Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pharmacy, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan 430030, China.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China; National Engineering Research Centre for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430030, China.
J Control Release. 2017 Jul 28;258:108-120. doi: 10.1016/j.jconrel.2017.05.016. Epub 2017 May 15.
Conventional tumor starving therapy by reducing its vessel density may be effective at early treatment but potentially contributes to tumor hypoxia, drug resistance and metastasis. A new strategy through enhancing tumor angiogenesis in combination with effective chemotherapeutic drugs, has shown successful tumor growth and spread inhibition. To achieve in situ release of angiogenic and antitumor drugs in tumor, we designed a precise ratiometric polymeric hybrid micelle system for co-delivering nitric oxide and paclitaxel. The hybrid micelles could accumulate in tumor via the long blood circulation and enhanced permeability and retention (EPR) effect, promote the drug accumulation and penetration in tumor by in situ increased vascular permeability, blood perfusion and vessel density, achieve the synergistic antitumor effect of nitric oxide and paclitaxel through modified tumor microenvironment, overcome multidrug resistance and inhibit metastasis. This study presents a combinational therapy against tumor progression and spread, which shows great potential in cancer therapy of the future.
传统的肿瘤饥饿疗法通过降低其血管密度可能在早期治疗中有效，但可能导致肿瘤缺氧、耐药性和转移。一种新的策略是通过增强肿瘤血管生成并结合有效的化疗药物，已显示出成功抑制肿瘤生长和扩散。为了在肿瘤中实现血管生成和抗肿瘤药物的原位释放，我们设计了一种精确的比例聚合物杂化胶束系统，用于共递送一氧化氮和紫杉醇。该杂化胶束可以通过长循环和增强的通透性和保留（EPR）效应在肿瘤中积累，通过原位增加血管通透性、血液灌注和血管密度促进药物在肿瘤中的积累和渗透，通过改变肿瘤微环境实现一氧化氮和紫杉醇的协同抗肿瘤作用，克服多药耐药性并抑制转移。这项研究提出了一种针对肿瘤进展和扩散的联合治疗方法，在未来的癌症治疗中具有很大的潜力。
