期刊
ACS APPLIED MATERIALS & INTERFACES
卷 5, 期 8, 页码 3108-3117出版社
AMER CHEMICAL SOC
DOI: 10.1021/am400017q
关键词
cross-linked micelles; pH sensitive; intracellular drug delivery; poly(ethylene glycol)-hyperbranched poly(beta-aminoester)s; doxorubicin; real-time in situ fluorescence microscopy
资金
- NSERC
- NSERC RTI Grant, Manitoba
- Institute of Child Health
- China 863 Project [2012AA020504]
- National Basic Research Program of China [2012CB619100]
Cross-linked polymeric micelles have gained increasing research interest in the past decade due to the instability of existing polymeric micelles when used in vivo. In this study, we reported a series of covalently cross-linked pH-sensitive biodegradable micelles based on the poly(ethylene glycol)-hyperbranched poly(beta-aminoester)s with acrylate group terminals (PEG-HBPAE-A) copolymers for intracellular delivery of doxorubicin (DOX). PEG-HBPAE-A can be self-assembled to form micellar nanoparticles in aqueous solution with diameters of approximately 160 nm. The non-cross-linked micelles (NCLMs) were cross-linked upon UV irradiation to form cross-linked micelles (CLMs). H-1 NMR, FT-IR and dynamic light scattering (DLS) were utilized to investigate the process of the UV cross-linking and the. stability of CLMs. The results showed the significantly enhanced stability for CLMs in comparison to NCLMs. pH sensitivity of CLMs and NCLMs were also estimated by DLS. In vitro drug release studies confirmed that DOX release from DOX-loaded CLMs was greatly inhibited upon the neutral pH environment, whereas DOX underwent faster release in acidic conditions. MTT assays showed that DOX-loaded micelles had a similar inhibition rate for HepG-2 and MCF-7 cell lines compared with free DOX, whereas the blank CLMs and NCLMs showed very low c-ytotoxicity. Laser scanning confocal microscopy and real-time in situ fluorescence microscopy were exploited to investigate drug uptake in cells and drug distribution in the interior of cells. These results showed a promising nanocarrier for intracellular DOX delivery with great potential for cancer therapy.
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