自组装生物纳米材料调控肿瘤基质微环境的新策略

构建了两种基于自组装生物纳米材料对肿瘤基质微环境调控的肿瘤综合治疗方案，实现了抗肿瘤以及抑制肿瘤转移的效果。其中一种自组装纳米材料是一种MMP2酶响应性级联递送纳米载体，基于甲氧基聚（乙二醇）-聚（D，l-乳酸-共甘醇）（mPEG-PLGA）纳米颗粒封装在肽杂交脂质体中，共同传递LOXL2和DDR1抑制剂（LOXL2-DDR1 @MLP），另一种自组装纳米材料是将CXCL12沉默siRNA装载进基于细胞穿透肽(CPP，9-精氨酸（R9））的自组装纳米颗粒，表面吸附抗FAP-α单抗形成传递系统（PNP/siCXCL12/ mAb）。对于LOXL2-DDR1 @MLP，利用电子显微镜等手段表征了其形貌、粒径分布、表面电荷等关键纳米特性；对于PNP/siCXCL12/ mAb，通过电泳迁移率试验评估，siCXCL12被成功包载。验证了自组装纳米颗粒对肿瘤基质成分及微环境的调控作用。在小鼠模型中评估了自组装纳米颗粒促进药物渗透的能力和抑制肿瘤转移的疗效。Two comprehensive tumor therapeutic regimens for regulating tumor stromal microenvironment based on self-assembled biological nanomaterials were developed, achieving both anti-tumor and anti-metastasis effects. One of the self-assembled nanomaterials is an MMP2-responsive cascade delivery nanocarrier, which encapsulates methoxy poly(ethylene glycol)-poly(D,L-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles into peptide-hybrid liposomes to co-deliver LOXL2 and DDR1 inhibitors (LOXL2-DDR1 @MLP). The other self-assembled nanomaterial loads CXCL12-silencing siRNA into self-assembled nanoparticles based on cell-penetrating peptides (CPP, 9-arginine (R9)), and adsorbs anti-FAP-α monoclonal antibodies on the surface to form the delivery system (PNP/siCXCL12/ mAb). For LOXL2-DDR1 @MLP, key nanoscale properties including morphology, particle size distribution and surface charge were characterized via electron microscopy and other characterization methods. For PNP/siCXCL12/ mAb, successful encapsulation of siCXCL12 was verified through electrophoretic mobility assay. The regulatory effects of the self-assembled nanoparticles on tumor stromal components and microenvironment were validated. The capacity of the self-assembled nanoparticles to promote drug penetration and their therapeutic efficacy against tumor metastasis were evaluated in mouse models.

搜集汇总

背景与挑战

背景概述

该数据集聚焦于自组装生物纳米材料在调控肿瘤基质微环境中的应用，构建了两种新型纳米材料系统，旨在通过靶向递送抑制剂或沉默基因来增强抗肿瘤疗效并抑制肿瘤转移。研究包括纳米材料的表征、微环境调控作用的验证，以及在小鼠模型中评估其药物渗透能力和治疗效果。