A novel strategy based on a ligand-switchable nanoparticle delivery system for deep tumor penetration
A novel strategy based on a ligand-switchable nanoparticle delivery system for deep tumor penetration
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基于配体可切换纳米颗粒递送系统的新策略用于深部肿瘤穿透
DOI：
10.1039/c8nh00415c
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发表时间：
2019-05-01
影响因子：
9.7
通讯作者：
Shi, Linqi
中科院分区：
文献类型：
--
作者：
Ding, Yuxun;Liu, Jinjian;Shi, Linqi
许多纳米药物的肿瘤渗透性差，严重限制了它们的治疗效率。尽管细胞穿透肽（CPP）的组合已被报道为改善纳米颗粒的穿透能力的有前景的策略，但CPP的非特异性相互作用可能减少纳米颗粒的循环时间并增加其副作用，使其在许多体内环境中不适用。在此，我们报告了一种配体可转换的策略，以抑制CPP在血流中的非特异性相互作用，并在进入肿瘤部位时快速重新激活其功能。由于PAE的快速相变，CPP可以完全隐藏在血浆中的PEG冠下，避免与免疫细胞和正常组织直接相互作用。一旦发生血管外渗，酸性肿瘤微环境将触发CPP暴露，促进抗肿瘤药物扩散到肿瘤部位深处。由于这种配体可转换的性质，纳米载体能够同时实现长时间的循环、优先积累和有效的肿瘤穿透，从而产生高抗肿瘤活性和低不良反应，并且还提供了使CPP以及其他非特异性配体能够在体内应用的通用方法。
The poor tumor penetration of many nanomedicines severely limits their therapeutic efficiency. Although the combination of cell-penetrating peptides (CPPs) has been reported as a promising strategy to improve the penetration capability of nanoparticles, the nonspecific interactions of CPPs may reduce nanoparticles' circulation time and increase their side effects, making them inapplicable in many in vivo settings. Herein, we report a ligand-switchable strategy to inhibit CPPs' nonspecific interactions in the bloodstream and quickly reactivate their functions when entering into tumor sites. Due to the rapid phase transition of PAE, the CPPs can be completely hidden under the PEG corona in plasma, avoiding direct interaction with the immune cells and normal tissues. Once extravasation from blood vessels occurs, the acidic tumor microenvironment would trigger the exposure of the CPPs, promoting the diffusion of antitumor agents deep into the tumor sites. With this ligand-switchable property, nanocarriers are capable of achieving long durations of circulation, preferential accumulation and efficient tumor penetration simultaneously, giving rise to high antitumor activity and low adverse reactions, and also providing a universal approach to enable in vivo applications of CPPs as well as other nonspecific ligands.