Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy

Int J Nanomedicine. 2012;7:4037-51. doi: 10.2147/IJN.S32804. Epub 2012 Jul 30.

Abstract

Background: We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer.

Methods: Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid), docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs), a multilayer shell formed by poly(allylamine hydrochloride) and two different sized poly(ethylene glycol) molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery.

Results: Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001).

Conclusion: This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo.

Keywords: chemotherapy; imaging; nanoparticle; prostate cancer; targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics
  • Docetaxel
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics
  • GPI-Linked Proteins / chemistry
  • GPI-Linked Proteins / metabolism
  • HT29 Cells
  • Humans
  • Immunoconjugates / chemistry*
  • Immunoconjugates / immunology
  • Lactic Acid / chemistry
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / metabolism
  • Phantoms, Imaging
  • Polyamines / chemistry
  • Polyethylene Glycols / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Taxoids / chemistry
  • Taxoids / pharmacokinetics
  • Taxoids / pharmacology

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Contrast Media
  • Drug Carriers
  • GPI-Linked Proteins
  • Immunoconjugates
  • Magnetite Nanoparticles
  • Neoplasm Proteins
  • PSCA protein, human
  • Polyamines
  • Taxoids
  • Docetaxel
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • polyallylamine
  • Lactic Acid
  • Polyethylene Glycols