Evoking tumor associated macrophages by mitochondria-targeted magnetothermal immunogenic cell death for cancer immunotherapy

Copyright © 2022 Elsevier Ltd. All rights reserved..

Immunogenic cell death (ICD) based on endoplasmic reticulum (ER) stress has been widely studied as the fundamentals of cancer immunotherapy. However, the currently available ICD inducers are still very rare and mostly highly toxic chemotherapeutic drugs. Herein, a novel ICD modality based on mitochondrial heat stress by magnetic hyperthermia treatment (MHT), is proposed for effectively evoking tumor-associated macrophages (TAMs) against cancer cells. A monodisperse and biocompatible nanomedicine by grafting arginyl-glycyl-aspartic acid (RGD) and (3-carboxypropyl)triphenylphosphonium bromide (TPP) onto the surface of superparamagnetic ZnCoFe2O4ZnMnFe2O4 nanoparticles (MNPs), named as MNPs-RGD-TPP (MRT), was synthesized for mitochondrial heat stress-induced oxidative damage of tumor cells under the magnetothermal manipulation. Such heat stress-damaged mitochondria can cause the immunogenic death of tumor cells to release damage-associated molecular patterns (DAMPs), including ATP and HSP 70, to M1-polarize TAMs, resulting in the reactivated immunoresponse of macrophages against cancer cells. The effectiveness and robustness of MRT nanomedicine in evoking TAMs-mediated extracellular killing or phagocytosis are verified both in vitro and in vivo. Such a therapeutic approach based on mitochondria-targeted magnetothermal ICD for activating TAMs may be instructive to future anticancer immunotherapy.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:289

Enthalten in:

Biomaterials - 289(2022) vom: 01. Okt., Seite 121799

Sprache:

Englisch

Beteiligte Personen:

Jiang, Han [VerfasserIn]
Fu, Hao [VerfasserIn]
Guo, Yuedong [VerfasserIn]
Hu, Ping [VerfasserIn]
Shi, Jianlin [VerfasserIn]

Links:

Volltext

Themen:

8L70Q75FXE
Adenosine Triphosphate
Bromides
Cancer immunotherapy
Damage-associated molecular patterns
Immunogenic cell death
Journal Article
M1 polarization
Mitochondrial heat stress
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 06.10.2022

Date Revised 22.12.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.biomaterials.2022.121799

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM346687969