Photo-Amplified Plasma Membrane Rupture by Membrane-Anchoring NIR-II Small Molecule Design for Improved Cancer Photoimmunotherapy.

Angew Chem Int Ed Engl

State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu Key Laboratory for Biosensors, Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.

Published: October 2024

Immunotherapy is a promising cancer treatment method for eradicating tumor cells by enhancing the immune response. However, there are several major obstacles to conventional phototherapy-mediated immune responses, including inadequate immunogenicity and immunosuppressive environment. Here, we present a novel photoimmunotherapy modality-the development of membrane-anchoring small molecule inducing plasma membrane rupture (PMR) by NIR-II photo-stimulation, thus evoking cell necrotic death and enhancing antitumor immunotherapy. Our top-performing membrane-anchoring small molecule (CBT-3) exhibits temperature-tunable PMR efficiency, allowing rapid necrotic death in cancer cells at 50 μM dose by using exogenous NIR-II light-mediated mild photothermal effect (1064 nm, 0.6 W cm). Further evidence indicated that this gentle therapeutic approach activated inflammatory signaling pathways in cells, enhanced immunogenic cell death, and reshaped the immunosuppressive tumor microenvironment, ultimately promoting systemic antitumor immune responses in vivo. This study represents the first instance of utilizing NIR-II photo-amplified PMR effect based on membrane-anchoring small molecule, providing a novel avenue for advancing cancer photoimmunotherapy.

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202418081DOI Listing

Publication Analysis

Top Keywords

small molecule
16
membrane-anchoring small
12
plasma membrane
8
membrane rupture
8
cancer photoimmunotherapy
8
immune responses
8
necrotic death
8
photo-amplified plasma
4
membrane-anchoring
4
rupture membrane-anchoring
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!