ZIF ‐8‐Encapsulated Pexidartinib Delivery via Targeted Peptide‐Modified M1 Macrophages Attenuates MDSC‐Mediated Immunosuppression in Osteosarcoma
This study proposes a strategy for ZIF-8-encapsulated pexidartinib delivery via targeted peptide-modified M1 macrophages. Modified macrophages not only have a stronger affinity for tumors but also carry anti-tumor drugs that can act precisely on tumor sites. Through this therapeutic strategy, M1 macrophages achieve a precise, sustained, and improved anti-tumor effect. AbstractAdoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell funct...
Source: Small - Category: Nanotechnology Authors: Jiabao Dong,
Xupeng Chai,
Yucheng Xue,
Shiyun Shen,
Zhuo Chen,
Zetao Wang,
Eloy Yinwang,
Shengdong Wang,
Liang Chen,
Fengfeng Wu,
Hengyuan Li,
Zehao Chen,
Jianbin Xu,
Zhaoming Ye,
Xiongfeng Li,
Qian Lu Tags: Research Article Source Type: research