無定型碳酸鈣 (Amorphous calcium carbonate, ACC)是一種天然無毒性的生物礦物，具有pH響應性，生物相容性高，化學成分簡單，製備成本低且易於大規模生產等諸多優點，在生物醫學方面極具應用潛力，可作為藥物載體進行開發。然而，ACC在水溶液中易於溶解和結晶等不穩定因素，限制了此材料在奈米藥物載體方面的未來發展性，因此需要額外添加保護劑對其進行保護。本研究通過簡單的氣相擴散反應，在乙醇溶液中成功合成出了同時載負阿霉素 (Doxorubicin, DOX)與吲哚菁綠 (Indocyanine green, ICG)的ACC奈米藥物載體,其載負率分別為94%和98%，粒徑為46 nm。為維持其水相穩定性，實驗以聚乙烯吡咯烷酮 (Polyvinyl pyrrolidone, PVP)吸附在其表面抑制其結晶，再以植酸 (Phytic acid, IP6)形成Ca-IP6殼層，得到粒徑為78 nm的奈米複合體，并藉由XRD偵測獲知其仍維持ACC形式。進而通過鹽酸羥胺 (Hydroxylamine hydrochloride)還原四氯金酸 (Hydrogen tetrachloroaurate)，在奈米複合體表面緊密修飾上小粒徑 (15 nm)的金奈米粒子, 這些表面修飾的金奈米粒子不僅可以通過巰基修飾的聚乙二醇 (Thiol Polyethylene glycol, PEG-SH) 使其在生理環境下穩定存在，還可以通過其光熱響應特性增強近紅外光熱療。總之，一個具有pH響應特性的雙藥物控制釋放系統被成功的建立並且在腫瘤細胞治療方面得到應用。

Amorphous calcium carbonate (ACC), as a naturally nontoxic biomineral, shows great potential for biomedical applications, with intrinsic advantages of pH-dependent degradability, biocompatibility, simple chemical composition, as well as low cost and ease of large-scale production. However, the major obstacle to develop ACC nanoparticles as a pH-responsive nanomedicine is the high aqueous instability of ACC including its ease of dissolution and phase transition. Herein, an alcoholic suspension of ACC nanoparticles preloaded with doxorubicin (DOX) and indocyanine green (ICG) was obtained using a simple vapor-diffusion process. To preserve their stability while retaining their pH-responsiveness, polypyrrolidone (PVP) and phytic acid (IP6) were introduced to protect the ACC from unexpected crystallization in aqueous environment. The surface of the resulting nanoparticles was further covered with closely packed small Au nanoparticles via hydroxylamine reduction of HAuCl4. The surface coating of Au nanoparticles not only facilitated specific PEGylation through thiol linkages but also the photothermal response in the near-infrared tissue optical window. Overall, a co-drug delivery platform with pH-responsive release capability was successfully established to improve the therapeutic efficacy in tumor cells.

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