pH-Sensitive Black Phosphorous-Incorporated Hydrogel as Novel Implant for Cancer Treatment

J Pharm Sci. 2019 Aug;108(8):2542-2551. doi: 10.1016/j.xphs.2019.03.003. Epub 2019 Mar 13.

Abstract

In this study, black phosphorus nanosheets (BPNSs) were incorporated into a hydrogel formed from dibenzaldehyde-functionalized polymer (DF-PEG) and polyaspartylhydrazide (PAHy) polymer to create an injectable and pH-sensitive DF-PEG-PAHy/BPNSs hydrogel, which can be used as a smart depot for synergistic chemo-photothermal cancer therapy. The DF-PEG-PAHy/BPNSs hydrogel exhibited excellent gelation characteristics, pH sensitivity, and near-infrared responsiveness. The nanocomposite hydrogel provided controlled drug release and near-infrared irradiation speeded up release of drug from the hydrogel because of the photothermal effect of the BPNSs. Cytotoxicity tests confirmed that the hydrogel has good biocompatibility and exerts its photothermal effect in vitro. Antitumor tests in mice demonstrated the capacity of DF-PEG-PAHy/BPNSs hydrogel for synergistic chemo-photothermal therapy in vivo. The hydrogel showed reduced adverse effects because of stable drug release in the tumor area and an efficient photothermal effect. Together, these data demonstrated the potential of DF-PEG-PAHy/BPNSs hydrogel containing a chemotherapy drug to serve as a novel smart delivery system for combined chemo-photothermal cancer therapy.

Keywords: cancer; drug delivery system; hydrogel; nanocomposite; near-infrared spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use*
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / therapeutic use
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use*
  • Drug Delivery Systems
  • Female
  • Hydrogels / administration & dosage
  • Hydrogels / therapeutic use*
  • Hydrogen-Ion Concentration
  • Hyperthermia, Induced
  • Injections
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / therapy*
  • Phosphorus / administration & dosage
  • Phosphorus / therapeutic use*

Substances

  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Hydrogels
  • Phosphorus
  • Doxorubicin