10.6084/m9.figshare.5759397.v1 Jian-Dong Yuan Jian-Dong Yuan De-Li ZhuGe De-Li ZhuGe Meng-Qi Tong Meng-Qi Tong Meng-Ting Lin Meng-Ting Lin Xia-Fang Xu Xia-Fang Xu Xing Tang Xing Tang Ying-Zheng Zhao Ying-Zheng Zhao He-Lin Xu He-Lin Xu 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 Taylor & Francis Group 2018 Curcumin doxorubicin block copolymer nanoparticles poly(L-glutamic acid) poly(D,L-lactic-co-glycolic acid) multi-drugs resistance 2018-01-05 07:07:54 Journal contribution https://tandf.figshare.com/articles/journal_contribution/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/5759397 <p>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 <i>in vitro</i>. 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.</p>