Tumor Abnormality-Oriented Nanomedicine Design

Chemical Reviews, Год журнала: 2023, Номер 123(18), С. 10920 - 10989

Опубликована: Сен. 15, 2023

Anticancer nanomedicines have been proven effective in mitigating the side effects of chemotherapeutic drugs. However, challenges remain augmenting their therapeutic efficacy. Nanomedicines responsive to pathological abnormalities tumor microenvironment (TME) are expected overcome biological limitations conventional nanomedicines, enhance efficacies, and further reduce effects. This Review aims quantitate various TME, which may serve as unique endogenous stimuli for design stimuli-responsive provide a broad objective perspective on current understanding cancer treatment. We dissect typical transport process barriers drug delivery, highlight key principles designed tackle series delivery process, discuss "all-into-one" "one-for-all" strategies integrating needed properties nanomedicines. Ultimately, we insight into future perspectives toward clinical translation

Язык: Английский

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Autophagy inhibitors for cancer therapy: Small molecules and nanomedicines

Pharmacology & Therapeutics, Год журнала: 2023, Номер 249, С. 108485 - 108485

Опубликована: Июль 3, 2023

Язык: Английский

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Manganese-Based Immunostimulatory Metal–Organic Framework Activates the cGAS-STING Pathway for Cancer Metalloimmunotherapy

ACS Nano, Год журнала: 2023, Номер 17(16), С. 15905 - 15917

Опубликована: Авг. 11, 2023

Metal-organic frameworks (MOFs) show tremendous promise for drug delivery due to their structural and functional versatility. However, MOFs are usually used as biologically inert carriers in most cases. The creation of intrinsically immunostimulatory remains challenging. In this study, a facile green synthesis method is proposed the preparation manganese ion (Mn2+)-based MOF (ISAMn-MOF) cancer metalloimmunotherapy. ISAMn-MOF significantly facilitates activation cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) related signaling pathways bone-marrow-derived dendritic cells (BMDCs). BMDCs treated with secrete 4-fold higher type I 2- 16-fold proinflammatory cytokines than those equivalent MnCl2. alone or its combination immune checkpoint antibodies suppresses tumor growth metastasis prolongs mouse survival. Mechanistic studies indicate that treatment infiltration stimulatory tumors lymphoid organs. This study provides insight into design bioactive improved

Язык: Английский

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A Vacancy‐Engineering Ferroelectric Nanomedicine for Cuproptosis/Apoptosis Co‐Activated Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(30)

Опубликована: Май 4, 2024

Abstract Low efficacy of immunotherapy due to the poor immunogenicity most tumors and their insufficient infiltration by immune cells highlights importance inducing immunogenic cell death activating system for achieving better treatment outcomes. Herein, ferroelectric Bi 2 CuO 4 nanoparticles with rich copper vacancies (named BCO‐V Cu ) are rationally designed engineered ferroelectricity‐enhanced apoptosis, cuproptosis, subsequently evoked immunotherapy. In this structure, suppressed recombination electron–hole pairs band bending polarization lead high catalytic activity, triggering reactive oxygen species bursts apoptosis. The fragments produced apoptosis serve as antigens activate T cells. Moreover, generated charge catalysis, nanomedicine can act “a smart switch” open membrane, promote nanomaterial endocytosis, shut down + outflow pathway evoke thus a strong response is triggered reduced content adenosine triphosphate. Ribonucleic acid transcription tests reveal pathways related activation. Thus, study firstly demonstrates feasible strategy enhancing using single semiconductor‐induced cuproptosis.

Язык: Английский

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Layered Double Hydroxides: Recent Progress and Promising Perspectives Toward Biomedical Applications

Advanced Science, Год журнала: 2024, Номер 11(20)

Опубликована: Март 19, 2024

Abstract Layered double hydroxides (LDHs) have been widely studied for biomedical applications due to their excellent properties, such as good biocompatibility, degradability, interlayer ion exchangeability, high loading capacity, pH‐responsive release, and large specific surface area. Furthermore, the flexibility in structural composition ease of modification LDHs makes it possible develop specifically functionalized meet needs different applications. In this review, recent advances applications, which include LDH‐based drug delivery systems, cancer diagnosis therapy, tissue engineering, coatings, functional membranes, biosensors, are comprehensively discussed. From these various research fields, can be seen that there is great potential possibility use However, at same time, must recognized actual clinical translation still very limited. Therefore, current limitations related on discussed by combining limited examples with requirements biomaterials. Finally, an outlook future provided.

Язык: Английский

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Zinc–Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy

ACS Nano, Год журнала: 2024, Номер 18(15), С. 10542 - 10556

Опубликована: Апрель 1, 2024

Immunotherapy has emerged as a potential approach for breast cancer treatment. However, the rigid stromal microenvironment and low immunogenicity of tumors strongly reduce sensitivity to immunotherapy. To sensitize patients immunotherapy, hyaluronic acid-modified zinc peroxide–iron nanocomposites (Fe-ZnO2@HA, abbreviated FZOH) were synthesized remodel increase tumor immunogenicity. The constructed FZOH spontaneously generated highly oxidative hydroxyl radicals (·OH) that degrade acid (HA) in extracellular matrix (ECM), thereby reshaping enhancing blood perfusion, drug penetration, immune cell infiltration. Furthermore, not only triggers pyroptosis through activation caspase-1/GSDMD-dependent pathway but also induces ferroptosis various mechanisms, including increasing levels Fe2+ intracellular iron pool, downregulating expression FPN1 inhibit efflux, activating p53 signaling cause failure SLC7A11-GSH-GPX4 axis. Upon treatment with FZOH, 4T1 cells undergo both pyroptosis, exhibiting strong immunogenic response. remodeling response induced by collectively compensate limitations immunotherapy significantly enhance antitumor checkpoint inhibitor αPD-1. This study proposes perspective therapy cancer.

Язык: Английский

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Decomposable Nanoagonists Enable NIR‐Elicited cGAS‐STING Activation for Tandem‐Amplified Photodynamic‐Metalloimmunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 14, 2024

Activation of the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve therapeutic outcomes immunotherapy. However, "constantly active" mode current STING agonist delivery strategies typically leads off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized activation photodynamic-metalloimmunotherapy. The engineered enabled generation mitochondria-targeted reactive oxygen species under NIR irradiation specifically release mitochondrial DNA (mtDNA) inhibit repair nuclear via hypoxia-responsive drugs. Oxidized tumor mtDNA serves endogenous danger-associated molecular pattern that activates cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance cGAS enzymatic activity through metalloimmune effects. By combining synergistically enhanced triggered by irradiation, facilitated maturation dendritic infiltration cytotoxic T lymphocytes primary eradication, which also established long-term anti-tumor immunity suppress metastasis. Therefore, developed NIR-triggered, agonist-free, tandem-amplified pathway, thereby offering distinct paradigm

Язык: Английский

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Metal‐based smart nanosystems in cancer immunotherapy

Exploration, Год журнала: 2024, Номер 4(6)

Опубликована: Март 22, 2024

Abstract Metals are an emerging topic in cancer immunotherapy that have shown great potential modulating immunity cycle and promoting antitumor by activating the intrinsic immunostimulatory mechanisms which been identified recent years. The main challenge of metal‐assisted lies fact free metals as ion forms easily cleared during circulation, even cause systemic metal toxicity due to off‐target effects. With rapid development nanomedicine, metal‐based smart nanosystems (MSNs) with unique controllable structure become one most promising delivery carriers solve issue, owing their various endogenous/external stimuli‐responsiveness release ions for metalloimmunotherapy. In this review, state‐of‐the‐art research progress metal‐related is comprehensively summarized. First, mainstream MSNs‐assisted will be delineated. immunological effects certain categorization MSNs different characters compositions then provided, followed representative exemplar applications treatment, synergistic combination immunotherapy. Finally, we conclude review a summary remaining challenges associated provide authors' perspective on further advances.

Язык: Английский

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Lysosomal Rupture‐Mediated “Broken Window Effect” to Amplify Cuproptosis and Pyroptosis for High‐Efficiency Cancer Immunotherapy

Advanced Functional Materials, Год журнала: 2024, Номер 34(29)

Опубликована: Фев. 23, 2024

Abstract Autophagy, a lysosome‐involved degradation pathway, as self‐protective cellular process, always weakens the efficiency of tumor therapies. Herein, for first time, biodegradable copper (Cu) ions doped layered double hydroxide (Cu‐LDH) nanoparticles are reported cancer immunotherapy via lysosomal rupture‐mediated “Broken Window Effect”. Only injection Cu‐LDH single therapeutic agent achieves various organelles destruction after rupture, well abnormal aggregation Cu in cells cuproptosis and pyroptosis. More importantly, autophagy inhibition caused by rupture improves overload‐mediated pyroptosis blocking lysosome‐mediated bulk leading to good anti‐tumor immune responses ultimately high‐efficiency growth inhibition. This Effect” provides new paradigm enhanced therapy.

Язык: Английский

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Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination

Cancer Letters, Год журнала: 2024, Номер 598, С. 217079 - 217079

Опубликована: Июнь 25, 2024

Язык: Английский

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