期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 14, 期 -, 页码 2233-2251出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S195900
关键词
combination therapy; glucose oxidase; hyaluronic acid; pH-sensitivity; nanomedicine
资金
- National Natural Science Foundation of China [81373363]
- Key New Drug Innovation Project from the Ministry of Science and Technology of the People's Republic of China [2009ZX09310-004]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2015ZX09501001]
- Postgraduate Research and Innovation Plan Project in Jiangsu Province [KYLX16_1178]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
Background: The combination of novel starving therapy with chemotherapy is one of the most promising strategies to achieve an effective antitumor activity. Methods: Herein, we developed a multifunctional mesoporous silica nanoparticle (MSNs-GOx/PLL/HA) coated with poly (L-lysine) (PLL) and hyaluronic acid (HA) for co-delivery of glucose oxidase (GOx) and anticancer drug paclitaxel (PTX) for cancer treatment for the first time. Compared to single chemotherapy, introduction of GOx would not only selectively trigger the consumption of intracellular glucose, leading to the interruption of energy supply, but also elevat the endogenous H2O2 level, inducing stronger therapeutic effects. Results: The novel drug delivery system possessed desirable particle diameter of 40 nm and exhibited a pH-sensitive drug release behavior. An in vitro cellular uptake study indicated that MSNs-GOx/PLL/HA nanoparticles effectively enhanced the cellular uptake of drug in an apparently CD44 receptor-dependent manner, and delivered more cargo into cytoplasm via endolysosomal escape effect in presence of PLL. The nanoplatform has also demonstrated amplified synergistic therapeutic effects for remarkable tumor inhibition in a xenograft animal tumor model. Conclusion: Consequently, the developed synergistic starving-like/chemotherapy may provide a potential platform for next generation cancer therapy.
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