pH-Responsive charge switchable PEGylated ε-poly-l-lysine polymeric nanoparticles-assisted combination therapy for improving breast cancer treatment

• Published in: Journal of controlled release 2020-10, Vol.326, p.350-364
• Main Authors: Guo, Zhihao, Sui, Junhui, Ma, Mengcheng, Hu, Jianshe, Sun, Yong, Yang, Liqun, Fan, Yujiang, Zhang, Xingdong
• Format: Article
• Language: English
• Subjects: Charge switch; Combination therapy; Dual-pH responsive; Polymeric nanoparticles; ε-Poly-l-lysine
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2020.07.030

Stimuli-responsive nanotechnology-mediated drug co-delivery system is a notable strategy to improve access of the systemically administered chemotherapeutics to the tumors. Herein, a tailor-made 2,3-dimethylmaleic-anhydride-poly(ethylene glycol)-ε-poly-l-lysine-doxorubicin /lapatinib polymeric nanoplatform (DMMA-P-DOX/LAP) for synergistically eliminating breast cancer is developed by encapsulating lapatinib into dual-pH responsive charge switchable biopolymer-doxorubicin conjugate nanoparticles. The physicochemical properties of polymeric nanoparticles are conducive to their stable circulation in the physiological condition, but reverse the surface charge from negative to positive ultrasensitively in slightly acidic tumor microenvironment, facilitating cell internalization and deep tumor penetration. Subsequently, DOX and LAP are synchronously released into the cytoplasm in response to the significantly increased acidity of intracellular environment. As a result, the combination therapy by DMMA-P-DOX/LAP nanoparticles compels the solid tumors to contract significantly or even vanish completely in the MCF-7 tumor model, moreover, the structural composition with amino acid and bioinert PEG ensures the favorable biosecurity of the co-delivery system in vivo. This dual-pH responsive nanotechnology-mediated drug co-delivery system provides great potentials for safe and effective cancer therapy. [Display omitted] •Charge switchable nanoparticles (NPs) were prepared through a green method.•Enhanced penetration and cellular uptake of NPs was realized by charge reverse.•Co-delivery of doxorubicin and lapatinib exhibited synergistic anticancer activity.•The NPs compelled MCF-7 solid tumors to contract significantly or even vanish.•The NPs relieved the side effects and presented excellent biosecurity.