Journal
EUROPEAN POLYMER JOURNAL
Volume 117, Issue -, Pages 372-381Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.eurpolymj.2019.04.050
Keywords
10-HCPT; pH/enzyme-sensitivity; Prodrug nanoparticles; Controlled release
Categories
Funding
- National Natural Science Foundation of China [51373130, 21476179, 51473130, 51303145]
- National Training Programs of Innovation and Entrepreneurship for Undergraduates [201810497005]
- one hundred talents project of Guangzhou University [69-18ZX10016]
- 2016 Wuhan Yellow Crane Talents (Science) Program
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For enhanced stability and anticancer efficacy, the 10-Hydroxycamptothecin (10-HCPT) structure based pH/enzyme responsive polymeric prodrug nanoparticles were constructed by conjugating 10-HCPT to carboxymethylchitosan (CMCS) via pH/enzyme sensitive succinyl linkage followed by ultrasonic dispersion. At pH 7.4 the nanoparticles exhibited a core-shell structure and good in vitro stability with very little drug release. However, upon exposure to pH 5.0, the nanoparticles showed nanogel-like morphology, accompanied by a cumulative drug release rate of up to 71.4% in 60 h in the presence of 2 mu M papain, which was nearly two times as much as that in the case of 0.2 mu M papain, indicating that enzyme and pH dual-stimulation can significantly elevate tumor cell-selective drug release. In comparison with IC50 of free 10-HCPT, HCPT-g-CMCS nanoparticles exhibited about 4.5 times increase in cytotoxicity on 4T1 cancer cells, while an obviously reduced cell inhibition was observed for healthy liver cell line L-O2. Furthermore, in vitro cell studies confirmed the enhanced intracellular drug release of the system in the 4T1 cancer cells. Hence, the pH/enzyme-sensitive prodrug nano particles based on HCPT-g-CMCS may be a promising nano-drug delivery system for cancer therapy.
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