体内
药物输送
单核吞噬细胞系统
免疫系统
PEG比率
渗透(HVAC)
紫杉醇
马来酰亚胺
巨噬细胞
材料科学
化学
生物物理学
体外
药理学
癌症研究
免疫学
医学
生物化学
纳米技术
化疗
生物
内科学
生物技术
财务
经济
复合材料
高分子化学
作者
Xin Wang,Xiandi Meng,Kuirong Mao,Hongmei Chen,Xiuxiu Cong,Feiqi Liu,Jialiang Wang,Shuhan Liu,Yanbao Xin,Ge Zhu,Huizhu Tan,Yong‐Guang Yang,Tianmeng Sun
出处
期刊:Biomaterials
[Elsevier]
日期:2023-05-31
卷期号:300: 122187-122187
被引量:10
标识
DOI:10.1016/j.biomaterials.2023.122187
摘要
Radiotherapy (IR) is capable of enhancing antitumor immune responses. However, IR treatment also aggravates the infiltration of peripheral macrophages into the tumor, resulting in reversing the therapeutic effects of antitumor immunity. Thus, a strategy to effectively prevent tumor infiltration by macrophages may further improved the therapeutic efficacy of radiotherapy. Herein, we found that PEGylated solid lipid nanoparticles with maleimide as PEG end-group (SLN-PEG-Mal) show significantly enhanced adsorption onto RBCs through reacting with reactive sulfhydryl groups on RBCs' surface both in vitro and in vivo, and caused significant changes in the surface properties and morphology of RBCs. These RBCs adsorbed by SLN-PEG-Mal were rapidly removed from circulation due to efficient engulfment by reticuloendothelial macrophages, supporting the usefulness of SLN-PEG-Mal for macrophage-targeted drug delivery. While lacking the use of radioisotope tracing (considered the gold standard for PK/BD studies), our data align with the expected pathway of host defense activation through surface-loaded RBCs. Importantly, injection of paclitaxel-loaded SLN-PEG-Mal effectively inhibited the tumor-infiltration by macrophages, and significantly improved the antitumor immune responses in tumor-bearing mice treated with low-dose irradiation. This study provides insights into the effects of maleimide as PEG end-group on enhancing the interaction between PEGylated nanoparticles and RBCs and offers an effective strategy to inhibit tumor infiltration by circulating macrophages.
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