Molecular Engineering of Plasma Membrane and Mitochondria Dual‐Targeted NIR‐II AIE Photosensitizer Evoking Synergetic Pyroptosis and Apoptosis

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(5)

Published: Nov. 22, 2023

Phototherapy provides a noninvasive and spatiotemporal controllable paradigm to inhibit the evasion of programmed cell death (PCD) tumors. However, conventional photosensitizers (PSs) often induce single PCD process, resulting in insufficient photodamage severely impeding their application scopes. In this study, molecular engineering is conducted by adjusting electron donors develop an aggregation-induced NIR-II emissive PS (DPITQ) for plasma membrane mitochondria dual-targeted tumor therapy evoking synergetic pyroptosis apoptosis. DPITQ displays boosted type I II reactive oxygen species generation as well high photothermal conversion efficacy (43%) after laser irradiation 635 nm. The excellent biocompatibility appropriate lipophilicity help specifically anchor cancer cells. Furthermore, photosensitized can disrupt intact cause mitochondrial dysfunction, ultimately causing concurrent apoptosis suppress proliferation even under hypoxia. It noteworthy that nanoparticles (NPs) present clear fluorescence imaging capability on venous vessels nude mice. Notably, NPs exert efficient imaging-guided phototherapy both multicellular spheroids vivo, maximum destruction tumors but minimum adverse effects normal tissue.

Language: Английский

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Mitochondria-targeted fluorophores for in vivo NIR-II imaging-guided PDT/PTT

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(52), P. 8127 - 8130

Published: Jan. 1, 2023

A simple yet powerful D-A type-based NIR-II fluorophore (MTF) with mitochondria targeting was constructed. This mitochondrial dye MTF exhibited not only a photothermal effect but also photodynamic performance, and further fabricated DSPE-mPEG to generate nanodots for in vivo experiments, achieving strong fluorescence tracing of tumors impressive image-guided therapy (PDT) (PTT).

Language: Английский

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Hemicyanine-Based Type I Photosensitizers for Antihypoxic Activatable Photodynamic Therapy

ACS Materials Letters, Journal Year: 2023, Volume and Issue: 5(11), P. 3058 - 3067

Published: Oct. 20, 2023

Type I photosensitizers provide great potential for effective antihypoxia cancer treatment because of their low O2 reliance. To achieve tumor specificity, activatable type that can selectively respond to tumor-related stimuli and thereafter activate phototoxicity are urgently required, which however rare. We herein report a hemicyanine-based scaffold with photoreactions antihypoxic PDT against tumors. The common hemicyanine (Cy) endows minimized ROS generation, be nicely tuned boost production by introducing the halogens increase spin–orbit coupling (SOC) constant thus favor intersystem crossing (ISC) rate. optimized CyBr is further modified an probe (CyBrP) specifically unlock its fluoro-photoacoustic signals upon interaction alkaline phosphatase (ALP) overexpressed in By virtue high sensitivity selectivity toward ALP as well O2-dependence CyBrP allows precise phototheranostics tumors, leading effectively suppressed growth living mice. Therefore, this study presents facile halogen-substituted strategy construct serve universal scaffolds PDT.

Language: Английский

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Mitochondrial Disruption Nanosystem Simultaneously Depressed Programmed Death Ligand-1 and Transforming Growth Factor-β to Overcome Photodynamic Immunotherapy Resistance

ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 3331 - 3348

Published: Jan. 16, 2024

Currently, limited photosensitizers possess the capacity to reverse tumor hypoxia and reduce programmed death ligand-1 (PD-L1) transforming growth factor-β (TGF-β) expression simultaneously, hindering perfect photodynamic therapy (PDT) effect due acquired immune resistance hypoxic microenvironment. To tackle these challenges, in this research, we demonstrated that mitochondrial energy metabolism depression can be utilized as an innovative efficient approach for reducing of PD-L1 TGF-β which may offer a design strategy more ideal PDT nanosystem. Through proteomic analysis 5637 cells, revealed tamoxifen (TMX) incredibly regulate cells. Then, selectively deliver clinically used depressant TMX solid tumors well nanosystem, synthesized MHI-TMX@ALB by combining mitochondria-targeted heptamethine cyanine PDT-dye MHI with through self-assembly albumin (ALB). Interestingly enough, nanoparticle effective reversion inhibition protein at lower dosage (7.5 times TMX), then enhanced efficacy immunotherapy via enhancing T-cell infiltration. Apart from this, leveraging dye's targeting toward TMX's role suppressing TGF-β, also effectively mitigated 4T1 lung metastasis development. All all, could multifunctional economical codepression immune-regulating strategy, broadening potential clinical applications

Language: Английский

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Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(9)

Published: Feb. 21, 2024

Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal the photocatalyst lutetium texaphyrin (

Language: Английский

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