Folate-decorated nanogels for targeted therapy of ovarian cancer

Biomaterials. 2011 Aug;32(23):5417-26. doi: 10.1016/j.biomaterials.2011.04.006. Epub 2011 May 4.

Abstract

Nanogels are comprised of swollen polymer networks and nearly 95% water and can entrap diverse chemical and biological agents for cancer therapy with very high loading capacities. Here we use diblock copolymer poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) to form nanogels with the desired degree of cross-linking. The nanogels are further conjugated to folic acid (FA) and loaded with different types of drugs (cisplatin, doxorubicin). For the first time we demonstrate a tumor-specific delivery and superior anti-tumor effect in vivo of an anti-cancer drug using these polyelectrolyte nanogels decorated with folate-targeting groups. This reinforces the use of nanogels for the therapy of ovarian and other cancers, where folate receptor (FR) is overexpressed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biological Availability
  • Body Weight / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / chemistry
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Delivery Systems / methods*
  • Endocytosis / physiology
  • Female
  • Folic Acid / chemistry*
  • Humans
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Light
  • Mice
  • Mice, Nude
  • Microscopy, Atomic Force
  • Nanoparticles / chemistry*
  • Osmolar Concentration
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Particle Size
  • Platinum / metabolism
  • Polyethylene Glycols / chemistry
  • Polymethacrylic Acids / chemistry
  • Scattering, Radiation
  • Static Electricity
  • Surface Properties
  • Survival Analysis
  • Water / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Hydrogels
  • Polymethacrylic Acids
  • poly(ethylene oxide)-b-poly(methacrylic acid)
  • Water
  • Polyethylene Glycols
  • Platinum
  • Doxorubicin
  • Folic Acid
  • Cisplatin