Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery

J Nanobiotechnology. 2021 Nov 20;19(1):378. doi: 10.1186/s12951-021-01110-0.

Abstract

Background: Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m).

Results: Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n.

Conclusion: DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy.

Keywords: Biomimetic nanosuspensions; Blood–brain barrier; Chemotherapy; Glioma; Immunotherapy.

MeSH terms

  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Biomimetic Materials / chemistry
  • Blood-Brain Barrier / metabolism
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Female
  • Glioma / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nanoparticle Drug Delivery System*
  • Nanoparticles* / chemistry
  • Nanoparticles* / metabolism
  • RAW 264.7 Cells

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Nanoparticle Drug Delivery System