv, M.; Xiu, P.; Huynh, T.; Zhang, M.; Castelli, M.; Liu, Z.; Huang, Q.; Fan, C.; Fang, H.; Zhou, R., Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets. Nat Nano 2013, 8 (8), 594-601
185. Yang, K.; Zhang, S.; Zhang, G.; Sun, X.; Lee, S.-T.; Liu, Z., Graphene in Mice: Ultrahigh In Vivo Tumor Uptake and Efficient Photothermal Therapy. Nano Letters 2010, 10 (9), 3318-3323
186. Shen, B.; Zhai, W.; Lu, D.; Wang, J.; Zheng, W., Ultrasonication-assisted direct functionalization of graphene with macromolecules. RSC Advances 2012, 2 (11), 4713-4719
187. Zeng, X.; Tao, W.; Mei, L.; Huang, L.; Tan, C.; Feng, S.-S., Cholic acid-functionalized nanoparticles of star-shaped PLGA-vitamin E TPGS copolymer for docetaxel delivery to cervical cancer. Biomaterials 2013, 34 (25), 6058-6067
188. Liu, H.; Chen, D.; Li, L.; Liu, T.; Tan, L.; Wu, X.; Tang, F., Multifunctional Gold Nanoshells on Silica Nanorattles: A Platform for the Combination of Photothermal Therapy and Chemotherapy with Low Systemic Toxicity. Angewandte Chemie 2011, 123 (4), 921-925
189. Yokoi, T.; Sakamoto, Y.; Terasaki, O.; Kubota, Y.; Okubo, T.; Tatsumi, T., Periodic arrangement of silica nanospheres assisted by amino acids. Journal of the American Chemical Society 2006, 128 (42), 13664-13665
190. Eylar, E. H.; Madoff, M. A.; Brody, O. V.; Oncley, J. L., The Contribution of Sialic Acid to the Surface Charge of the Erythrocyte. Journal of Biological Chemistry 1962, 237 (6), 1992-2000
191. Wang, Y.; Liu, Y.; Luehmann, H.; Xia, X.; Brown, P.; Jarreau, C.; Welch, M.; Xia, Y., Evaluating the Pharmacokinetics and In Vivo Cancer Targeting Capability of Au Nanocages by Positron Emission Tomography Imaging. ACS Nano 2012, 6 (7), 5880-5888
192. Wang, Y.; Black, K. C. L.; Luehmann, H.; Li, W.; Zhang, Y.; Cai, X.; Wan, D.; Liu, S.-Y.; Li, M.; Kim, P.; Li, Z.-Y.; Wang, L. V.; Liu, Y.; Xia, Y., Comparison Study of Gold Nanohexapods, Nanorods, and Nanocages for Photothermal Cancer Treatment. ACS Nano 2013, 7 (3), 2068-2077
193. Mukohara, T.; Engelman, J. A.; Hanna, N. H.; Yeap, B. Y.; Kobayashi, S.; Lindeman, N.; Halmos, B.; Pearlberg, J.; Tsuchihashi, Z.; Cantley, L. C.; Tenen, D. G.; Johnson, B. E.; Jänne, P. A., Differential Effects of Gefitinib and Cetuximab on Non–small-cell Lung Cancers Bearing Epidermal Growth Factor Receptor Mutations. Journal of the National Cancer Institute 2005, 97 (16), 1185-1194
194. Raben, D.; Helfrich, B.; Chan, D. C.; Ciardiello, F.; Zhao, L.; Franklin, W.; Barón, A. E.; Zeng, C.; Johnson, T. K.; Bunn, P. A., The Effects of Cetuximab Alone and in Combination With Radiation and/or Chemotherapy in Lung Cancer. American Association for Cancer Research 2005, 11 (2), 795-805
195. Wild, R.; Fager, K.; Flefleh, C.; Kan, D.; Inigo, I.; Castaneda, S.; Luo, F.; Camuso, A.; McGlinchey, K.; Rose, W. C., Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels. American Association for Cancer Research 2006, 5 (1), 104-113
196. Torchilin, V., Tumor delivery of macromolecular drugs based on the EPR effect. Advanced Drug Delivery Reviews 2011, 63 (3), 131-135
197. Chittasupho, C.; Lirdprapamongkol, K.; Kewsuwan, P.; Sarisuta, N., Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist conjugated PLGA nanoparticles. European Journal of Pharmaceutics and Biopharmaceutics 2014, 88 (2), 529-538
198. Chen, L.; Merzlyakov, M.; Cohen, T.; Shai, Y.; Hristova, K., Energetics of ErbB1 Transmembrane Domain Dimerization in Lipid Bilayers. Biophysical Journal 2009, 96 (11), 4622-4630
199. Liao, H.-J.; Carpenter, G., Cetuximab/C225-Induced Intracellular Trafficking of Epidermal Growth Factor Receptor. Cancer Research 2009, 69 (15), 6179-6183
200. Kutty, R. V.; Feng, S.-S., Cetuximab conjugated vitamin E TPGS micelles for targeted delivery of docetaxel for treatment of triple negative breast cancers. Biomaterials 2013, 34 (38), 10160-10171
201. Graf, D.; Molitor, F.; Ensslin, K.; Stampfer, C.; Jungen, A.; Hierold, C.; Wirtz, L., Spatially Resolved Raman Spectroscopy of Single- and Few-Layer Graphene. Nano Letters 2007, 7 (2), 238-242
202. Calizo, I.; Balandin, A. A.; Bao, W.; Miao, F.; Lau, C. N., Temperature Dependence of the Raman Spectra of Graphene and Graphene Multilayers. Nano Letters 2007, 7 (9), 2645-2649
203. Kudin, K. N.; Ozbas, B.; Schniepp, H. C.; Prud'homme, R. K.; Aksay, I. A.; Car, R., Raman Spectra of Graphite Oxide and Functionalized Graphene Sheets. Nano Letters 2008, 8 (1), 36-41
204. Meng, H.; Xue, M.; Xia, T.; Zhao, Y.-L.; Tamanoi, F.; Stoddart, J. F.; Zink, J. I.; Nel, A. E., Autonomous in Vitro Anticancer Drug Release from Mesoporous Silica Nanoparticles by pH-Sensitive Nanovalves. Journal of the American Chemical Society 2010, 132 (36), 12690-12697
205. Chung, T.-H.; Wu, S.-H.; Yao, M.; Lu, C.-W.; Lin, Y.-S.; Hung, Y.; Mou, C.-Y.; Chen, Y.-C.; Huang, D.-M., The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells. Biomaterials 2007, 28 (19), 2959-2966
206. Muñoz, B.; Rámila, A.; Pérez-Pariente, J.; Díaz, I.; Vallet-Regí, M., MCM-41 Organic Modification as Drug Delivery Rate Regulator. Chemistry of Materials 2003, 15 (2), 500-503
207. Barth, R. F.; Kaur, B., Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. Journal of Neuro-Oncology 2009, 94 (3), 299-312