%0 Journal Article %T Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(¦Â-L-Malic Acid) %A Rameshwar Patil %A Jose Portilla-Arias %A Hui Ding %A Bindu Konda %A Arthur Rekechenetskiy %A Satoshi Inoue %A Keith L. Black %A Eggehard Holler %A Julia Y. Ljubimova %J International Journal of Molecular Sciences %D 2012 %I MDPI AG %R 10.3390/ijms130911681 %X 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(¦Â-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. %K polymalic acid %K doxorubicin %K nanoconjugate %K pH-controlled hydrazine linkage %K brain and breast cancer %U http://www.mdpi.com/1422-0067/13/9/11681