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Nanoconjugates of poly(malic acid) with functional modules for drug delivery

J.Y. Ljubimova, M. Fujita, B.-S. Lee, N.M. Khazenzon, S. Wachsmann-Hogiu, D.L. Farkas, K.L. Black and E. Holler
Cedars-Sinai Medical Center, US

Keywords:
antisense oligonucleotides, antibodies, tissue targeting, fluorescence imaging, tumor angiogenesis

Abstract:
Nanoconjugates of β-poly(L-malic acid) (PMLA) have been synthesized with modules active in drug delivery, drug release, blocking of tumor-affiliated mRNA by antisense oligonucleotides, penetration of blood and cellular barriers, tissue targeting, membrane permeation, fluorescence, and protection. PMLA of microbial origin is non-toxic, nonimmunogenic, biodegradable and highly suited as a scaffold for tailored nanoconjugate chemistry. The nanoconjugate of 550 kDa allowed fluorescence imaging of brain tumor and breast cancer implanted on mouse, targeted on the basis of tumor tissue-inherent enhanced permeability and retention (EPR) and antibody recognition. The nanoconjugates were designed to inhibit tumor growth by preventing angiogenesis.

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