Overcoming barriers in photodynamic therapy harnessing nano-formulation strategies

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(16), P. 9152 - 9201

Published: Jan. 1, 2021

Photodynamic therapy (PDT) has been extensively investigated for decades tumor treatment because of its non-invasiveness, spatiotemporal selectivity, lower side-effects, and immune activation ability.

Language: Английский

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High-Performance Self-Cascade Pyrite Nanozymes for Apoptosis–Ferroptosis Synergistic Tumor Therapy

ACS Nano, Journal Year: 2021, Volume and Issue: 15(3), P. 5735 - 5751

Published: March 11, 2021

As next-generation artificial enzymes, nanozymes have shown great promise for tumor catalytic therapy. In particular, their peroxidase-like activity has been employed to catalyze hydrogen peroxide (H2O2) produce highly toxic hydroxyl radicals (•OH) kill cells. However, limited by the low affinity between with H2O2 and level of in microenvironment, peroxidase usually produced insufficient •OH cells therapeutic purposes. Herein, we present a pyrite nanozyme ultrahigh affinity, resulting 4144- 3086-fold increase compared that classical Fe3O4 natural horseradish peroxidase, respectively. We found also possesses intrinsic glutathione oxidase-like activity, which catalyzes oxidation reduced accompanied generation. Thus, dual-activity constitutes self-cascade platform generate abundant deplete glutathione, induces apoptosis as well ferroptosis Consequently, it killed apoptosis-resistant harboring KRAS mutation inducing ferroptosis. The exhibited favorable tumor-specific cytotoxicity biodegradability ensure its biosafety. These results indicate high-performance is an effective reagent may aid development nanozyme-based

Language: Английский

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Transformable Nanosensitizer with Tumor Microenvironment‐Activated Sonodynamic Process and Calcium Release for Enhanced Cancer Immunotherapy

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(25), P. 14051 - 14059

Published: April 2, 2021

Abstract Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate generation reactive oxygen species (ROS) against tumors, potentially leading off‐target toxicity normal tissues. We report a transformable core‐shell nanosonosensitizer (TiO 2 @CaP) that reinvigorates ROS and dissolves its CaP shell release Ca 2+ an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO @CaP acts as smart specifically induces mitochondrial dysfunction via overloading intracellular ions synergize with process TME. substantially enhances immunogenic cell death, resulting enhanced T‐cell recruitment infiltration into cold (4T1). In conjunction checkpoint blockade therapy (anti‐PD 1), @CaP‐mediated elicits systemic antitumor immunity, regression non‐treated distant tumors inhibition lung metastasis. This work paves way development “smart” TME‐activatable temporospatial control over responses.

Language: Английский

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A Polymer Multicellular Nanoengager for Synergistic NIR‐II Photothermal Immunotherapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(14)

Published: Feb. 26, 2021

Abstract Cell‐membrane‐coated nanoparticles (CCNPs) that integrate the biophysiological advantages of cell membranes with multifunctionalities synthetic materials hold great promise in cancer immunotherapy. However, strategies have yet to be revealed further improve their immunotherapeutic efficacy. Herein, a polymer multicellular nanoengager (SPNE) for synergistic second‐near‐infrared‐window (NIR‐II) photothermal immunotherapy is reported. The consists an NIR‐II absorbing as core, which camouflaged fused derived from immunologically engineered tumor cells and dendritic (DCs) vaccine shell. In association high accumulation lymph nodes tumors, engagement ability SPNE enables effective cross‐interactions among cells, DCs, T leading augmented activation relative bare or tumor‐cell‐coated nanoparticles. Upon deep‐tissue penetrating photoirradiation, eradicates induces immunogenic death, eliciting anti‐tumor immunity. Such effect eventually inhibits growth, prevents metastasis procures immunological memory. Thus, this study presents general cell‐membrane‐coating approach develop photo‐immunotherapeutic agents therapy.

Language: Английский

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Multienzyme-like Reactivity Cooperatively Impairs Glutathione Peroxidase 4 and Ferroptosis Suppressor Protein 1 Pathways in Triple-Negative Breast Cancer for Sensitized Ferroptosis Therapy

ACS Nano, Journal Year: 2022, Volume and Issue: 16(2), P. 2381 - 2398

Published: Jan. 18, 2022

Ferroptosis is a recently discovered route of regulated cell death that offers the opportunities for treatment chemotherapy-resistant tumor indications, but its efficacy can be affected by glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) antioxidant mechanisms, posing significant challenges clinical translation. In this study, we report Cu-tetra(4-carboxyphenyl)porphyrin chloride(Fe(III)) (Cu-TCPP(Fe)) metal organic framework (MOF)-based nanosystem efficient incorporation Au nanoparticles (NPs) RSL3, which demonstrate enzyme-like activities to universally suppress antiferroptotic pathways in cells amplifying ferroptotic damage. Herein, Cu-TCPP(Fe) MOF nanosheets were integrated with NPs via situ nucleation loaded RSL3 π–π stacking, eventually modified polyethylene glycol (PEG) iRGD tumor-targeted drug delivery. Specifically, glucose oxidase-like depletion, thus disrupting pentose phosphate pathway impede reduced (GSH) biosynthesis prevent recycling coenzyme Q10 (CoQ10) CoQ10H2, while Cu species oxidize GSH into oxidized (GSSG). These nanocatalytic lead simultaneous inhibition GPX4/GSH FSP1/CoQ10H2 cooperate GPX4-deactivating function cause pronounced damage, thereby providing strong rationale application therapy clinic.

Language: Английский

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Good Steel Used in the Blade: Well‐Tailored Type‐I Photosensitizers with Aggregation‐Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy

Advanced Science, Journal Year: 2021, Volume and Issue: 8(14)

Published: May 21, 2021

Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration distinctive strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, precise nuclear targeting protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics fabricated first time. Of two synthesized AIE PSs, TTFMN demonstrated exhibit superior property stronger reactive species (ROS) generation efficiency owing introduction tetraphenylethylene smaller singlet-triplet energy gap, respectively. With aid lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k-poly(ethylene glycol)5k-succinic anhydride-modified TAT, corresponding TTFMN-loaded nanoparticles accompanied acid-triggered peculiarity can quickly accumulate tumor site, effectively generate ROS region suppress growth under white light irradiation minimized systematic toxicity. This delicate "Good Steel Used Blade" tactic maximizes efficacy offers conceptual while practical paradigm optimized treatment further translational medicine.

Language: Английский

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Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(13), P. 5330 - 5350

Published: Jan. 1, 2022

This tutorial review discusses the convergence of drug delivery systems and PROTACs, surveys burgeoning PROTAC strategies, summarizes their design principles, clarifies challenges, outlooks future translational opportunities.

Language: Английский

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A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(13)

Published: Feb. 1, 2022

Abstract The immunosuppression and immune escape of current immunotherapy result in low efficacy, ferroptosis is greatly restricted by the reactive oxygen species (ROS) production efficiency. Here, for first time a “closed‐loop” therapy based on photothermal enhancement stimulated each other multifunctional nanoplatform reported. This platform composed copper silicate iron mesoporous hollow nanospheres, followed situ growth Au nanoparticles loading an adjuvant resiquimod R848. laser irradiation‐mediated heat introduction ions significantly enhance ROS generation, leading to simultaneous depletion glutathione peroxidase 4 (GPX4) (GSH). onset tumor cells thus enhanced response with immunogenic cell death (ICD) triggered, promoting dendritic (DCs) maturation T infiltration. Interferon γ (IFN‐γ) released from CD8 + downregulates expression SLC7A11 GPX4, which turn enhances expression, constituting “closed‐Loop” therapy. Importantly, this system effective both killing primary inhibiting metastasis. proposed therapeutic strategy may provide guidance design future antitumor nanoplatforms.

Language: Английский

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Pyroptosis‐Mediated Synergistic Photodynamic and Photothermal Immunotherapy Enabled by a Tumor‐Membrane‐Targeted Photosensitive Dimer

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(25)

Published: March 15, 2023

Overcoming the resistance to apoptosis and immunosuppression of tumor cells is a significant challenge in augmenting effect cancer immunotherapy. Pyroptosis, lytic programmed cell-death pathway unlike apoptosis, considered type immunogenic cell death (ICD) that can intensify ICD process cells, releasing dramatically increased tumor-associated antigens damage-associated molecular patterns promote Herein, membrane-targeted aggregation-induced emission photosensitive dimer found be able achieve highly efficient under synergistic photodynamic photothermal therapy. The efficiently produce type-I reactive oxygen species (ROS) by therapy hypoxic tissue, leading pyroptosis direct membrane damage, which further reinforced its effect. Furthermore, enhanced based on completely eliminate primary seventh day treatment also boost systemic antitumor immunity generating immune memory, demonstrated superior therapeutic effects both solid tumors metastatic when healing 4T1 mouse models with poor immunogenicity.

Language: Английский

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Second Near‐Infrared Light‐Activatable Polymeric Nanoantagonist for Photothermal Immunometabolic Cancer Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(36)

Published: July 23, 2021

Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small-molecule immunomodulators lead the off-target adverse effects insufficient therapeutic outcomes. Herein a second near-infrared (NIR-II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of reported. ASPA backbone obtained by conjugating vipadenant, an antagonist adenosine A2A receptor, onto NIR-II light-absorbing polymer via azo-based thermolabile linker. Under deep-penetrating photoirradiation, induces tumor thermal ablation subsequently immunogenic cell death, triggers cleavage linker, releases block adenosinergic pathway. Such remotely controlled regulation potentiates cytotoxic T functions while suppresses regulatory activities, leading efficient primary inhibition, pulmonary metastasis prevention, long-term immunological memory. Thereby, this work provides generic approach precise spatiotemporal immunometabolism.

Language: Английский

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