Redox potential ultrasensitive nanoparticle for the targeted delivery of camptothecin to HER2-positive cancer cells.
Ideal "smart" nanoparticles for drug delivery should enhance therapeutic efficacy without introducing side effects. To achieve that, we developed a drug delivery system (HCN) based on a polymer-drug conjugate of poly[2-(pyridin-2-yldisulfanyl)]-graft-poly(ethylene glycol) and camptothecin with an intracellularly cleavable linker and human epidermal growth factor receptor 2 (HER2) targeting ligands. An in vitro drug release study found that HCN was stable in the physiological environment and supersensitive to the stimulus of elevated intracellular redox potential, releasing all payloads in less than 30 min. Furthermore, confocal microscopy revealed that HCN could specifically enter HER2-positive cancer cells. As a consequence, HCN could effectively kill HER2-positive cancer cells while not affecting HER2-negative cells.
Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina , 715 Sumter Street, Columbia, South Carolina 29208, United States.
Bahadur K C
BK
Remant
Varun
V
Chandrashekaran
Bei
B
Cheng
Hexin
H
Chen
Maria Marjorette O
MM
Peña
Jiajia
J
Zhang
Janis
J
Montgomery
Peisheng
P
Xu
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007624:KB Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
D002166:Camptothecin; D004317:Doxorubicin; D011092:Polyethylene Glycols; D011108:Polymers; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human