Protein-Crowned Micelles for Targeted and Synergistic Tumor-Associated Macrophage Reprogramming to Enhance Cancer Treatment
Protein-Crowned Micelles for Targeted and Synergistic Tumor-Associated Macrophage Reprogramming to Enhance Cancer Treatment
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蛋白质冠胶束用于靶向和协同肿瘤相关巨噬细胞重编程以增强癌症治疗
DOI：
10.1021/acs.nanolett.2c00901
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发表时间：
2022
期刊：
影响因子：
10.8
通讯作者：
Dongfang Zhou
中科院分区：
文献类型：
--
作者：
Jun-Hui Sun;Xiaoling Liang;Manying Cai;Libiao Yan;Zhengju Chen;Lei Guo;Li Jing;Yupeng Wang;Dongfang Zhou
肿瘤相关巨噬细胞（Tumor-associated macrophages，TAMs）是一种很有前途的肿瘤治疗靶点，但实现TAMs的多靶点治疗仍具有挑战性。在这里，我们开发了一种蛋白质冠状胶束系统，用于靶向和协同TAM重编程以增强癌症治疗。具有血红蛋白冠的阿霉素胶束（Hb-DOXM）可以与内源性血浆结合珠蛋白结合，实现特异性M2型TAM靶向。在肿瘤缺氧和酸性环境下，Hb-DOXM可响应性地释放O2和DOX，通过缺氧缓解减少TAMs的募集，并释放DOX杀死M2型TAMs和癌细胞。为了充分地重编程TAM，TAM调节药物塞来昔布被进一步包封（Hb-DOXM@Cel）以重组M2型TAM。Hb-DOXM@Cel的靶向协同TAM重编程可以将肿瘤微环境（TME）重塑为免疫刺激微环境，增强细胞毒性T淋巴细胞的抗肿瘤作用，从而增强基于DOX的化疗效果。蛋白质冠状胶束策略提供了用于增强癌症治疗的靶向和协同TAM治疗工具。
Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancers, but achieving multitarget therapy of TAMs is still challenging. Here, we develop a protein-crowned micelle system for targeted and synergistic TAM reprogramming to enhance cancer treatment. The doxorubicin-loaded micelles with a hemoglobin crown (Hb-DOXM) can bind with endogenous plasma haptoglobin to realize specific M2-type TAM targeting. Under the tumor hypoxic and acidic environments, Hb-DOXM can responsively release O2 and DOX to reduce the recruitment of TAMs by hypoxia remission and release DOX to kill M2-type TAMs and cancer cells. To reprogram TAMs adequately, the TAM-modulating drug celecoxib is further encapsulated (Hb-DOXM@Cel) to repolarize M2-type TAMs. The targeted and synergistic TAM reprogramming by Hb-DOXM@Cel can remodel the tumor microenvironment (TME) to an immunostimulatory microenvironment and augment the antitumor effect of cytotoxic T lymphocyte, thus strongly enhancing the DOX-based chemotherapy. The protein-crowned micelle strategy presents a targeted and synergistic TAM therapy tool for enhanced cancer treatment.