Macrophage-Encapsulated Bioorthogonal Nanozymes for Targeting Cancer Cells.
Macrophage-Encapsulated Bioorthogonal Nanozymes for Targeting Cancer Cells.
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DOI：
10.1021/jacsau.2c00247
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发表时间：
2022-07-25
期刊：
影响因子：
8
通讯作者：
Rotello, Vincent M
中科院分区：
文献类型：
--
作者：
Das, Riddha;Hardie, Joseph;Joshi, Bishnu P;Zhang, Xianzhi;Gupta, Aarohi;Luther, David C;Fedeli, Stefano;Farkas, Michelle E;Rotello, Vincent M
巨噬细胞根据肿瘤细胞分泌的化学引诱剂梯度迁移到肿瘤部位，为癌症治疗提供了一种真正的主动靶向策略。然而，基于巨噬细胞的递送面临着货物装载、释放控制以及载荷对巨噬细胞载体的影响等挑战。我们提出了一种采用具有过渡金属催化剂（tmc）的生物正交“纳米酶”的策略，以提供细胞内“工厂”，将原色素和前药物转化为显像剂和化疗药物。这些纳米酶通过将tmc嵌入自组装的单层涂层金纳米颗粒中来溶解和稳定tmc。传递到巨噬细胞的纳米酶在细胞内定位，即使在长时间（72小时）孵育后仍保持活性。值得注意的是，负载纳米酶的巨噬细胞保持了对肿瘤细胞化学引诱剂的固有迁移能力，有效地杀死了共培养中的癌细胞。这项工作建立了负载纳米酶的巨噬细胞在肿瘤部位激活前药的潜力，提供易于调节的剂量和递送率，同时最大限度地减少化疗药物的脱靶毒性。
Macrophages migrate to tumor sites by following chemoattractant gradients secreted by tumor cells, providing a truly active targeting strategy for cancer therapy. However, macrophage-based delivery faces challenges of cargo loading, control of release, and effects of the payload on the macrophage vehicle. We present a strategy that employs bioorthogonal “nanozymes” featuring transition metal catalysts (TMCs) to provide intracellular “factories” for the conversion of prodyes and prodrugs into imaging agents and chemotherapeutics. These nanozymes solubilize and stabilize the TMCs by embedding them into self-assembled monolayer coating gold nanoparticles. Nanozymes delivered into macrophages were intracellularly localized and retained activity even after prolonged (72 h) incubation. Significantly, nanozyme-loaded macrophages maintained their inherent migratory ability toward tumor cell chemoattractants, efficiently killing cancer cells in cocultures. This work establishes the potential of nanozyme-loaded macrophages for tumor site activation of prodrugs, providing readily tunable dosages and delivery rates while minimizing off-target toxicity of chemotherapeutics.