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Open AccessArticle

Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid)

1
Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA
2
Institut für Biophysik und Physikalische Biochemie der Universität Regensburg, Regensburg 93053, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2012, 13(9), 11681-11693; https://doi.org/10.3390/ijms130911681
Received: 12 July 2012 / Revised: 17 August 2012 / Accepted: 7 September 2012 / Published: 17 September 2012
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
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. View Full-Text
Keywords: polymalic acid; doxorubicin; nanoconjugate; pH-controlled hydrazine linkage; brain and breast cancer polymalic acid; doxorubicin; nanoconjugate; pH-controlled hydrazine linkage; brain and breast cancer
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MDPI and ACS Style

Patil, R.; Portilla-Arias, J.; Ding, H.; Konda, B.; Rekechenetskiy, A.; Inoue, S.; Black, K.L.; Holler, E.; Ljubimova, J.Y. Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid). Int. J. Mol. Sci. 2012, 13, 11681-11693.

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