Conquering the Hypoxia Limitation for Photodynamic Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(48)

Published: Sept. 27, 2021

Photodynamic therapy (PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due the hypoxic nature characteristic of many solid tumors, PDT is frequently limited therapeutic effect. Moreover, consumption O2 during may further aggravate tumor condition, which promotes proliferation, metastasis, invasion resulting poor prognosis treatment. Therefore, numerous efforts have been made increase content with goal enhancing efficacy. Herein, these strategies developed past decade are comprehensively reviewed alleviate hypoxia, including 1) delivering exogenous directly, 2) generating situ, 3) reducing cellular by inhibiting respiration, 4) regulating TME, (e.g., normalizing vasculature or disrupting extracellular matrix), 5) hypoxia-inducible factor 1 (HIF-1) signaling pathway relieve hypoxia. Additionally, -independent Type-I also discussed as an alternative strategy. By reviewing progress, it hoped that this review will provide innovative perspectives new nanomaterials designed combat hypoxia avoid associated limitation PDT.

Language: Английский

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Supramolecular Photosensitizer Enables Oxygen-Independent Generation of Hydroxyl Radicals for Photodynamic Therapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 4081 - 4087

Published: Feb. 13, 2023

The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop oxygen-independent supramolecular agent that produces hydroxyl radical (•OH) by oxidizing water the presence intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as electron donor and coassembled with perylene diimide acceptor form quadruple hydrogen-bonded agent. Detailed mechanism studies reveal intermolecular transfer charge separation upon light irradiation result efficient generation ion pairs. Under conditions, cationic radicals directly oxidize generate cytotoxic •OH, anionic electrons acid, realizing catalytic cycle. Thus, this exhibited superb photocytotoxicity even severe environments excellent vivo antitumor on HeLa-bearing mouse models. This work provides a strategy for constructing agents, opens up avenue effective PDT tumors.

Language: Английский

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Achieving Efficient NIR‐II Type‐I Photosensitizers for Photodynamic/Photothermal Therapy upon Regulating Chalcogen Elements

Advanced Materials, Journal Year: 2021, Volume and Issue: 34(7)

Published: Dec. 22, 2021

Second near-infrared (NIR-II) window type-I photosensitizers have intrinsic advantages in photodynamic/photothermal therapy (PDT/PTT) of some malignant tumors with deep infiltration, large size, complicated location, and low possibility surgery/radiotherapy. Herein, three chalcogen-element-based donor-acceptor-type semiconducting polymers (poly[2,2″-((E)-4,4″-bis(2-octyldodecyl)-[6,6″-bithieno[3,2-b]pyrrolylidene]-5,5″(4H,4″H)-dione)-alt-2,5-(thiophene)] (PTS), poly[2,2″-((E)-4,4″-bis(2-octyldodecyl)-[6,6″-bithieno[3,2-b]pyrrolylidene]-5,5″(4H,4″H)-dione)-alt-2,5-(selenophene)] (PTSe), poly[2,2″-((E)-4,4″-bis(2-octyldodecyl)-[6,6″-bithieno[3,2-b]pyrrolylidene]-5,5″(4H,4'H)-dione)-alt-2,5-(tellurophene)] (PTTe)) are synthesized fully characterized, demonstrating strong absorption the NIR-II region. Upon adjusting chalcogen elements, intramolecular charge-transfer characteristics heavy-atom effect tuned to enhance intersystem crossing rate, improving photodynamic effect. Moreover, energy levels Gibbs free energies facilitate process. As a result, PTTe nanoparticles (NPs) produce superoxide anion radicals (O2•- ) more efficiently demonstrate higher photothermal conversion efficiency than PTS PTSe NPs upon (1064 nm) laser irradiation, exhibiting unprecedented PDT/PTT performance vitro vivo. This work provides ideas for achieving high-performance hypoxic oncotherapy.

Language: Английский

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Acceptor Planarization and Donor Rotation: A Facile Strategy for Realizing Synergistic Cancer Phototherapy via Type I PDT and PTT

ACS Nano, Journal Year: 2022, Volume and Issue: 16(3), P. 4162 - 4174

Published: March 1, 2022

Tumor hypoxia seriously impairs the therapeutic outcomes of type II photodynamic therapy (PDT), which is highly dependent upon tissue oxygen concentration. Herein, a facile strategy acceptor planarization and donor rotation proposed to design I photosensitizers (PSs) photothermal reagents. Acceptor can not only enforce intramolecular charge transfer redshift NIR absorption but also PSs from photochemical pathways. Donor optimizes conversion efficiency (PCE). Accordingly, three 3,6-divinyl-substituted diketopyrrolopyrrole (DPP) derivatives, 2TPAVDPP, TPATPEVDPP, 2TPEVDPP, with different number rotors were prepared. Experimental results showed that compounds excellent PSs, corresponding 2TPEVDPP nanoparticles (NPs) most possessed highest PCE. The photophysical properties NPs are particularly suitable for in vivo fluorescence imaging-guided synergistic PDT/PTT therapy. helpful exploiting phototherapeutic reagents high efficacy PDT PTT.

Language: Английский

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Advances in smart mesoporous carbon nanoplatforms for photothermal–enhanced synergistic cancer therapy

Chemical Engineering Journal, Journal Year: 2022, Volume and Issue: 435, P. 134886 - 134886

Published: Jan. 29, 2022

Language: Английский

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An unexpected strategy to alleviate hypoxia limitation of photodynamic therapy by biotinylation of photosensitizers

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 25, 2022

The most common working mechanism of photodynamic therapy is based on high-toxicity singlet oxygen, which called Type II therapy. But it highly dependent oxygen consumption. Recently, I has been found to have better hypoxia tolerance ease this restriction. However, few strategies are available the design photosensitizers. We herein report an unexpected strategy alleviate limitation traditional by biotinylation three photosensitizers (two fluorescein-based and commercially Protoporphyrin). biotiylated named as compound 1, 2 3, exhibit impressive ability in generating both superoxide anion radicals oxygen. Moreover, 1 can be activated upon low-power white light irradiation with stronger generation than other two. excellent combinational / performance demonstrated 1. This work presents a universal protocol provide tumor-targeting enhance or trigger against tumor hypoxia.

Language: Английский

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BODIPY as a Multifunctional Theranostic Reagent in Biomedicine: Self‐Assembly, Properties, and Applications

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(18)

Published: Nov. 18, 2022

Abstract The use of boron dipyrromethene (BODIPY) in biomedicine is reviewed. To open, its synthesis and regulatory strategies are summarized, inspiring cutting‐edge work post‐functionalization highlighted. A brief overview assembly model BODIPY then provided: introduced as a promising building block for the formation single‐ multicomponent self‐assembled systems, including nanostructures suitable aqueous environments, thereby showing great development potential supramolecular applications. frontier progress biomedical application thereafter described, supported by examples frontiers applications BODIPY‐containing smart materials: it mainly involves materials based on blocks their assemblies fluorescence bioimaging, photoacoustic imaging, disease treatment photodynamic therapy, photothermal immunotherapy. Lastly, not only current status family field but also challenges worth considering summarized. At same time, insights into future prospects biomedically applicable provided.

Language: Английский

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Cationization-Enhanced Type I and Type II ROS Generation for Photodynamic Treatment of Drug-Resistant Bacteria

ACS Nano, Journal Year: 2022, Volume and Issue: 16(6), P. 9130 - 9141

Published: May 18, 2022

Photodynamic therapy as an emerging phototheranostic approach holds great potential for antibacterial treatment, but is limited by compromised reactive oxygen species (ROS) generation in aggregate and hypoxic microenvironment. Herein, we report a molecular cationization to boost the ROS, especially type I ROS of aggregation-induced emission (AIE) photosensitizers photodynamic treatment drug-resistant bacteria. Such reinforces electron-accepting ability cationic moiety, promotes intersystem crossing (ISC), increases electron separation transfer processes. The resultant CTBZPyI exhibits largely enhanced with predominant hydroxyl radical over its neutral counterpart aggregate. Moreover, also confers bacterial binding moderate inactivation dark. Further light irradiation leads superb performance, which healing process MRSA-infected wound. strategy expected be general design highly effective infection treatment.

Language: Английский

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The Current Status of Photodynamic Therapy in Cancer Treatment

Cancers, Journal Year: 2023, Volume and Issue: 15(3), P. 585 - 585

Published: Jan. 18, 2023

Although we have made great strides in treating deadly diseases over the years, cancer therapy still remains a daunting challenge. Among numerous anticancer methods, photodynamic (PDT), non-invasive therapeutic approach, has attracted much attention. PDT exhibits outstanding performance therapy, but some unavoidable disadvantages, including limited light penetration depth, poor tumor selectivity, as well oxygen dependence, largely limit its efficiency for solid tumors treatment. Thus, strategies gone into overcoming these obstacles, such exploring new photosensitizers with higher conversion efficiency, alleviating hypoxia to fuel generation of reactive species (ROS), designing tumor-targeted PS, and applying PDT-based combination strategies. In this review, briefly summarized related approaches, which are mainly characterized by advanced PSs, PSs excellent additional refreshing features. We also summarize therapies effects.

Language: Английский

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Supramolecular photodynamic agents for simultaneous oxidation of NADH and generation of superoxide radical

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 19, 2022

Abstract Given that Type-I photosensitizers (PSs) have hypoxia tolerance, developing general approaches to prepare PSs is of great importance, but remains a challenge. Here, we report supramolecular strategy for the preparation photodynamic agents, which simultaneously generate strong oxidizing cationic radicals and superoxide radicals, by introducing electron acceptors existing Type-II PSs. As proof-of-concept, three were designed co-assembled with classical PS produce quadruple hydrogen-bonded agents. The photo-induced transfer from adjacent acceptor occurs efficiently, leading generation +• an anionic radical acceptor, further transfers oxygen form O 2 −• . In addition, these agents induce direct photocatalytic oxidation NADH turnover frequency as high 53.7 min −1 , offers oxygen-independent mechanism damage tumors.

Language: Английский

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