Methoxy poly(ethylene glycol)-poly(lactide) nanoparticles encapsulating quercetin act as an effective anticancer agent by inducing apoptosis in breast cancer

Pharm Res. 2015 Feb;32(2):723-35. doi: 10.1007/s11095-014-1504-2. Epub 2014 Sep 4.

Abstract

Purpose: To overcome the therapeutic restrictions offered by hydrophobic quercetin (Qu), this study aims to synthesize MPEG-PLA encapsulated Qu nanoparticle and to evaluate their anticancer efficacy.

Materials and methods: In vitro anticancer potential and apoptotic studies were done by cell cytotoxicity assay and flow cytometry, respectively. MPEG-PLA-Qu nanoparticles were evaluated for anticancer efficacy in vivo using xenograft mice model. TUNEL assay was performed to observe the frequency of apoptotic cells in vivo.

Results: The hydrodynamic particle size, polydispersity index, zeta potential and drug loading % of MPEG-PLA-Qu nanoparticle was 155.3 ± 3.2 nm, 0.2 ± 0.05, -3.14 mV and 5.3 ± 1.1%, respectively. Also, MPEG-PLA-Qu showed sustained drug release for 10 days. In vitro results showed that MPEG-PLA-Qu could efficiently induce apoptosis in triple negative breast cancer cell line (MDA-MB-231) with higher amount of quercetin in cell lysate treated with MPEG-PLA-Qu in comparison to free quercetin. In xenograft model for breast cancer, peritumorally injected MPEG-PLA-Qu significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in MPEG-PLA-Qu treated tumors compared to free quercetin at similar dose.

Conclusion: Our data suggest that MPEG-PLA-Qu nanoparticle can have a promising clinical potential for the treatment of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Polyesters / administration & dosage*
  • Polyesters / chemistry
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / chemistry
  • Quercetin / administration & dosage*
  • Quercetin / chemistry
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Polyesters
  • methoxy poly(ethylene glycol)-poly(lactide)
  • Polyethylene Glycols
  • Quercetin