Photothermal cancer immunotherapy by erythrocyte membrane-coated black phosphorus formulation

J Control Release. 2019 Feb 28:296:150-161. doi: 10.1016/j.jconrel.2019.01.027. Epub 2019 Jan 23.

Abstract

Basal-like breast cancer exhibits a triple-negative phenotype and has a poor prognosis, even with traditional chemical and anti-human epidermal growth factor receptor (HER) treatments. However, the high mutation rate of this obstinate cancer type renders it suitable for immunotherapy. Photothermal therapy (PTT) is a high-efficiency method for inducing tumor neoantigen release in situ, which has great potential for use in cancer immunotherapy. Here, we prepared a biomimetic black phosphorus quantum dot (BPQDs) formulation to induce breast cancer cell apoptosis in situ by near-infrared (NIR) laser irradiation to mobilize the immune system to eliminate the residual and metastatic cancer cells. Erythrocyte membranes (RMs) were used to coat the BPQDs, forming a BPQD-RM nanovesicle (BPQD-RMNV) biomimetic formulation that exhibited a long circulation time and tumor accumulation in vivo. The basal-like 4T1 breast tumor underwent apoptosis and necrosis with the irradiation and recruited dendritic cells (DCs) to capture the tumor antigens in vivo. Furthermore, programmed cell death protein 1 (PD-1) antibody (aPD-1) was employed to prevent the CD8+ T cells from exhaustion. Notably, BPQD-RMNV-mediated PTT combined with aPD-1 treatment significantly delayed residual and metastatic tumor growth in vivo. Hence, BPQD-RMNV-mediated PTT combined with immune checkpoint blockade antibody increased the infiltration and activity of CD8+ T cells in the tumor, which directly restrained basal-like breast tumor growth in vivo.

Keywords: Black phosphorus quantum dot; Erythrocyte membrane; Immune checkpoint blockade; PD-1 antibody; Photothermal therapy; Triple-negative phenotype basal-like breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / microbiology
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Erythrocyte Membrane*
  • Female
  • Humans
  • Immunotherapy*
  • Lasers*
  • Mice, Inbred BALB C
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Phosphorus / administration & dosage*
  • Phosphorus / pharmacokinetics
  • Phototherapy*
  • Quantum Dots / administration & dosage*

Substances

  • Phosphorus