Quercetin-Based Modified Porous Silicon Nanoparticles for Enhanced Inhibition of Doxorubicin-Resistant Cancer Cells

Adv Healthc Mater. 2017 Feb;6(3). doi: 10.1002/adhm.201601009. Epub 2016 Dec 12.

Abstract

One of the most challenging obstacles in nanoparticle's surface modification is to achieve the concept that one ligand can accomplish multiple purposes. Upon such consideration, 3-aminopropoxy-linked quercetin (AmQu), a derivative of a natural flavonoid inspired by the structure of dopamine, is designed and subsequently used to modify the surface of thermally hydrocarbonized porous silicon (PSi) nanoparticles. This nanosystem inherits several advanced properties in a single carrier, including promoted anticancer efficiency, multiple drug resistance (MDR) reversing, stimuli-responsive drug release, drug release monitoring, and enhanced particle-cell interactions. The anticancer drug doxorubicin (DOX) is efficiently loaded into this nanosystem and released in a pH-dependent manner. AmQu also effectively quenches the fluorescence of the loaded DOX, thereby allowing the use of the nanosystem for monitoring the intracellular drug release. Furthermore, a synergistic effect with the presence of AmQu is observed in both normal MCF-7 and DOX-resistant MCF-7 breast cancer cells. Due to the similar structure as dopamine, AmQu may facilitate both the interaction and internalization of PSi into the cells. Overall, this PSi-based platform exhibits remarkable superiority in both multifunctionality and anticancer efficiency, making this nanovector a promising system for anti-MDR cancer treatment.

Keywords: cellular interactions; dopamine-inspired flavonoid; multiple drug resistance; pH-sensitive; porous silicon nanoparticles.

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • MCF-7 Cells
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Porosity
  • Quercetin* / chemistry
  • Quercetin* / pharmacology
  • Silicon* / chemistry
  • Silicon* / pharmacology

Substances

  • Drug Carriers
  • Doxorubicin
  • Quercetin
  • Silicon