Dual-targeting of artesunate and chloroquine to tumor cells and tumor-associated macrophages by a biomimetic PLGA nanoparticle for colorectal cancer treatment.
Dual-targeting of artesunate and chloroquine to tumor cells and tumor-associated macrophages by a biomimetic PLGA nanoparticle for colorectal cancer treatment.
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DOI：
10.1016/j.ijbiomac.2023.125163
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发表时间：
2023-06
影响因子：
8.2
通讯作者：
Jianqing Peng;Jia Zhou;R. Sun;Yan Chen;Di Pan;Qin Wang;Yi Chen;Zipeng Gong;Qianming Du
中科院分区：
文献类型：
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作者：
Jianqing Peng;Jia Zhou;R. Sun;Yan Chen;Di Pan;Qin Wang;Yi Chen;Zipeng Gong;Qianming Du
由于对肿瘤支持微环境的忽视，结直肠癌（CRC）的治疗方案在临床上受到限制。为了将对肿瘤细胞生长和免疫抑制肿瘤微环境（TME）的治疗作用联合收割机结合起来，我们提出了青蒿琥酯（AS）和氯喹（CQ）组合，并开发了基于聚（d，l-丙交酯-共-乙交酯）（PLGA）的仿生纳米颗粒用于双靶向递送药物组合。合成了羟基甲基苯硼酸（HPA）修饰的PLGA，制备了活性氧敏感的仿生纳米粒。通过一种新的表面修饰方法获得的甘露糖修饰的红细胞膜（Man-EM）包覆在AS和CQ负载的HPA核上，以获得仿生纳米颗粒-HPA/AS/CQ@Man-EM。它在抑制CRC肿瘤细胞增殖和通过靶向肿瘤细胞和M2样肿瘤相关巨噬细胞（TAM）逆转TAM表型方面具有很强的前景。在原位CRC小鼠模型中，仿生纳米颗粒显示出在肿瘤组织中的改善的积累，并通过抑制肿瘤细胞生长和TAM的复极化来有效地抑制肿瘤生长。值得注意的是，肿瘤细胞和TAM的不平衡分布是实现显著抗肿瘤效果的关键。本工作提出了一种用于CRC治疗的有效仿生纳米载体。
The regimens on colorectal cancer (CRC) are clinically limited due to the ignorance of tumor-supportive microenvironments. To combine the therapeutic effects on both tumor cells growth and immunosuppressive tumor microenvironments (TME), we propose the artesunate (AS) and chloroquine (CQ) combination and develop a poly (d,l-lactide-co-glycolide) (PLGA)-based biomimetic nanoparticle for dual-targeting delivery of the drug combination. Hydroxymethyl phenylboronic acid conjugated PLGA (HPA) is synthesized to form a reactive oxygen species (ROS)-sensitive core of biomimetic nanoparticles. A mannose-modified erythrocyte membrane (Man-EM) obtained by a novel surface modification method is cloaked on the AS and CQ-loaded HPA core to receive a biomimetic nanoparticle-HPA/AS/CQ@Man-EM. It holds a strong promise in inhibiting the proliferation of CRC tumor cells and reversing the phenotypes of TAMs via targeting both tumor cells and M2-like tumor-associated macrophages (TAMs). Verifying in an orthotopic CRC mouse model, the biomimetic nanoparticles showed improved accumulation at tumor tissues and effectively suppressed the tumor growth via both inhibition of tumor cell growth and repolarization of TAMs. Notably, unbalanced distribution to the tumor cells and TAMs is the key to realize the remarkable anti-tumor effects. This work proposed an effective biomimetic nanocarrier for the CRC treatment.