Doxorubicin-loaded alginate-g-poly(N-isopropylacrylamide) micelles for cancer imaging and therapy

ACS Appl Mater Interfaces. 2014 Dec 24;6(24):22069-77. doi: 10.1021/am505444c. Epub 2014 Dec 9.

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.

Keywords: alginate; cancer; diagnosis; micelle; therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry*
  • Alginates / chemistry*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Diffusion
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Mice
  • Micelles
  • Nanocapsules* / administration & dosage
  • Nanocapsules* / chemistry
  • Particle Size
  • Treatment Outcome

Substances

  • Acrylic Resins
  • Alginates
  • Antineoplastic Agents
  • Hexuronic Acids
  • Micelles
  • Nanocapsules
  • poly-N-isopropylacrylamide
  • Doxorubicin
  • Glucuronic Acid