1. pH-sensitive polymeric nanoparticles of mPEG-PLGA-PGlu with hybrid core for simultaneous encapsulation of curcumin and doxorubicin to kill the heterogeneous tumour cells in breast cancer.
- Author
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Yuan JD, ZhuGe DL, Tong MQ, Lin MT, Xu XF, Tang X, Zhao YZ, and Xu HL
- Subjects
- Animals, Capsules, Cell Proliferation drug effects, Drug Carriers chemistry, Drug Liberation, Humans, Hydrogen-Ion Concentration, MCF-7 Cells, Mice, Particle Size, Polyglutamic Acid chemistry, Xenograft Model Antitumor Assays, Breast Neoplasms pathology, Curcumin chemistry, Curcumin pharmacology, Doxorubicin chemistry, Doxorubicin pharmacology, Nanoparticles chemistry, Polyesters chemistry, Polyethylene Glycols chemistry, Polyglutamic Acid analogs & derivatives
- Abstract
Most breast tumours are heterogeneous and not only contain the bulk of differentiated tumour cells but also a small population of highly tumorigenic and intrinsically drug-resistant cancer stem cells (CSCs). Herein, a pH-sensitive nanoparticle with simultaneous encapsulation of curcumin and doxorubicin (CURDOX-NPs) was prepared by using monomethoxy (polyethylene glycol)-b-P (D,L-lactic-co-glycolic acid)-b-P (L-glutamic acid) polymer to simultaneously target the differentiated tumor cells and CSCs. CURDOX-NPs had a mean diameter of 107.5 nm and zeta potential of -13.7 mV, determined by DLS. Drug-loading efficiency for curcumin and doxorubicin was reaching to 80.30% and 96.2%, respectively. Moreover, a cascade sustained-release profiles with the faster release of CUR followed by a slower release of DOX was observed in normal pH7.4 condition. Moreover, a pH-sensitive release profile for each cargo was seen in pH5.0 condition. The anti-tumour effect of CURDOX-NPs on CSCs-enriching MCF-7/ADR mammospheres was confirmed by in vitro. Moreover, a significant regression of tumour growth after treatment with CURDOX-NPs was also observed in Xenograft mice model. The percentage of CSCs in tumour significantly decreased from 39.9% in control group to 6.82% after treatment with CURDOX-NPs. The combinational delivery of CUR and DOX may a potentially useful therapeutic strategy for refractory breast cancer.
- Published
- 2018
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