Mn-porphyrin conjugated Au nanoshells encapsulating doxorubicin for potential magnetic resonance imaging and light triggered synergistic therapy of cancer

Theranostics. 2014 Jun 11;4(9):858-71. doi: 10.7150/thno.8818. eCollection 2014.

Abstract

A theranostic agent was successfully fabricated by the formation of Au nanoshell around poly(lactic acid) nanoparticles entrapping doxorubicin, followed by linking a Mn-porphyrin derivative on the Au shell surface through polyethylene glycol. The resulted agent exhibited excellent colloidal stability and long blood circulation time due to introducing polyethylene glycol. The grafting Mn-porphyrin onto the nanoparticle surface endowed a greatly improved relaxivity (r1 value of 22.18 mM(-1)s(-1) of Mn(3+)), favorable for accurate cancer diagnosing and locating the tumor site to guide the external near infrared (NIR) laser irradiation for photothermal ablation of tumors. The in vitro experiments confirmed that the agent exhibited an efficient photohyperthermia and a light triggered and stepwise release behavior of doxorubicin due to the high NIR light absorption coefficient of Au nanoshell. The in vivo experiments showed that the combination of chemotherapy and photothermal therapy through such theranostic agent offered a synergistically improved therapeutic outcome compared with either therapy alone, making it a promising approach for cancer therapy. Therefore, such theranostic agent can be developed as a smart and promising nanosystemplatform that integrates multiple capabilities for both effective contrast enhanced magnetic resonance imaging and synergistic therapy.

Keywords: Au nanoshell; chemotherapy; magnetic resonance imaging.; photothermal therapy; porphyrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / therapeutic use*
  • Cell Line, Tumor
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use*
  • Gold / chemistry
  • Humans
  • Lactic Acid / chemistry
  • Low-Level Light Therapy*
  • Magnetic Resonance Imaging
  • Male
  • Manganese / chemistry*
  • Mice
  • Mice, Nude
  • Nanoshells*
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Polyesters
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Porphyrins / chemistry*
  • Rats
  • Rats, Wistar

Substances

  • Antibiotics, Antineoplastic
  • Polyesters
  • Polymers
  • Porphyrins
  • Lactic Acid
  • Polyethylene Glycols
  • Manganese
  • poly(lactide)
  • Gold
  • Doxorubicin