Hydrazided hyaluronan/cisplatin/indocyanine green coordination nanoprodrug for photodynamic chemotherapy in liver cancer

Carbohydr Polym. 2022 Jan 15:276:118810. doi: 10.1016/j.carbpol.2021.118810. Epub 2021 Oct 26.

Abstract

It is still a huge challenge for concurrent highly efficient loading of chemotherapeutic agent and photosensitizer into single nanocarrier via stimuli-responsive linkages due to their different physicochemical properties and pharmacokinetics. Herein, based on the discovery of unique cisplatin-hydrazide and cisplatin-indocyanine green (ICG) coordination reactions, a multifunctional coordination nanoprodrug, cisplatin/ICG co-loaded hydrazided hyaluronan/bovine serum albumin (HBCI) nanoparticles, was developed by a desolvation-dual coordination process. The nanoprodrug exhibited ultrahigh drug loading efficiency and glutathione/NIR light dual-responsive drug release behavior. In vitro cellular studies demonstrated efficient internalization and apoptosis-inducing ability of the nanoprodrug in HepG2 cells. In vivo results confirmed the efficacious tumor accumulation and biosafety of HBCI nanoprodrug and synergistic effect of HBCI-based combined photodynamic chemotherapy on inhibiting tumor growth. Overall, this work not only provides a novel dual coordination approach for highly efficient loading of cisplatin and ICG but also verifies the therapeutic potential of HBCI nanoprodrug in combating hepatocellular carcinoma.

Keywords: Cisplatin; Coordination; Hyaluronan; Indocyanine green; Nanoprodrug.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Drug Delivery Systems / methods
  • Hep G2 Cells
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Indocyanine Green / chemistry
  • Indocyanine Green / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Prodrugs / chemistry
  • Prodrugs / pharmacology

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • Prodrugs
  • Hyaluronic Acid
  • Indocyanine Green
  • Cisplatin