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Engineering Cell-Derived Nanovesicles for Targeted Immunomodulation.

Adil Ali Sayyed1, Piyush Gondaliya1, Irene K Yan1

  • 1Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA.

Nanomaterials (Basel, Switzerland)
|October 27, 2023
PubMed
Summary
This summary is machine-generated.

Cell-derived nanovesicles (CDNVs) offer a promising alternative to extracellular vesicles (EVs) for drug delivery. These engineered nanovesicles demonstrate higher yields, enhanced loading capacity, and potent immunomodulatory capabilities for therapeutic applications.

Keywords:
RNA therapeuticsbiological nanoparticlescell-derived nanovesiclesimmunotherapytargeted delivery

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Area of Science:

  • Biotechnology and Nanomedicine
  • Cell Biology and Regenerative Medicine
  • Immunology and Cancer Therapy

Background:

  • Extracellular vesicles (EVs) are explored for targeted drug delivery but suffer from low production yields.
  • Cell-derived nanovesicles (CDNVs), created by reconstituting cell membranes, present a potential alternative to natural EVs.
  • Mesenchymal stem cells are a viable source for generating CDNVs with therapeutic potential.

Purpose of the Study:

  • To evaluate CDNVs derived from mesenchymal stem cells as substitutes for EVs in drug delivery.
  • To characterize the proteomic composition, toxicity, and loading capabilities of CDNVs.
  • To demonstrate the engineered immunomodulatory potential of CDNVs for cancer therapy.

Main Methods:

  • CDNVs were produced from mesenchymal stem cells using an extrusion method.
  • Proteomic analysis, in vitro cell-based assays (proliferation, DNA damage, nitric oxide production), and in vivo developmental toxicity studies were performed.
  • RNA and protein loading efficiencies were assessed, and surface protein engineering (PD1 expression) was conducted.

Main Results:

  • CDNVs exhibited higher production yields compared to EVs and a broader protein composition.
  • In vitro and in vivo studies revealed no detrimental effects or toxicity associated with CDNVs.
  • Efficient loading of RNA and proteins into CDNVs was achieved, alongside successful surface protein engineering.
  • Engineered CDNVs with enhanced PD1 expression demonstrated immunomodulatory effects, including enhanced NK and T cell degranulation and increased tumor cell death.

Conclusions:

  • CDNVs are a viable, high-yield alternative to natural EVs with a favorable safety profile.
  • CDNVs can be effectively loaded with therapeutic payloads and engineered for enhanced functionality.
  • Engineered CDNVs show significant promise for targeted drug delivery and cancer immunotherapy through enhanced immunomodulation.