細菌介導癌症療法（bacteria-mediated tumor therapy, BMTT）已經有數十年的歷史。然而，由於其可能造成的感染風險抑制了細菌介導癌症療法的臨床應用。為了解決這個問題，本實驗提出了一種與細菌型態相似且具有其多功能性的尖刺狀金屬有機框架（Al-Ru metal-organic frameworks, Al-Ru MOFs），此Al-Ru MOFs不僅不會引起感染，且也能展現細菌介導癌症療法的抗癌效果。這種Al-Ru MOFs是由硫酸鋁、三氯化釕及2-胺基對苯二甲酸透過溶劑熱合成反應（solvothermal reaction）所製備而成。根據所使用的反應溫度，其形態將呈現球狀或是尖刺狀，而無論是球狀或尖刺狀的Al-Ru MOFs均可做為光熱劑（photothermal agents），將所吸收的光能轉換為局部熱量。與球狀Al-Ru MOFs相比較，尖刺狀Al-Ru MOFs表面積較大，因此更容易被巨噬細胞吞噬，以引發更強的免疫反應。此外，在腫瘤內部注射Al-Ru MOFs時，尖刺狀Al-Ru MOFs的滯留時間較球狀Al-Ru MOFs還長，這使其可以重複進行光熱療法以用於癌症治療。在抗腫瘤實驗中，我們於小鼠腫瘤內部施打尖刺狀Al-Ru MOFs後，透過照射近紅外光（near infrared, NIR）所引起的溫和高溫來破壞腫瘤，使整個腫瘤轉化為原位癌症疫苗，引發全身性的免疫反應。並且再配合上免疫檢查點抑制劑PD-1的施打，來進行光熱與免疫之複合治療。上述的實驗結果顯示，此原位癌症疫苗與免疫檢查點抑制劑PD-1具有協同作用，可模擬細菌介導癌症療法的抗腫瘤功能，消除原位腫瘤並抑制腫瘤的復發和轉移，具有臨床應用上的潛力。

The purpose of cancer vaccines is to activate tumor-specific T lymphocytes, subsequently causing tumor regression. Most cancer vaccines under development are associated with defined tumor antigens rather than with all antigens of whole tumor cells, limiting the anti-tumor immune responses that they elicit. This work proposes a multifunctional spiky Al-Ru (III) metal-organic frameworks (Al-Ru MOFs) which can absorb near-infrared light (+NIR) to cause mild hyperthermia which can destroy the tumor. The system prepared herein can convert tumor into an in situ cancer vaccine, thereby inducing systemic immune response. In addition, the combination of Al-Ru MOFs with immune checkpoint inhibitors (+PD-1) cause a powerful synergistic effect, alleviating the tumor immunosuppressive microenvironment, generating a robust long-term anti-tumor immunity. According to the in vivo studies, treatments with Al-Ru MOFs/+NIR can suppress the growth of primary tumors, and induce memory responses against subsequent tumor challenge. The combination of Al-Ru MOFs/+NIR with PD-1 can further increase the rate of tumor rejection. Moreover, mice that had been treated with Al-Ru MOFs/+NIR or Al-Ru MOFs＋PD-1/＋NIR and had rejected the tumors can induce long-lasting tumor-specific immune memory responses. These results suggest that the system that is proposed herein is promising for generating cancer vaccines in situ, by using the tumor itself as the antigen source and combining with PD-1 to generate a long-term anti-tumor immunity for preventing tumor recurrence and metastasis.

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