State Key Laboratory and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University , No. 17, Section 3, Southern Renmin Road, Chengdu, Sichuan, P. R. China.
School of Pharmacy, Chengdu Medical College , No. 783, Xindu Avenue, Xindu District, Chengdu, Sichuan, China.
ACS Appl Mater Interfaces. 2017 Dec 27;9(51):44410-44422. doi: 10.1021/acsami.7b17022. Epub 2017 Dec 14.
Because of the nontargeting release of anticancer drugs, conventional chemotherapy results in serious side effects and poor therapeutic outcomes. In addition, hypoxia situation in the tumor microenvironment also promotes the growth and metastasis of tumors. Multifunctional nanocarriers with stimuli-activation and hypoxia-relieving properties can help overcome some of these limitations. In this study, we have constructed a nanocarrier which is named PBMn-DOX@RBC. A Prussian blue/manganese dioxide (PBMn) nanoparticle is used as an oxygen precursor or catalyzer for HO activation, and a red blood cell (RBC) membrane is used to increase the loading capacity of doxorubicin (DOX) and prolong the circulation time in vivo. HO is overproduced in tumor tissues and tumor cells. It can be used as a stimulus to activate drug release. In the presence of HO, the hypoxia inside the tumors is relieved by the administration of PBMn-DOX@RBC. The generated oxygen disrupts the RBC coated on the surface of PBMn, which accelerates the release of DOX. RBCs also prolong the circulation time of the nanometer system in vivo. By combining the photothermal therapy (PTT) and chemotherapy, the tumor growth inhibition mediated by PBMn-DOX@RBC is further enhanced. PBMn-DOX@RBC fulfills the demands to relieve tumor hypoxia and enhance cancer chemotherapy/PTT.
由于抗癌药物的非靶向释放，传统化疗会导致严重的副作用和较差的治疗效果。此外，肿瘤微环境中的缺氧情况也会促进肿瘤的生长和转移。具有刺激激活和缓解缺氧特性的多功能纳米载体可以帮助克服其中的一些限制。在本研究中，我们构建了一种纳米载体，命名为 PBMn-DOX@RBC。普鲁士蓝/二氧化锰（PBMn）纳米颗粒可用作 HO 激活的氧前体或催化剂，红细胞（RBC）膜用于增加阿霉素（DOX）的载药量并延长体内循环时间。HO 在肿瘤组织和肿瘤细胞中过度产生。它可以用作刺激物来激活药物释放。在 HO 的存在下，通过施用 PBMn-DOX@RBC 来缓解肿瘤内部的缺氧。产生的氧气会破坏表面涂有 RBC 的 PBMn，从而加速 DOX 的释放。RBC 还延长了纳米系统在体内的循环时间。通过结合光热治疗（PTT）和化学疗法，进一步增强了由 PBMn-DOX@RBC 介导的肿瘤生长抑制作用。PBMn-DOX@RBC 满足缓解肿瘤缺氧和增强癌症化疗/PTT 的需求。
