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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

A Virus-Spike Tumor-Activatable Pyroptotic Agent.

Sadia Nadeem¹, Chuang Yang², Yang Du^1,3

¹Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.

Small (Weinheim an Der Bergstrasse, Germany)

|February 1, 2021

Summary

This summary is machine-generated.

A novel virus-spike tumor-activatable pyroptotic agent (VTPA) shows promise for cancer therapy. This agent specifically targets tumors, inducing pyroptosis (programmed cell death) for cancer-specific treatment in vivo.

Keywords:

cancer therapy nanostructures pyroptosis spiky surface tumor-activatable pyroptotic agents

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Area of Science:

Biomedical Engineering
Nanotechnology
Oncology

Background:

Pyroptosis is an emerging cancer treatment strategy.
Current limitations include the lack of tumor-specific and efficient pyroptotic agents for in vivo applications.

Purpose of the Study:

To develop a virus-spike tumor-activatable pyroptotic agent (VTPA) for cancer-specific therapy.
To demonstrate cancer-specific pyroptosis in vivo using a novel nanomedicine approach.

Main Methods:

Designed VTPA with an organosilica-coated iron oxide nanoparticle core and manganese dioxide protrusions.
Investigated VTPA accumulation in tumors, lysosomal rupture, and degradation by intracellular glutathione (GSH).
Assessed the synergetic activation of nucleotide binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasomes and subsequent pyroptosis induction.

Main Results:

VTPA demonstrated tumor accumulation and facilitated intracellular lysosomal rupture.
Degradation of VTPA by tumor-overexpressed GSH released Mn ions and iron oxide nanoparticles (IONPs).
Observed activation of NLRP3 inflammasomes and lactate dehydrogenase release, leading to specific pyroptotic cell death.

Conclusions:

VTPA enables structure-dependent and tumor intracellular GSH-activatable pyroptosis.
This represents the first demonstration of cancer-specific pyroptosis in vivo.
VTPA offers a novel paradigm for developing next-generation cancer-specific pyroptotic nanomedicine.