title: Enhanced antitumor efficacy by d-glucosamine-functionalized and paclitaxel-loaded poly(ethylene glycol)-co-poly(trimethylene carbonate) polymer nanoparticles.
abstract: The poor selectivity of chemotherapeutics for cancer treatment may lead to dose-limiting side effects that compromise clinical outcomes. To solve the problem, surface-functionalized polymer nanoparticles are regarded as promising tumor-targeting delivery system. On the basis of glucose transporter (GLUT) overexpression on cancer cells, d-glucosamine-conjugated and paclitaxel-loaded poly(ethylene glycol)-co-poly(trimethylene carbonate) copolymer nanoparticles (DGlu-NP/PTX) were developed as potential tumor-targeting drug delivery system in this study. Because of the high affinity between d-glucosamine and GLUT, DGlu-NP/PTX could target to tumor tissue through GLUT-mediated endocytosis to improve the selectivity of PTX. DGlu-NP/PTX was prepared by emulsion/solvent evaporation technique and characterized in terms of morphology, size, and zeta potential. In vitro evaluation of two-dimensional cells and three-dimensional tumor spheroids revealed that DGlu-NP/PTX was more potent than those of plain nanoparticles (NP/PTX) and Taxol. In vivo multispectral fluorescent imaging indicated that DGlu-NP had higher specificity and efficiency on subcutaneous xenografts tumor of mouse. Furthermore, DGlu-NP/PTX showed the greatest tumor growth inhibitory effect on in vivo subcutaneous xenografts model with no evident toxicity. Therefore, these results demonstrated that DGlu-NP/PTX could be used as potential vehicle for cancer treatment.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China; Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Jiang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.forename: Jijin
authors.initials: J
authors.lastname: Gu
authors.forename: Fengyi
authors.initials: F
authors.lastname: Du
authors.forename: Chunlai
authors.initials: C
authors.lastname: Feng
authors.forename: Yike
authors.initials: Y
authors.lastname: Xie
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004146:Dioxanes / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry / Q000494:pharmacology; D004705:Endocytosis; D005944:Glucosamine / Q000737:chemistry* / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004146:Dioxanes; D004655:Emulsions; D051246:Glucose Transport Proteins, Facilitative; D011108:Polymers; D012997:Solvents; C059299:polytrimethylene carbonate; D011092:Polyethylene Glycols; D005944:Glucosamine; D017239:Paclitaxel
keywords: GLUT; biodegradable; biomaterials; cancer chemotherapy; d-Glucosamine; drug delivery system; nanoparticles; paclitaxel; polymers; tumor-targeting delivery system