Journal
BIOMATERIALS
Volume 35, Issue 20, Pages 5414-5424Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.03.046
Keywords
Liposomes; Polymers; Tumor; ECM-induced targeting; Intracellular drug delivery; Cancer therapy
Funding
- National Science Council of the Republic of China (Taiwan) (NSC) [100-2320-B-010-007-MY3, 101-2221-E-010-002-MY2, 102-2627-E-010-001]
- Yen Tjing Ling Medical Foundation [CI-103-9]
- National Research Program for Biopharmaceuticals (NRPB) at the NSC of Taiwan
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This study presents a tumor-extracellular matrix pH-induced targeting liposome (ECM-targeting liposomes), crosslinked from methoxy-poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide-co-histidine)-cholesterol copolymers and biotin2-polyethylene glycol crosslinkers by hydrogen bonds to overcome the defects of liposomes. In this study, ECM-targeting liposomes were completely investigated their pH-responsibility, drug releasing behaviors, anticancer efficiencies and the time-dependent organ distribution and toxic effects. Experimental results indicate that ECM-targeting liposomes showed rapid drug releasing profiles in acidic conditions. Because the ECM-targeting liposomes accumulated preferentially in tumor, the ECM-targeting liposomes exhibited exceptional anticancer activity in vivo and lower hepatic and renal toxicity. The ECM-targeting liposomes which are switched on the targeting ability in tumor ECM possess potential for future application in anticancer therapy. (C) 2014 Elsevier Ltd. All rights reserved.
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