Peptide‐Appended Nanosonosensitizers Targeting Tumor Glycolysis for Synergistic Sonodynamic–Immunometabolic Therapy of Spinal‐Metastasized Tumors

Advanced Materials, Год журнала: 2023, Номер 35(42)

Опубликована: Июль 18, 2023

Despite recent advancements in cancer immunotherapy, challenges have yet to be surmounted achieve two major goals of magnifying antitumor immunity and remodeling the immunosuppressive tumor microenvironment. Here, a nanosystem (ODM-R) that integrates oxygen-deficient molybdenum oxide (ODM) nanosonosensitizers R7 peptides with metabolism regulation effects is designed fabricated for synergistic sonodynamic-immunometabolic therapy spinal-metastasized tumors. The ODM generates reactive oxygen species upon ultrasound irradiation implement sonodynamic (SDT), inducing cell apoptosis immunogenic death. attached on markedly inhibits uptake glucose excretion lactic acid cells by perturbing glycolysis process. combination SDT obstruction ODM-R guarantees satisfactory efficacy synergizing PD-L1 antibody eradicate tumors, achieving concurrent sonodynamic-triggered immune activation microenvironment remodeling. This work provides proof-of-concept boosting immunotherapy metabolic regulation.

Язык: Английский

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Biomimetic Nanoparticle with Glutathione Depletion and Amplified ROS Generation Capabilities for Synergistic Chemo-Sonodynamic Therapy in Squamous Cell Carcinomas

ACS Applied Materials & Interfaces, Год журнала: 2023, Номер 15(22), С. 27183 - 27194

Опубликована: Май 23, 2023

Nanomedicines for combining chemotherapy and sonodynamic therapy (SDT) have enormous potential in squamous cell carcinoma treatment. However, the therapeutic efficacy of noninvasive SDT is severely limited because generation reactive oxygen species (ROS) by sonosensitizers highly dependent on levels intracellular excess glutathione (GSH) tumor cells. To overcome this barrier, a red blood (RBC) membrane-camouflaged nanomedicine consisting GSH-sensitive polyphosphoester (SS-PPE) ROS-sensitive (S-PPE) was designed simultaneous delivery sonosensitizer hematoporphyrin (HMME) chemotherapeutic agent docetaxel (DTXL) effectively enhanced antitumor efficacy. In vitro vivo studies demonstrated that HMME-driven ROS under ultrasound (US) inhibited SCC7 proliferation accelerated DTXL release to further kill cells via hydrophobic-hydrophilic transition nanoparticle core. Meanwhile, disulfide bond SS-PPE consumes GSH prevent consumption. This biomimetic provides depletion amplified capabilities achieve novel synergistic chemo-SDT strategy carcinomas.

Язык: Английский

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Advancing nanotechnology for neoantigen-based cancer theranostics

Chemical Society Reviews, Год журнала: 2024, Номер 53(7), С. 3224 - 3252

Опубликована: Янв. 1, 2024

Neoantigens play a pivotal role in the field of tumour therapy, encompassing stimulation anti-tumour immune response and enhancement targeting capability. Nonetheless, numerous factors directly influence effectiveness neoantigens bolstering responses, including neoantigen quantity specificity, uptake rates by antigen-presenting cells (APCs), residence duration within microenvironment (TME), their ability to facilitate maturation APCs for activation. Nanotechnology assumes significant several aspects, facilitating release, promoting delivery cells, augmenting dendritic shielding from protease degradation, optimizing interactions between system. Consequently, development nanotechnology synergistically enhances efficacy cancer theranostics. In this review, we provide an overview sources, mechanisms neoantigen-induced evolution precision neoantigen-based nanomedicine. This encompasses various therapeutic modalities, such as immunotherapy, phototherapy, radiotherapy, chemotherapy, chemodynamic other strategies tailored augment therapeutics. We also discuss current challenges prospects application nanomedicine, aiming expedite its clinical translation.

Язык: Английский

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A NIR‐Light‐Activated and Lysosomal‐Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep‐Seated Tumors

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(37)

Опубликована: Май 22, 2024

Though platinum (Pt)-based complexes have been recently exploited as immunogenic cell death (ICD) inducers for activating immunotherapy, the effective activation of sufficient immune responses with minimal side effects in deep-seated tumors remains a formidable challenge. Herein, we propose first example near-infrared (NIR) light-activated and lysosomal targeted Pt(II) metallacycle (1) supramolecular ICD inducer. 1 synergistically potentiates immunomodulatory response via multiple-regulated approaches, involving NIR light excitation, boosted reactive oxygen species (ROS) generation, good selectivity between normal tumor cells, enhanced penetration/retention capabilities. Specifically, has excellent depth-activated ROS production (~7 mm), accompanied by strong anti-diffusion anti-ROS quenching ability. In vitro experiments demonstrate that exhibits significant cellular uptake generation cells well respective multicellular spheroids. Based on these advantages, induces more efficient an ultralow dose (i.e., 5 μM) compared clinical inducer-oxaliplatin (300 μM). vivo, vaccination further serves potent inducer through eliciting CD8

Язык: Английский

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Engineering Sonosensitizer‐Derived Nanotheranostics for Augmented Sonodynamic Therapy

Small, Год журнала: 2024, Номер 20(44)

Опубликована: Июль 6, 2024

Abstract Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising approach for deep‐seated tumors. However, the general or only utilization of SDT shows efficiency unsatisfactory treatment outcomes due to complicated tumor microenvironment (TME) process. To circumvent issues, three feasible approaches enhancing SDT‐based therapeutic effects, including sonosensitizer optimization, strategies conquering hypoxia TME, combinational are summarized, with particular focus on combination other modalities, chemodynamic therapy, photodynamic photothermal chemotherapy, starvation gas immunotherapy. In end, current challenges in tumors discussed enhanced effects provided. It envisioned that this review will provide new insight into strategic design high‐efficiency sonosensitizer‐derived nanotheranostics, thereby augmenting accelerating potential clinical transformation.

Язык: Английский

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Peptide‐Functionalized Inorganic Oxide Nanomaterials for Solid Cancer Imaging and Therapy

Advanced Materials, Год журнала: 2024, Номер 36(37)

Опубликована: Фев. 9, 2024

Abstract The diagnosis and treatment of solid tumors have undergone significant advancements marked by a trend toward increased specificity integration imaging therapeutic functions. multifaceted nature inorganic oxide nanomaterials (IONs), which boast optical, magnetic, ultrasonic, biochemical modulatory properties, makes them ideal building blocks for developing multifunctional nanoplatforms. A promising class materials that emerged in this context are peptide‐functionalized (PFIONs), demonstrated excellent performance therapy, making potential candidates advancing tumor treatment. Owing to the functionalities peptides targeting, penetration, responsiveness, well‐designed PFIONs can specifically accumulate release or agents at sites, enabling precise effective This review provides an overview recent advances use tumors, highlighting superiority as well synergistic Moreover, discusses challenges prospects depth, aiming promote intersection interdisciplinary facilitate their clinical translation development personalized diagnostic systems optimizing material systems.

Язык: Английский

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A Cancer Nanovaccine Based on an FeAl-Layered Double Hydroxide Framework for Reactive Oxygen Species-Augmented Metalloimmunotherapy

ACS Nano, Год журнала: 2024, Номер 18(11), С. 8143 - 8156

Опубликована: Март 4, 2024

The complexity and heterogeneity of individual tumors have hindered the efficacy existing therapeutic cancer vaccines, sparking intensive interest in development more effective situ vaccines. Herein, we introduce a nanovaccine for reactive oxygen species-augmented metalloimmunotherapy which FeAl-layered double hydroxide (LDH) is used as delivery vehicle with dihydroartemisinin (DHA) cargo. LDH framework acid-labile can be degraded tumor microenvironment, releasing iron ions, aluminum DHA. ions contribute to aggravated intratumoral oxidative stress injury by synergistic Fenton reaction DHA activation, causing apoptosis, ferroptosis, immunogenic cell death cells. subsequently released tumor-associated antigens adjuvant form generate robust long-term immune responses against recurrence metastasis. Moreover, Fe ion-enabled T1-weighted magnetic resonance imaging facilitate real-time therapy monitoring. This cancer-nanovaccine-mediated strategy has potential revolutionizing precision immunotherapy landscape.

Язык: Английский

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In Situ Redox of TiSe₂ Nanoplates to Excite Chemodynamic‐Enhanced Cancer Sono‐Immunotherapy

Small Structures, Год журнала: 2024, Номер 5(6)

Опубликована: Фев. 22, 2024

Different from the direct delivery of chemodynamic agents into tumor tissue for therapy (CDT), this work reports fabrication heterojunction sonosensitizers (CD/TiSe 2 ) in situ generation by responding to microenvironment (TME), realizing CDT‐enhanced sono‐immunotherapy. The redox TiSe acidic TME leads formation TiO x Se 2− containing (0), selenate, and Ti 3+ /Ti 4+ couple, which can facilitate CDT through a ‐mediated Fenton‐like reaction consume overexpressed glutathione (GSH) via GSH depletion. Moreover, ions generated process promote maturation dendritic cells, consequently activating adaptive immune responses. In another aspect, construction heterojunctions within carbon dots improves reactive oxygen species (ROS) efficiency cascaded manner, enhances sonodynamic activity amplifies performance. More importantly, ROS produced efficiently triggers immunogenic cell death synergistic based on elicitation antitumor immunity with aid an checkpoint blockade. This thus provides distinct paradigm transition metal selenide‐originated agent

Язык: Английский

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Inhalable nanoparticles with enhanced cuproptosis and cGAS–STING activation for synergistic lung metastasis immunotherapy

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(8), С. 3697 - 3710

Опубликована: Май 3, 2024

Due to the insufficient Cu

Язык: Английский

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Nanosonosensitizer Optimization for Enhanced Sonodynamic Disease Treatment

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Сен. 23, 2024

Low-intensity ultrasound-mediated sonodynamic therapy (SDT), which, by design, integrates sonosensitizers and molecular oxygen to generate therapeutic substances (e.g., toxic hydroxyl radicals, superoxide anions, or singlet oxygen) at disease sites, has shown enormous potential for the effective treatment of a variety diseases. Nanoscale play crucial role in SDT process because their structural, compositional, physicochemical, biological characteristics are key determinants efficacy. In particular, advances materials science nanotechnology have invigorated series optimization strategies augmenting efficacy nanosonosensitizers. This comprehensive review systematically summarizes, discusses, highlights state-of-the-art studies on current achievements nanosonosensitizer enhanced treatment, with an emphasis general design principles nanosonosensitizers strategies, mainly including organic inorganic Additionally, recent advancements optimized applications aimed treating various diseases, such as cancer, bacterial infections, atherosclerosis, autoimmune clarified detail. Furthermore, effects improved versatile thoroughly discussed. The concludes highlighting challenges future opportunities this rapidly evolving research field expedite its practical clinical translation application.

Язык: Английский

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