Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy

The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/[email protected]) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen-irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immunogenicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was obtained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release.

Abstract licence: CC BY-NC-ND

1. 11.

   PD‐L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy · 2016

2. 15.
   Retracted

   Synthesis and Optimization of MoS 2 @Fe 3 O 4 ‐ICG/Pt(IV) Nanoflowers for MR/IR/PA Bioimaging and Combined PTT/PDT/Chemotherapy Triggered by 808 nm Laser · 2017

3. 26.

   The Landscape of Targeted Therapies in TNBC · 2020

4. 31.

   Exosome-based immunotherapy: a promising approach for cancer treatment · 2020

36 more references, whose wording the paper’s licence keeps private.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.