Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 16, Pages 13939-13949Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b02281
Keywords
reduction-response; polyphosphoestqs; prodrug; Michael addition polymerization; click reaction
Funding
- National Natural Science Foundation of China [21374066]
- Major Program of the Natural Science Project of Jiangsu Higher Education Institutions [15KJA150007]
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
- Soochow-Waterloo University Joint Project for Nanotechnology from Suzhou Industrial Park
Ask authors/readers for more resources
Polyphosphoesters (PPEs), as potential candidates for biocompatible and biodegradable polymers, play an important role in material science. Various synthetic methods have been employed in the preparation of PPEs Such as polycondensation, polyaddition, ring opening polymerization, and olefin metathesis polymerization. In this study, a.series of linear PPEs has been prepared via one-step Michael addition polymerization. Subsequently, camptothecin (CPT) derivatives containing disulfide bonds and azidb groups were linked onto the side chain of the PPE through Cu(I)-catalyzed azidealkyne cyclo-addition click chemistry to yield :a reduction-responsive polymeric prodrug P(EAEP-PPA)-g-ss-CPT. The chemical structures were characterized by nuclear magnetic resonance spectroscopy, gel permeation.chromatography, Fourier transform infrared, ultraviolet visible spectrophotometer, and high performance liquidchromatograph analyses, respectively. The amphiphilic prodrug could self-assemble into micelles in aqueous solution. The average particle,size and morphology of the pro drug micelles were measured by dynamic light scattering and transmission electron microscopy, respectively. The results of size change under different conditions indicate that the micelles possess a favorable stability in physiological conditions and can be degraded in reductive medium. Moreover, the studies of in vitro drug release behavior,confirm the reduction-responsive degradation of the prodrug micelles. A methyl thiazolyl tetrazolium assay verifies the good biocompatibility of P(EAEP-PPA) not only for normal cells, but also for tumor cells. The results of cytotoxicity and the intracellular uptake about prodrug micelles further demonstrate that the prodrug micelles can efficiently release CPT into 4T1 or HepG2 cells to inhibit the cell proliferation. All these results show that the polyphosphoester based prodrug can be used for triggered drug delivery system in cancer treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available