Polymeric nanoparticles enable reversing macrophage in tumor microenvironment for immunotherapy

Publication date: January 2017
Source:Biomaterials, Volume 112
Author(s): Yi Wang, Yao-Xin Lin, Sheng-Lin Qiao, Hong-Wei An, Yang Ma, Zeng-Ying Qiao, R.P.Yeshan J. Rajapaksha, Hao Wang
Immunotherapy has shown a promising effect for a variety of cancers. However, the immune treatment efficiency of solid tumor is limited due to barely infiltration of immune cells in solid tumor. Researchers realized conversion of tumor supportive macrophages to tumor against ones was an effective method to induce the functional reverse of macrophage and contributed to the subsequent antitumor response. The current challenge in the field is that while making use of cytokines usually coupled with poor-distribution and systemic side effects. As a solution to this issue, we designed and synthesized microenvironment-responsive nanoparticles (P) with IL-12 payload (IL-12⊂P1), the IL-12⊂P1 which could adopt by systemic administration and release IL-12 in the tumor microenvironment, the local-responsive property of IL-12⊂P1 re-educate tumor-associated macrophages (TAMs) subsequently. Particularly, it illustrated great therapeutic effects which derived from functional conversion of macrophages. Our strategy was to design a microenvironment-responsive material for local macrophage reverse modification which could overcome the physiological barrier of solid tumor. The shifting of macrophages by IL-12⊂P1 realized immunomodulation in microenvironment for cancer therapy with negligible cytotoxicity. We expected that regulating the function of TAMs by pH-responsive nanomaterials would be a promising therapeutic approach for cancer immunotherapy.



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