Journal
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 82, Issue -, Pages 60-68Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.msec.2017.08.063
Keywords
Paclitaxel; pH-responsive; Prodrug; Polymeric nanoparticles
Categories
Funding
- NSFC [21474115, 51573195, 81630056, 21674120]
- MOST [2014CB932200]
- Young Thousand Talents Program
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Endosomal pH-responsive micellar nanoparticles were prepared by self-assembly of an amphiphilic poly(ethylene glycol)-acetal-paclitaxel (PEG-acetal-PTX) prodrug, and free PTX could be encapsulated in the hydrophobic core of the nanoparticles. These nanoparticles exhibited excellent storage stability for over 6 months under normal conditions, but disassembled quickly in response to faintly acidic environment. Incorporating physical encapsulation and chemical conjugation, the PTX concentration in the nanoparticles solution could reach as high as 3665 mu g/mL, accompanying with a high drug loading capacity of 60.3%. Additionally, benefitting from the difference in drug release mechanism and rate between encapsulated PTX and conjugated PTX, a programmed drug release behavior was observed, which may result in higher intracellular drug concentration and longer action time. CCK-8 assays showed that the nanoparticles demonstrated superior antittimor activity than free PTX against both HeLa and MDA-MB-231 cells. These prodrug-based nanomedicines have a great potential in developing translational PTX formulations for cancer therapy.
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