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

被引：70

作者：

Patil, Rameshwar ^{[1
]}

Portilla-Arias, Jose ^{[1
]}

Ding, Hui ^{[1
]}

Konda, Bindu ^{[1
]}

Rekechenetskiy, Arthur ^{[1
]}

Inoue, Satoshi ^{[1
]}

Black, Keith L. ^{[1
]}

Holler, Eggehard ^{[1
,2
]}

Ljubimova, Julia Y. ^{[1
]}

机构：

[1] Cedars Sinai Med Ctr, Dept Neurosurg, Nanomed Res Ctr, Los Angeles, CA 90048 USA

[2] Univ Regensburg, Inst Biophys & Phys Biochem, D-93053 Regensburg, Germany

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2012年 / 13卷 / 09期

关键词：

polymalic acid; doxorubicin; nanoconjugate; pH-controlled hydrazine linkage; brain and breast cancer; MULTIDRUG-RESISTANCE; TUMOR; EFFICACY; COPOLYMERS; MECHANISMS; GROWTH;

D O I：

10.3390/ijms130911681

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(beta-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.

引用

页码：11681 / 11693

页数：13

共 42 条

[1]

[Anonymous], 1996, 13321 ISO

[2]

[Anonymous], 1997, HDB ENG POL MAT

[3] Doxil® - The first FDA-approved nano-drug: Lessons learned [J].

Barenholz, Yechezkel .

JOURNAL OF CONTROLLED RELEASE, 2012, 160 (02) :117-134

[4]

Bolhuis H, 1997, FEMS MICROBIOL REV, V21, P55, DOI 10.1111/j.1574-6976.1997.tb00345.x

[5] A family of drug transporters: The multidrug resistance-associated proteins [J].

Borst, P ;

Evers, R ;

Kool, M ;

Wijnholds, J .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (16) :1295-1302

[6] Synthesis of polyglutamine and dextran conjugates of streptomycin with an acid-sensitive drug-carrier linkage [J].

Coessens, V ;

Schacht, E ;

Domurado, D .

JOURNAL OF CONTROLLED RELEASE, 1996, 38 (2-3) :141-150

[7] Inhibition of brain tumor growth by intravenous poly (β-L-malic acid) nanobioconjugate with pH-dependent drug release [J].

Ding, Hui ;

Inoue, Satoshi ;

Ljubimov, Alexander V. ;

Patil, Rameshwar ;

Portilla-Arias, Jose ;

Hu, Jinwei ;

Konda, Bindu ;

Wawrowsky, Kolja A. ;

Fujita, Manabu ;

Karabalin, Natalya ;

Sasakie, Takako ;

Black, Keith L. ;

Holler, Eggehard ;

Ljubimova, Julia Y. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (42) :18143-18148

[8] Polymer-drug conjugates: towards a novel approach for the treatment of endrocine-related cancer [J].

Duncan, R ;

Vicent, MJ ;

Greco, F ;

Nicholson, RI .

ENDOCRINE-RELATED CANCER, 2005, 12 :S189-S199

[9] The dawning era of polymer therapeutics [J].

Duncan, R .

NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (05) :347-360

[10] Cancer nanotechnology: Opportunities and challenges [J].

Ferrari, M .

NATURE REVIEWS CANCER, 2005, 5 (03) :161-171

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