title: In Vivo Biodistribution and Anti-Tumor Efficacy Evaluation of Doxorubicin and Paclitaxel-Loaded Pluronic Micelles Decorated with c(RGDyK) Peptide.
abstract: The treatment of squamous carcinoma, especially multidrug resistance (MDR) tumors, represents one of the most formidable challenges in oncology. In this study, integrin-mediated Pluronic-based micellar system (c(RGDyK)-FP-DP) was proposed as a drug delivery system to enhance the in vivo anti-tumor efficacy in MDR human squamous carcinoma (KBv)-bearing. Following the recognition by integrin proteins express on the cell surface, cellular uptake and in vitro anti-tumor efficacy of c(RGDyK)-FP-DP were better than conventional PF-DP in KBv cells. The tumor homing specificity and further in vivo anticancer efficacy of c(RGDyK)-FP-DP were performed using subcutaneous KBv tumor-bearing mice model, respectively. Compared with PF-DP, c(RGDyK)-FP-DP demonstrated more drug accumulation in tumor and relatively less drug accumulation in heart, and an extended median survival time in the KBv tumor-bearing mice model. Furthermore, preliminary in vivo subacute toxicity evaluation was also conducted by the measurement of histopathology, blood cell counts and clinical biochemistry parameters. Results showed that no obvious toxicity was observed to the hematological system or heart after a series of intravenous administration of c(RGDyK)-FP-DP. In conclusion, our results suggested that c(RGDyK) peptide conjugated Pluronic micelles could be a promising vehicle for enhancing the treatment of MDR human squamous carcinoma.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.|Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.|State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
authors.forename: Yanzuo
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.|CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, Virginia, 22209, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008823:Micelles; D009055:Mouth / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010456:Peptides, Cyclic; C550210:cyclo(Arg-Gly-Asp-Tyr-Lys); D020442:Poloxamer; D004317:Doxorubicin; D017239:Paclitaxel