期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 22, 页码 18560-18573出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b04394
关键词
injectable hydrogel; nanohydrogel; stimuli-responsive; localized drug delivery; combination therapy
资金
- National Key Research and Development Program of China [2017YFA0205302]
- National Natural Science Foundation of China Program [21404058]
- Natural Science Foundation of Jiangsu Province [BK20140864]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT_15R37]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), NUPTSF [NY218029]
- Postdoctoral Science Foundation of China [2014M561697]
- State Key Laboratory of Analytical Chemistry for Life Science [5431ZZXM1717]
Drug combination therapies employing dual-drug delivery systems offer an effective approach to reduce disadvantages of single-drug therapy, such as high dose and easy generation of drug resistance. Herein, a dual-drug delivery system based on nanogel-incorporated injectable hydrogel (NHG) was designed for sequential local delivery of combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) for anti-angiogenesis and anticancer combination therapy. The injectable hydrogel was prepared for loading and quick release of hydrophilic drug CA4P, while the pH and redox stimuli-responsive nanohydrogels were incorporated into the injectable hydrogel by pH-responsive boronate ester bond for sustained long-term DOX delivery. The dual-drug-loaded NHG system released CA4P and DOX sequentially and exhibited high inhibitory activities on the cancer cell proliferation in vitro. It displayed superior therapeutic efficacy in vivo with only one single injection. Immunohistochemistry analyses suggested a synergistic therapeutic effect through tumor vascular collapse caused by CA4P and tumor cell apoptosis induced by DOX. The combination therapy of antiangiogenic and cytotoxic drugs using NHG delivery system offers a promising approach for improved cancer therapeutic efficacy. The nanogel-embedded injectable hydrogel can be employed as a universal drug carrier for local dual-drug delivery with sequential release behaviors by simple injection.
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