A dermatan sulfate-functionalized biomimetic nanocarrier for melanoma targeted chemotherapy

Carbohydr Polym. 2020 May 1:235:115983. doi: 10.1016/j.carbpol.2020.115983. Epub 2020 Feb 15.

Abstract

Melanoma is a malignant tumor of melanocytes that is a serious threat to human health. Dermatan sulfate (DS) is a natural glycosaminoglycan. Inspired by the origin of DS, we report a DS-functionalized biomimetic chitosan nanocarrier (DCNP) for melanoma targeted chemotherapy. DS can anchor to the surface of the chitosan nanocarrier (CNP) by forming amide bond. The SN38/DCNP can rapidly release the anti-tumor drug under acidic conditions. The functionalization of DS not only promoted the specific uptake behavior of melanoma cells, but also up-regulated cleaved caspase-3 and PARP promote tumor cell apoptosis. In vivo model, DCNP reduced the non-specific distribution of SN38 in the circulation and other tissues, while shows superior tumor targeting ability. SN38/DCNP significantly inhibit tumor growth and improved the survival rate. Moreover, SN38/DCNP has a milder myelosuppressive effect. The above results indicated that DS could be used as an excellent targeting unit for the treatment of melanoma.

Keywords: Biomimetic; Dermatan sulfate; Melanoma; Targeted therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Biomimetic Materials / administration & dosage
  • Biomimetic Materials / chemistry*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology*
  • Cell Proliferation / drug effects
  • Dermatan Sulfate / administration & dosage
  • Dermatan Sulfate / chemistry*
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Liberation
  • Drug Screening Assays, Antitumor
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mice
  • Molecular Structure
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Particle Size
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Surface Properties
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Dermatan Sulfate
  • Camptothecin