pH-responsive polymer-liposomes for intracellular drug delivery and tumor extracellular matrix switched-on targeted cancer therapy.
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.
Department of Biomedical Engineering, National Yang Ming University, Taipei 112, Taiwan, ROC.
Yi-Ting
YT
Chiang
Department of Biomedical Engineering, National Yang Ming University, Taipei 112, Taiwan, ROC; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang Ming University, Taipei 112, Taiwan, ROC; Biomedical Engineering Research Center, National Yang Ming University, Taipei 112, Taiwan, ROC. Electronic address: cllo@ym.edu.tw.
Chun-Liang
CL
Lo
D000178:Acrylamides / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000178:Acrylamides; D000970:Antineoplastic Agents; D008081:Liposomes; D011108:Polymers; C000593609:methoxy-poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide-co-histidine)cholesterol; D011092:Polyethylene Glycols; D001710:Biotin; D004317:Doxorubicin
Cancer therapy; Intracellular drug delivery; Liposomes; Polymers; Tumor ECM-induced targeting