Improved therapeutic effect of DOX-PLGA-PEG micelles decorated with bivalent fragment HAb18 F(ab')(2) for hepatocellular carcinoma.
Although surgery offers the only hope of cure for hepatocellular carcinoma (HCC), patients with inoperable or metastatic disease have a dismal prognosis. Therefore, there is an urgent need for new and effective treatment strategies. Polymeric micelles composed of drug conjugated to a diblock copolymer have attracted great interest for clinical administration of anticancer drugs. In this work, characteristics and cytotoxicity of doxorubicin-poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) (DOX-PLGA-PEG) micelle and its targeted micelle decorated with bivalent fragment HAb18 F(ab')(2) for HCC were studied. These micelles possessed spherical morphology and higher loading efficiency. Cellular uptake and accumulation in tumor tissue of micelles was observed. The accumulation of the targeted micelles depends on dual effects of passive and active targeting. The drug-loading micelles showed cytotoxicity on tumor cells in vitro and in vivo. The targeted micelles resulted in significant improvement in therapeutic response. These results suggest that the novel micelles could be a promising candidate with excellent therapeutic efficacy for targeting the drugs to cancer cells.
Jin
Cheng
C
Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Qian
Niansong
N
Zhao
Wei
W
Yang
Wenqing
W
Bai
Ling
L
Wu
Hong
H
Wang
Minchang
M
Song
Wenjie
W
Dou
Kefeng
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000627:therapeutic use*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D008823:Micelles; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin