Mitochondrial‐Targeted CS@KET/P780 Nanoplatform for Site‐Specific Delivery and High‐Efficiency Cancer Immunotherapy in Hepatocellular Carcinoma

Advanced Science, Год журнала: 2024, Номер 11(14)

Опубликована: Фев. 2, 2024

Abstract Hepatocellular carcinoma (HCC) is a form of malignancy with limited curative options available. To improve therapeutic outcomes, it imperative to develop novel, potent modalities. Ketoconazole (KET) has shown excellent efficacy against HCC by eliciting apoptosis. However, its water solubility hampers application in clinical treatment. Herein, mitochondria‐targeted chemo‐photodynamic nanoplatform, CS@KET/P780 NPs, designed using nanoprecipitation strategy integrating newly synthesized photosensitizer (P780) and chemotherapeutic agent KET coated chondroitin sulfate (CS) amplify therapy. In this CS confers tumor‐targeted subsequently pH‐responsive drug delivery behavior binding glycoprotein CD44, leading the release P780 KET. Mechanistically, following laser irradiation, targets destroys mitochondrial integrity, thus inducing apoptosis through enhancement reactive oxygen species (ROS) buildup. Meanwhile, KET‐induced synergistically enhances anticancer effect P780. addition, tumor cells undergoing can trigger immunogenic cell death (ICD) longer‐term antitumor response releasing tumor‐associated antigens (TAAs) damage‐associated molecular patterns (DAMPs), which together contribute improved outcomes HCC. Taken together, NPs bioavailability exhibit exerting chemophototherapy immunity.

Язык: Английский

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Deep Red‐Light‐Mediated Nitric Oxide and Photodynamic Synergistic Antibacterial Therapy for the Treatment of Drug‐Resistant Bacterial Infections

Small, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Abstract Infections caused by persistent, drug‐resistant bacteria pose significant challenges in inflammation treatment, often leading to severe morbidity and mortality. Herein, the photosensitizer rhodamine derivatives are selected as light‐trapping dye electron‐rich substituent N‐nitrosoaminophen nitric oxide (NO)‐releasing component develop a multifunctional (deep) red‐light activatable NO photocage/photodynamic prodrug for efficient treatment of wounds diabetic foot infections. The prodrug, RhB‐NO‐2 integrates antimicrobial photodynamic therapy (aPDT), sterilization, NO‐mediated anti‐inflammatory properties within small organic molecule is capable releasing generating Reactive oxygen species (ROS) when exposed red laser (660 nm). This strategy overcomes limitation using single photosensitizer, which inadequate eliminating bacteria. Additionally, it demonstrates that released from can interact with superoxide anions (O 2 •− ) generated PDT form more reactive oxidative agent, peroxynitrite (ONOO − ). These three components act synergistically enhance effects. Furthermore, inhibit NF‐κB pathway regulating expression toll‐like receptor (TRL2) tumor necrosis factor‐α (TNF‐α), thereby alleviating tissue inflammation. developed ， has potential expedite healing superficial infected offer promising approach treating ulcers (DFUs).

Язык: Английский

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A Smart Visualized Phototherapy Switch: From NIR‐I Imaging‐Guided Photodynamic Therapy to NIR‐II‐Guided Photothermal Therapy for Enhanced Cascade Tumor Photoablation

Aggregate, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

ABSTRACT Imaging‐guided phototherapy holds promise for precision cancer treatment. However, most photosensitizers have only a singular modality of photodynamic therapy (PDT) or photothermal (PTT), which make their therapeutic efficacy severely limited by the hypoxic and complex tumor microenvironment (TME). In this article, we provide smart platform design (BOD‐D) based on visualized light‐triggered phototherapeutic switch transforming from near‐infrared (NIR)‐I imaging‐guided PDT to activatable NIR‐II‐guided PTT while releasing nitric oxide (NO) gas (GT). BOD‐D releases native NIR one‐region fluorescence signals in tumors, is used direct robust killing. As administered, decreasing oxygen content TME becomes progressively insufficient maintain its excellent cell‐killing effect. Subsequently, light triggers dissociation NO BOD‐D, activating agent BOD‐T that emits NIR‐II fluorescence, subsequent PTT. Notably, not light‐mediated mechanism can be switched NIR‐I‐guided PTT, but also released during process will GT sensitize above Our study contributes intelligent cascade photoablation.

Язык: Английский

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Self‐Assembly of H₂S‐Generating Photosensitizer for Gas‐Assisted Synergistic Photothermal Therapy

Small, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Photothermal therapy (PTT) is emerging as a promising cancer treatment, but uneven heat distribution increases side effects and reduces treatment precision, where high-temperature zones risk inducing undesired inflammation, while low-temperature regions are insufficient due to upregulation of shock proteins (HSPs). Herein, gas-assisted PTT strategy designed link near-infrared heptamethine cyanine (Cy7) with self-immolative phenyl thiocarbonate (PTC), hydrogen sulfide (H2S) donor through disulfide bond, creating small-molecule photosensitizer (Cy7-SS-PTC) that can self-assemble into nanoparticles (NPs) without stabilizers. Upon internalized by cells, Cy7-SS-PTC NPs respond elevated glutathione levels, simultaneously release Cy7 H2S via cascade reaction. The released reassembles nanoaggregates, generating hyperthermia under 808 nm light irradiation, then binds albumin, producing strong fluorescence track tumors for precise treatment. not only disrupts the mitochondrial respiratory chain, blocks ATP production, suppresses HSP70 overexpression amplify efficacy also curbs proinflammatory cytokines in zones, delivering powerful tumor ablation minimal inflammation. This small-molecule-based "H2S-assisted PTT" optimizes current validates its potential clinical application.

Язык: Английский

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Engineering of phytic acid-coated Prussian nanoparticles for combined Nitric oxide and Low-Temperature photothermal therapy of osteosarcoma

Chemical Engineering Journal, Год журнала: 2024, Номер 491, С. 151730 - 151730

Опубликована: Апрель 27, 2024

Язык: Английский

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Supramolecular dye nanoassemblies for advanced diagnostics and therapies

Bioengineering & Translational Medicine, Год журнала: 2024, Номер 9(4)

Опубликована: Фев. 13, 2024

Abstract Dyes have conventionally been used in medicine for staining cells, tissues, and organelles. Since these compounds are also known as photosensitizers (PSs) which exhibit photoresponsivity upon photon illumination, there is a high desire towards formulating molecules into nanoparticles (NPs) to achieve improved delivery efficiency enhanced stability novel imaging therapeutic applications. Furthermore, it has shown that some of the photophysical properties can be altered NP formation thereby playing major role outcome their application. In this review, we primarily focus on introducing dye categories, formulation strategies how affect context photothermal non‐photothermal More specifically, most recent progress showing potential supramolecular assemblies modalities such photoacoustic fluorescence imaging, photodynamic therapies well employment photoablation modality will outlined. Aside from activity, delve shortly emerging application dyes drug stabilizing agents where together with aggregator form stable nanoparticles.

Язык: Английский

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Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under NIR‐II Fluorescence Imaging

Advanced Science, Год журнала: 2024, Номер 11(33)

Опубликована: Март 19, 2024

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due invisible small satellite lesions and blurry boundaries. Besides, intraoperative frozen-section analysis resection margins OS often restricted by hard tissues around OS, which makes it impossible know whether negative achieved. Any unresected residuals will lead local recurrence worse prognosis. Herein, based on high expression B7H3 in targeted probe B7H3-IRDye800CW synthesized conjugating anti-B7H3 antibody IRDye800CW. can accurately label areas after intravenous administration, thereby helping surgeons identify resect residual (<2 mm) lung metastatic lesions. The tumor-background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human specimen B7H3-IRDye800CW, specifically area even microinvasion (confirmed hematoxylin-eosin [HE] staining). labeled consistent shown magnetic resonance imaging complete HE staining specimen. In summary, has translational potential guidance rapid pathological diagnosis OS.

Язык: Английский

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Catalytic Biomaterials‐Activated In Situ Chemical Reactions: Strategic Modulation and Enhanced Disease Treatment

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Abstract Chemical reactions underpin biological processes, and imbalances in critical biochemical pathways within organisms can lead to the onset of severe diseases. Within this context, emerging field “Nanocatalytic Medicine” leverages nanomaterials as catalysts modulate fundamental chemical specific microenvironments This approach is designed facilitate targeted synthesis localized accumulation therapeutic agents, thus enhancing treatment efficacy precision while simultaneously reducing systemic side effects. The effectiveness these nanocatalytic strategies critically hinges on a profound understanding kinetics intricate interplay particular pathological ensure effective catalytic actions. review methodically explores situ their associated biomaterials, emphasizing regulatory that control responses. Furthermore, discussion encapsulates crucial elements‐reactants, catalysts, reaction conditions/environments‐necessary for optimizing thermodynamics reactions, rigorously addressing both biophysical dimensions disease enhance outcomes. It seeks clarify mechanisms underpinning biomaterials evaluate potential revolutionize across various conditions.

Язык: Английский

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Sustained Release of Nitric Oxide‐Mediated Angiogenesis and Nerve Repair by Mussel‐Inspired Adaptable Microreservoirs for Brain Traumatic Injury Therapy

Advanced Healthcare Materials, Год журнала: 2023, Номер unknown

Опубликована: Сен. 15, 2023

Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering tissue repair. This process is exacerbated by the accumulation of activated immunocytes at site, which contributes to scar formation impedes In this study, a mussel-inspired nitric oxide-release microreservoir (MINOR) that combines features reactive oxygen species (ROS) scavengers sustained NO release promote angiogenesis neurogenesis developed for TBI therapy. The injectable MINOR fabricated using microfluidic device exhibits excellent monodispersity gel-like self-healing properties, allowing maintenance its structural integrity functionality upon injection. Furthermore, polydopamine in enhances cell adhesion, significantly reduces ROS levels, suppresses inflammation. Moreover, oxide (NO) donor embedded into enables NO, facilitating mitigating responses. By harnessing these synergistic effects, biocompatible demonstrates remarkable efficacy enhancing recovery mice. These findings benefit future therapeutic interventions patients with TBI.

Язык: Английский

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In situ engineered magnesium alloy implant for preventing postsurgical tumor recurrence

Bioactive Materials, Год журнала: 2024, Номер 40, С. 474 - 483

Опубликована: Июнь 26, 2024

Invasive tumors are difficult to be completely resected in clinical surgery due the lack of clear resection margins, which greatly increases risk postoperative recurrence. However, chemotherapy and radiotherapy as traditional means adjuvant therapy, limited applications, such multi-drug resistance low sensitivity, etc. Therefore, an engineered magnesium alloy rod is designed a implant remove residual tumor tissue inhibit recurrence by gas mild magnetic hyperthermia therapy (MMHT). As reactive metal, responds acidic microenvironment continuously generating hydrogen. The in-situ generation hydrogen not only protects surrounding normal tissue, but also enables achieve MMHT under low-intensity alternating field (AMF). Furthermore, numerous oxygen species (ROS) produced heat stress will combine with nitric oxide (NO) generated situ, produce more toxic nitrogen (RNS) storm. In summary, can RNS storm AMF, biodegradability makes great potential for application.

Язык: Английский

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