Int. J. Mol. Sci. 2012, 13(9), 11681-11693; doi:10.3390/ijms130911681
Article

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.
Received: 12 July 2012; in revised form: 17 August 2012 / Accepted: 7 September 2012 / Published: 17 September 2012
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
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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.
Keywords: 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.

AMA Style

Patil R, Portilla-Arias J, Ding H, Konda B, Rekechenetskiy A, Inoue S, Black KL, Holler E, Ljubimova JY. Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid). International Journal of Molecular Sciences. 2012; 13(9):11681-11693.

Chicago/Turabian Style

Patil, Rameshwar; Portilla-Arias, Jose; Ding, Hui; Konda, Bindu; Rekechenetskiy, Arthur; Inoue, Satoshi; Black, Keith L.; Holler, Eggehard; Ljubimova, Julia Y. 2012. "Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid)." Int. J. Mol. Sci. 13, no. 9: 11681-11693.

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