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

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.

Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy

“…To date, several NP formulations, such asmPEG-PCL micelles [79], poly(alkyl cyanoacrylate) NPs [80] and PLLA NPs [81], have been obtained for the co-delivery of DOX and CUR, although the majority of these NPs release the drug non-specifically, with a slow degradation of the polymeric micelles. Co-encapsulation of DOX and CUR in pH-sensitive NPs has been shown as a good strategy in treating cancer in a synergistic manner with increased efficacy and lower toxicity by off-target exposure.The new synthesized triblock copolymer monomethoxy (polyethylene glycol)-b-poly(D,L-lactic-co-glycolic acid)-b-poly(L-glutamic acid) (mPEG-PLGA-PGlu), including two hydrophobic polymers, PGlu and PLGA, and the modified hydrophilic mPEG polymer, confirmed possible encapsulation of CUR and DOX, with simultaneous targeting of heterogeneous breast cancer cells (Table 1) [54]. These NPs are pH sensitive, and the PGlu segment incorporates DOX through electrostatic interactions that alter the configuration in response to endosomal pH, while PLGA encapsulates CUR inside the core through hydrophobic interactions.…”

Curcumin on the “flying carpets” to modulate different signal transduction cascades in cancers: Next‐generation approach to bridge translational gaps

“…23 Mammosphere-derived CD44 high /CD24 low MCF-7/ADR cancer stem cells were efficiently targeted by CURDOX-NPs. 23 Both miR-770-5p and miR-1247 were noted to be upregulated in the curcumin-treated prostate cancer stem cells (PCSCs). Proliferation rate of miR-770-5p and miR-1247overexpressing PCSCs was notably reduced.…”

Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects

“…The use of nanocarriers in the treatment of this type of cancer opens a door to improve their effectiveness. Yuan et al [ 144 ] studied the action of pH-sensitive PEG–PLGA–PGlu (polyglutamic acid) NP embedded with curcumin and doxorubicin in drug resistant cancer stem cells and tumor cells of breast tumors, obtaining good results in mice models. The combination of the use of nanoparticulate systems with photodynamic therapy in breast cancer were investigated by Hu et al [ 145 ].…”