Open AccessRedox Potential Ultrasensitive Nanoparticle for the Targeted Delivery of Camptothecin to HER2-Positive Cancer Cells
Author(s) -
Remant Bahadur K.C.,
Varun Chandrashekaran,
Bei Cheng,
Hexin Chen,
Maria Marjorette O. Peña,
Jiajia Zhang,
Janis Montgomery,
Peisheng Xu
Publication year - 2014
Publication title -
molecular pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 127
eISSN - 1543-8392
pISSN - 1543-8384
DOI - 10.1021/mp5000482
Subject(s) - camptothecin , chemistry , ethylene glycol , conjugate , drug delivery , cancer cell , confocal microscopy , biophysics , in vitro , linker , redox , drug , intracellular , pharmacology , biochemistry , cancer , microbiology and biotechnology , biology , organic chemistry , mathematical analysis , mathematics , computer science , genetics , operating system
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.
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