Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells

被引：1213

作者：

Kim, Myung Soo ^{[1
,2
]}

Haney, Matthew J. ^{[1
,2
]}

Zhao, Yuling ^{[1
,2
]}

Mahajan, Vivek ^{[1
,2
]}

Deygen, Irina ^{[3
]}

Klyachko, Natalia L. ^{[1
,2
,3
]}

Inskoe, Eli ^{[2
]}

Piroyan, Aleksandr ^{[1
,2
]}

Sokolsky, Marina ^{[1
,2
]}

Okolie, Onyi ^{[2
]}

Hingtgen, Shawn D. ^{[1
,2
]}

Kabanov, Alexander V. ^{[1
,2
,3
]}

Batrakova, Elena V. ^{[1
,2
]}

机构：

[1] Univ N Carolina, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC USA

[2] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA

[3] Moscow MV Lomonosov State Univ, Fac Chem, Dept Chem Enzymol, Moscow 117234, Russia

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2016年 / 12卷 / 03期

基金：

俄罗斯科学基金会; 美国国家卫生研究院;

关键词：

Cancer; Drug resistance; Exosome; Paclitaxel; Pgp; PLURONIC BLOCK-COPOLYMERS; DRUG-DELIVERY VEHICLES; BRAIN; NANOPARTICLES; SENSITIZATION; NANOMEDICINE; DOXORUBICIN; MEDIATORS; CURCUMIN; VECTOR;

D O I：

10.1016/j.nano.2015.10.012

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Exosomes have recently come into focus as "natural nanoparticles" for use as drug delivery vehicles. Our objective was to assess the feasibility of an exosome-based drug delivery platform for a potent chemotherapeutic agent, paclitaxel (PTX), to treat MDR cancer. Herein, we developed different methods of loading exosomes released by macrophages with PTX (exoPTX), and characterized their size, stability, drug release, and in vitro antitumor efficacy. Reformation of the exosomal membrane upon sonication resulted in high loading efficiency and sustained drug release. Importantly, incorporation of PTX into exosomes increased cytotoxicity more than 50 times in drug resistant MDCKMDR1 (Pgp+) cells. Next, our studies demonstrated a nearly complete co-localization of airway-delivered exosomes with cancer cells in a model of murine Lewis lung carcinoma pulmonary metastases, and a potent anticancer effect in this mouse model. We conclude that exoPTX holds significant potential for the delivery of various chemotherapeutics to treat drug resistant cancers. Published by Elsevier Inc.

引用

页码：655 / 664

页数：10

共 47 条

[1] The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage [J].

Abu Lila, Amr S. ;

Kiwada, Hiroshi ;

Ishida, Tatsuhiro .

JOURNAL OF CONTROLLED RELEASE, 2013, 172 (01) :38-47

[2] Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes [J].

Alvarez-Erviti, Lydia ;

Seow, Yiqi ;

Yin, HaiFang ;

Betts, Corinne ;

Lakhal, Samira ;

Wood, Matthew J. A. .

NATURE BIOTECHNOLOGY, 2011, 29 (04) :341-U179

[3] Fundamental relationships between the composition of Pluronic block copolymers and their hypersensitization effect in MDR cancer cells [J].

Batrakova, E ;

Lee, S ;

Li, S ;

Venne, A ;

Alakhov, V ;

Kabanov, A .

PHARMACEUTICAL RESEARCH, 1999, 16 (09) :1373-1379

[4] Alteration of genomic responses to doxorubicin and prevention of MDR in breast cancer cells by a polymer excipient: Pluronic P85 [J].

Batrakova, Elena V. ;

Kelly, David L. ;

Li, Shu ;

Li, Yili ;

Yang, Zhihui ;

Xiao, Li ;

Alakhova, Daria Y. ;

Sherman, Simon ;

Alakhov, Valery Yu. ;

Kabanov, Alexander V. .

MOLECULAR PHARMACEUTICS, 2006, 3 (02) :113-123

[5] Effects of pluronic and doxorubicin on drug uptake, cellular metabolism, apoptosis and tumor inhibition in animal models of MDR cancers [J].

Batrakova, Elena V. ;

Li, Shu ;

Brynskikh, Anna M. ;

Sharma, Amit K. ;

Li, Yili ;

Boska, Michael ;

Gong, Nan ;

Mosley, R. Lee ;

Alakhov, Valery Yu. ;

Gendelman, Howard E. ;

Kabanov, Alexander V. .

JOURNAL OF CONTROLLED RELEASE, 2010, 143 (03) :290-301

[6] Optimal structure requirements for pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells [J].

Batrakova, EV ;

Li, S ;

Alakhov, VY ;

Miller, DW ;

Kabanov, AV .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 304 (02) :845-854

[7] Sensitization of cells overexpressing multidrug-resistant proteins by Pluronic P85 [J].

Batrakova, EV ;

Li, S ;

Alakhov, VY ;

Elmquist, WF ;

Miller, DW ;

Kabanov, AV .

PHARMACEUTICAL RESEARCH, 2003, 20 (10) :1581-1590

[8] Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion [J].

Batrakova, EV ;

Li, S ;

Elmquist, WF ;

Miller, DW ;

Alakhov, VY ;

Kabanov, AV .

BRITISH JOURNAL OF CANCER, 2001, 85 (12) :1987-1997

[9] A phase I and pharmacologic study of idarubicin, cytarabine, etoposide, and the multidrug resistance protein (MDR1/Pgp) inhibitor PSC-833 in patients with refractory leukemia [J].

Bauer, KS ;

Karp, JE ;

Garimella, TS ;

Wu, SL ;

Tan, M ;

Ross, DD .

LEUKEMIA RESEARCH, 2005, 29 (03) :263-271

[10]

Boldytev I A, 2006, Bioorg Khim, V32, P87

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