title: Doxorubicin-loaded alginate-g-poly(N-isopropylacrylamide) micelles for cancer imaging and therapy.
abstract: Chemotherapy is a widely adopted method for the treatment of cancer. However, its use is often limited due to side effects produced by anti-cancer drugs. Therefore, various drug carriers, including polymeric micelles, have been investigated to find a method to overcome this limitation. In this study, alginate-based, self-assembled polymeric micelles were designed and prepared using alginate-g-poly(N-isopropylacrylamide) (PNIPAAm). Amino-PNIPAAm was chemically introduced to the alginate backbone via carbodiimide chemistry. The resulting polymer was dissolved in distilled water at room temperature and formed self-assembled micelles at 37 °C. Characteristics of alginate-g-PNIPAAm micelles were dependent on the molecular weight of PNIPAAm, the degree of substitution, and the polymer concentration. Doxorubicin (DOX), a model anti-cancer drug, was efficiently encapsulated in alginate-g-PNIPAAm micelles, and sustained release of DOX from the micelles was achieved at 37 °C in vitro. These micelles accumulated at the tumor site of a tumor-bearing mouse model as a result of the enhanced permeability and retention effect. Interestingly, DOX-loaded alginate-g-PNIPAAm micelles showed excellent anti-cancer therapeutic efficacy in a mouse model without any significant side effects. This approach to designing and tailoring natural polymer-based systems to fabricate nanoparticles at human body temperature may provide a useful means for cancer imaging and therapy.
authors.affiliation: Department of Bioengineering, Hanyang University , Seoul 133-791, Republic of Korea.
authors.forename: Dong-Gyun
authors.initials: DG
authors.lastname: Ahn
authors.forename: Jangwook
authors.initials: J
authors.lastname: Lee
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Young-Je
authors.initials: YJ
authors.lastname: Kwark
authors.forename: Kuen Yong
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D051379:Mice; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D016896:Treatment Outcome
chemical_list: D000180:Acrylic Resins; D000464:Alginates; D000970:Antineoplastic Agents; D006603:Hexuronic Acids; D008823:Micelles; D053769:Nanocapsules; C052970:poly-N-isopropylacrylamide; D004317:Doxorubicin; D020723:Glucuronic Acid
keywords: alginate; cancer; diagnosis; micelle; therapy