The evolving dynamics of drug resistance due to tumor heterogeneity often creates impediments to traditional therapies making it a challenging issue for cancer cure.Breast cancer often faces challenges of current ther...The evolving dynamics of drug resistance due to tumor heterogeneity often creates impediments to traditional therapies making it a challenging issue for cancer cure.Breast cancer often faces challenges of current therapeutic interventions owing to its multiple complexities and high drug resistivity,for example against drugs like trastuzumab and tamoxifen.Drug resistance in the majority of breast cancer is often aided by the overtly expressed P-glycoprotein(P-gp)that guides in the rapid drug efflux of chemotherapy drugs.Despite continuous endeavors and ground-breaking achievements in the pursuit of finding better cancer therapeutic avenues,drug resistance is still a menace to hold back.Among newer therapeutic approaches,the application of phytonutrients such as alkaloids to suppress P-gp activity in drug-resistant cancers has found an exciting niche in the arena of alternative cancer therapies.In this work,we would like to present a black pepper alkaloid derivative known as Bio Perine-loaded chitosan(CS)-polyethylene glycol(PEG)coated polylactic acid(PLA)hybrid polymeric nanoparticle to improve the bioavailability of Bio Perine and its therapeutic efficacy in suppressing P-gp expression in MDA-MB 453 breast cancer cell line.Our findings revealed that the CS-PEG-Bio PerinePLA nanoparticles demonstrated a smooth spherical morphology with an average size of316 nm,with improved aqueous solubility,and provided sustained Bio Perine release.The nanoparticles also enhanced in vitro cytotoxicity and downregulation of P-gp expression in MDA-MB 453 cells compared to the commercial inhibitor verapamil hydrochloride,thus promising a piece of exciting evidence for the development of Bio Perine based nano-drug delivery system in combination with traditional therapies as a crucial approach to tackling multi-drug resistance in cancers.展开更多
基金the Ministry of Education,Culture,Sports,Science and Technology(MEXT),JapanInoue Enryo Research Grant,Toyo University respectively for the financial support provided to carry out this work。
文摘The evolving dynamics of drug resistance due to tumor heterogeneity often creates impediments to traditional therapies making it a challenging issue for cancer cure.Breast cancer often faces challenges of current therapeutic interventions owing to its multiple complexities and high drug resistivity,for example against drugs like trastuzumab and tamoxifen.Drug resistance in the majority of breast cancer is often aided by the overtly expressed P-glycoprotein(P-gp)that guides in the rapid drug efflux of chemotherapy drugs.Despite continuous endeavors and ground-breaking achievements in the pursuit of finding better cancer therapeutic avenues,drug resistance is still a menace to hold back.Among newer therapeutic approaches,the application of phytonutrients such as alkaloids to suppress P-gp activity in drug-resistant cancers has found an exciting niche in the arena of alternative cancer therapies.In this work,we would like to present a black pepper alkaloid derivative known as Bio Perine-loaded chitosan(CS)-polyethylene glycol(PEG)coated polylactic acid(PLA)hybrid polymeric nanoparticle to improve the bioavailability of Bio Perine and its therapeutic efficacy in suppressing P-gp expression in MDA-MB 453 breast cancer cell line.Our findings revealed that the CS-PEG-Bio PerinePLA nanoparticles demonstrated a smooth spherical morphology with an average size of316 nm,with improved aqueous solubility,and provided sustained Bio Perine release.The nanoparticles also enhanced in vitro cytotoxicity and downregulation of P-gp expression in MDA-MB 453 cells compared to the commercial inhibitor verapamil hydrochloride,thus promising a piece of exciting evidence for the development of Bio Perine based nano-drug delivery system in combination with traditional therapies as a crucial approach to tackling multi-drug resistance in cancers.
