Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment

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• 作者：Yi Wang^a ; ^b ; Yao-Xin Lin^a ; ^b ; Sheng-Lin Qiao^a ; ^b ; Hong-Wei An^a ; ^b ; Yang Ma^a ; ^b ; Zeng-Ying Qiao^a ; R.P. Yeshan J. Rajapaksha^a ; ^b ; Hao Wang^a ; ^b ; ^{wanghao@nanoctr.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nanoparticles ; Self-assembly ; Cancer ; Immunotherapy ; Macrophage
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：112
• 期：Complete
• 页码：153-163
• 全文大小：3905 K

文摘

Immunotherapy has shown promising treatment effects for a variety of cancers. However, the immune treatment efficiency for solid tumors is limited owing to insufficient infiltration of immune cells into solid tumors. The conversion of tumor-supportive macrophages to tumor-suppressive macrophages, inducing the functional reversal of macrophages, is an effective method and contributes to a subsequent antitumor response. The current challenge in the field is the poor distribution and systemic side effects associated with the use of cytokines. As a solution to this issue, we designed and synthesized microenvironment-responsive nanoparticles (P) with IL-12 payload (IL-12⊂P1). These nanoparticles could promote the systemic administration and release of IL-12 in the tumor microenvironment, and the locally responsive property of IL-12⊂P1 could subsequently re-educate tumor-associated macrophages (TAMs). In particular, our results illustrated the great therapeutic effects derived from the functional conversion of macrophages. Our strategy was to design a microenvironment-responsive material for local macrophage modification to overcome the physiological barrier of solid tumors. The shifting of macrophage phenotypes via IL-12⊂P1 achieved immunomodulation in the microenvironment for cancer therapy, with negligible cytotoxicity. We expect that the functional regulation of TAMs by pH-responsive nanomaterials is a promising therapeutic approach for cancer immunotherapy.