New organic/inorganic nanohybrids of targeted pullulan derivative/gold nanoparticles for effective drug delivery systems

Int J Biol Macromol. 2020 Nov 1:162:561-577. doi: 10.1016/j.ijbiomac.2020.06.089. Epub 2020 Jun 15.

Abstract

This study aimed to develop new organic/inorganic nanohybrids of targeted pullulan derivative/gold nanoparticles (FA-PABA-Q188-PUL@AuNPs) to improve the selectivity and efficacy of drugs. The chemical structure of targeted pullulan derivative, folic acid-decorated para-aminobenzoic acid-quat188-pullulan (FA-PABA-Q188-PUL), was designed for reducing, stabilizing, capping, and functionalizing AuNPs. Here, the key factors, including pH, temperature, and FA-PABA-Q188-PUL concentrations, were systematically optimized to control the morphology, size, and functionalization of multifunctional FA-PABA-Q188-PUL@AuNPs. Spherical FA-PABA-Q188-PUL@AuNPs obtained by a green, simple, and bio-inspired strategy under the optimum conditions were thoroughly characterized and had an average size of 12.6 ± 1.5 nm. The anticancer drug DOX was successfully loaded on monodispersed FA-PABA-Q188-PUL@AuNPs and the system exhibited excellent intracellular uptake, specificity, and physicochemical properties. The pH-responsive DOX release from FA-PABA-Q188-PUL@AuNPs-DOX showed fast release (85% after 72 h) under acidic conditions. Furthermore, FA-PABA-Q188-PUL@AuNPs-DOX enhanced the anticancer activity of DOX toward Chago-k1 cancer cells up to 4.8-fold and showed less cytotoxicity toward normal cells than free DOX. The FA-PABA-Q188-PUL@AuNPs-DOX induced the death of cells by increasing late apoptotic cells (26.4%) and arresting the cell cycle at S-G2/M phases. These results showed that innovative FA-PABA-Q188-PUL@AuNPs should be considered as new candidate platforms for anticancer drug delivery systems.

Keywords: Drug delivery systems; Organic/inorganic nanohybrids; Pullulan derivative/gold nanoparticles.

MeSH terms

  • A549 Cells
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Carriers* / pharmacology
  • Glucans* / chemistry
  • Glucans* / pharmacokinetics
  • Glucans* / pharmacology
  • Gold* / chemistry
  • Gold* / pharmacokinetics
  • Gold* / pharmacology
  • Hep G2 Cells
  • Humans
  • Metal Nanoparticles* / chemistry
  • Metal Nanoparticles* / therapeutic use
  • Nanocomposites* / chemistry
  • Nanocomposites* / therapeutic use
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology

Substances

  • Drug Carriers
  • Glucans
  • Gold
  • Doxorubicin
  • pullulan