Aptamer-functionalized albumin-based nanoparticles for targeted drug delivery

Colloids Surf B Biointerfaces. 2018 Nov 1:171:24-30. doi: 10.1016/j.colsurfb.2018.07.008. Epub 2018 Jul 5.

Abstract

Proteins have been extensively explored as versatile nanocarriers for drug delivery due to their complete biocompatibility, ease of surface modification, and lack of toxicity and immunogenicity. In this study, a facile strategy was used to construct aptamer-functionalized albumin-based nanoparticles for effective drug delivery and targeted cancer therapy. A hydrophobic drug, doxorubicin (DOX) was employed to trigger the self-assembly of bovine serum albumin (BSA) to from stable nanoparticles via hydrophobic interaction, and then a tumor targeting aptamer AS1411 was incorporated to the surface of DOX loaded BSA. Due to the specific recognition between AS1411 and its receptor over-expressed on tumor cells, the aptamer-modified nanoparticles show higher cellular uptake and stronger cell inhibitory efficacy against cancerous MCF-7 cells as compared with the nanoparticles without aptamer modification. In addition, DOX loaded aptamer-functionalized nanoparticles can induce more significant down-regulation of Bcl-2 and PCNA as well as up-regulation of pRB, PARP and Bax in MCF-7 cells compared with unmodified nanoparticles, indicating the aptamer modification can induce cell apoptosis more effectively. Besides, aptamer-modified nanoparticles exhibit a significantly improved capability in up-regulating p16, p21 and E-cadherin, and down-regulating EpCAM, vimentin, Snail, MMP-9, CD44 and CD133, implying the favorable effects of drug delivery on the prevention of tumor progression and metastasis.

Keywords: Aptamer; Cancer therapy; Drug delivery; Nanoparticles; Proteins.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Aptamers, Nucleotide / chemistry*
  • Cattle
  • Cell Proliferation / drug effects
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Drug Screening Assays, Antitumor
  • Humans
  • MCF-7 Cells
  • Nanoparticles / chemistry*
  • Particle Size
  • Serum Albumin, Bovine / chemistry*
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Drug Carriers
  • Serum Albumin, Bovine
  • Doxorubicin