A carbohydrate mimetic peptide modified size-shrinkable micelle nanocluster for anti-tumor targeting and penetrating drug delivery
A carbohydrate mimetic peptide modified size-shrinkable micelle nanocluster for anti-tumor targeting and penetrating drug delivery
复制标题
一种碳水化合物模拟肽修饰的尺寸可收缩的胶束纳米簇，用于抗肿瘤靶向和渗透药物输送
DOI：
10.2147/ijn.s213455
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Li, Jinming
中科院分区：
文献类型：
--
作者：
Chen, Qinyue;Liang, Huihui;Li, Jinming
目的通过纳米粒给药化疗药物时，给药系统应首先在肿瘤部位聚集，然后通过肿瘤组织进入内部。通过受体-配体结合介导的特异性肿瘤靶向途径可以实现纳米颗粒的理想聚集，并且需要较小尺寸的纳米颗粒才能穿透。方法和材料我们构建了一种基于pH敏感框架的肿瘤靶向基序IF-7修饰的尺寸可收缩纳米簇（IF-7-MNC），其可以在酸性环境中崩解以释放聚集在内部的胶束。胶束由两亲性嵌段共聚物PEG-PLA构建以包封紫杉醇（PTX），而由TPGS-PEI组成的交联框架用作聚集和释放胶束的网。这种纳米平台可以通过配体IF-7与肿瘤受体Annexin A1特异性结合，然后收缩成具有所需尺寸的小胶束用于渗透。结论112.27±6.81 nm的IF-7-MNC在0.01 M，pH5.0的PBS中可收缩成14.89±0.32 nm的胶束。细胞摄取结果显示，IF-7-MNC可被A549细胞和HUVEC细胞显著内化，而与MNC相比，IF-7-MNC可更显著地渗透到三维肿瘤球体中。生物分布结果显示，24小时时肿瘤部位中IF-7-MNC的荧光比MNC强4.5倍。抗肿瘤生长实验结果表明，IF-7-MNC比MNC更有利于肿瘤的治疗，其中载PTX的IF-7-MNC（IF-7-PMNC）治疗组的肿瘤生长抑制率为88.29%，显著高于PMNC治疗组（p<0.05）。
Purpose To deliver the chemotherapeutics through the nanoparticles, the delivery system should accumulate at the tumor site first and then penetrate through the interstitium into the interior. The specific tumor-targeting pathway mediated via the receptor-ligand binding could achieve the desirable accumulation of nanoparticles, and the nanoparticles with smaller sizes were required for penetration. Methods and materials We constructed a size-shrinkable nanocluster modified with a tumor-targeting motif IF-7 (IF-7-MNC) based on a pH-sensitive framework which could be disintegrated in an acid environment to release the micelles aggregated inside. The micelles were constructed by amphiphilic block copolymers PEG−PLA to encapsulate paclitaxel (PTX), while the cross-linked framework consisting of TPGS-PEI was used as a net to gather and release micelles. This nanoplatform could specifically bind with the tumor receptor Annexin A1 through the ligand IF-7 and then shrunk into small micelles with a desirable size for penetration. Conclusion IF-7-MNC of 112.27±6.81 nm could shrink into micelles in PBS (0.01 M, pH 5.0) with sizes of 14.89±0.32 nm. The cellular-uptake results showed that IF-7-MNC could be significantly internalized by A549 cells and HUVEC cells, while the penetration of IF-7-MNC could be more prominent into the 3D-tumor spheroids compared with that of MNC. The biodistribution results displayed that the fluorescence of IF-7-MNC in the tumor site at 24 hrs was 4.5-fold stronger than that of MNC. The results of anti-tumor growth demonstrated that IF-7-MNC was more favorable for the tumor therapy than MNC, where the inhibitory rate of tumor growth was 88.29% in the PTX-loaded IF-7-MNC (IF-7-PMNC) treated group, significantly greater than PMNC treatment group (p<0.05).