期刊
ACS NANO
卷 14, 期 10, 页码 13894-13904出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c06290
关键词
macrophage; remote-controlled self-destruction; oxygen generation; glutathione depletion; synergistic therapy
类别
资金
- Natioanl Key R&D Program of China [2019YFA0709202]
- Natural Science Foundation of China [21533008, 91856205, 21871249, 21820102009]
- Key Program of Frontier of Sciences [CAS QYZDJ-SSW-SLH052]
Macrophages are known to penetrate tumor central hypoxic areas and hold great potential in cancer drug delivery. However, it remains a big challenge for current macrophage-based drug delivery systems (MDDSs) to prevent premature drug leakage and sufficiently release the therapeutics in tumor sites. Moreover, these MDDSs would encounter drug resistance and a hypoxic microenvironment in solid tumors, which further compromised their therapeutic efficacy. Herein, by internalizing a smart nanoparticle (doxorubicin (DOX)-loaded mesoporous carbon nanosphere wrapped with MnO2 shell) into macrophages, a macrophage vehicle (MMDM) is developed for enhanced chemo/chemodynamic synergistic therapy. The resulting MMDM could avoid premature drug leakage-induced cell dysfunction and maximally maintain cell viability. After accumulating in tumor tissues, the MMDM could be destroyed under a near-infrared laser to sufficiently release the nanoparticle out of the carrier macrophages. The released nanoparticle could then decompose H2O2 to generate O-2 in the tumor microenvironment to relieve tumor hypoxia. Meanwhile, the MnO2 shell of the nanoparticle is reduced to Mn2+ by intracellular glutathione, triggering the release of DOX and subsequently resulting in an enhanced Mn2+-mediated Fenton-like reaction. This study provides an intriguing strategy to macrophage-based delivery systems for enhanced chemo/chemodynamic synergistic therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据