Paclitaxel/sunitinib-loaded micelles promote an antitumor response in vitro through synergistic immunogenic cell death for triple-negative breast cancer

Nanotechnology. 2020 Sep 4;31(36):365101. doi: 10.1088/1361-6528/ab94dc. Epub 2020 May 20.

Abstract

Chemotherapy-induced immunogenic cell death (ICD) may offer a strategy to improve the effect of the therapeutic treatment of triple-negative breast cancer (TNBC) by eliciting broad antitumor immunity. However, chemotherapy shows a limited therapeutic effect because of multi-drug resistance and the immunosuppressive tumor microenvironment (TME) of TNBC. The unique pharmacological actions of sunitinib (SUN) indicate its possible synergies with paclitaxel (PTX) to enhance chemo-immunotherapy for TNBC. Here, we prepared a co-delivery platform composed of poly(styrene-co-maleic anhydride) (SMA) via a self-assembly process for a combination of PTX and SUN, which was able to induce a higher synergistic ICD. The nanomicellar delivery of PTX and SUN loaded at an optimal ratio of 1:5 (PTX:SUN) presented the characteristics of an appropriate particle size, long-term stability, and time sequence release which synergistically promoted the apoptosis of MDA-MB-231 tumor cells. Moreover, we demonstrated that the combination of PTX and SUN could significantly induce a synergistic effect because it promoted an ICD response, improved tumor immunogenicity, and regulated immunosuppressive factors in the TME. Overall, PTX and SUN with synergistic effects entrapped in a self-assembly nano-delivery system could offer the potential for clinical applicationof a combination chemo-immunotherapy strategy to improve the effect of the therapeutic treatment of TNBC.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Stability
  • Drug Synergism
  • Female
  • Humans
  • Immunogenic Cell Death
  • Maleates / chemistry
  • Mice
  • Micelles
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Particle Size
  • Polystyrenes / chemistry
  • Sunitinib / administration & dosage*
  • Sunitinib / chemistry
  • Sunitinib / pharmacology
  • Triple Negative Breast Neoplasms / drug therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Maleates
  • Micelles
  • Polystyrenes
  • poly(styrene-co-maleic anhydride)
  • Paclitaxel
  • Sunitinib