Cellular Delivery of Doxorubicin Via PH-controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-l-malic Acid)

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2012 Oct 31

PMID 23109877

Citations 30

Authors

Rameshwar Patil

Jose Portilla-Arias

Hui Ding

Bindu Konda

Arthur Rekechenetskiy

Satoshi Inoue

Keith L Black

Eggehard Holler

Julia Y Ljubimova

Affiliations

Soon will be listed here.

Abstract

Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β-l-malic acid) (PMLA). DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.

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