Dual‐Responsive Supramolecular Polymeric Nanomedicine for Self‐Cascade Amplified Cancer Immunotherapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(20)

Published: March 17, 2024

Abstract Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death is accompanied by checkpoint inhibitors, can induce effective immunogenic long‐term activation. Therapeutic strategies to jointly pyroptosis reverse immunosuppressive microenvironments are promising for cancer immunotherapy. In this regard, dual‐responsive supramolecular polymeric nanomedicine (NCSNPs) self‐cascade amplify the benefits immunotherapy designed. The NCSNPs formulated β‐cyclodextrin coupling nitric oxide (NO) donor, activator, NLG919, an indoleamine 2,3‐dioxygenase (IDO) inhibitor, self‐assembled through host–guest molecular recognition hydrophobic interaction obtain nanoparticles. possess excellent accumulation bioavailability attributed ingenious engineering. study not only confirms occurrence NO‐triggered first time but also reverses microenvironment sites via IDO inhibitor enhancing infiltration cytotoxic T lymphocytes, achieve remarkable inhibition proliferation. Thus, provides novel strategy

Language: Английский

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A Cascade-Amplified Pyroptosis Inducer: Optimizing Oxidative Stress Microenvironment by Self-Supplying Reactive Nitrogen Species Enables Potent Cancer Immunotherapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(26), P. 16967 - 16981

Published: June 18, 2024

Selective generation of sufficient pyroptosis inducers at the tumor site without external stimulation holds immense significance for a longer duration immunotherapy. Here, we report cascade-amplified inducer CSCCPT/SNAP that utilizes reactive nitrogen species (RNS), self-supplied from diffusion-controlled reaction between oxygen (ROS) and nitric oxide (NO) to potentiate immunotherapy, while both endogenous mitochondrial ROS stimulated by released camptothecin NO initiate pyroptosis. Mechanistically, cascade amplification antitumor immune response is prompted cooperation enhanced RNS with long lifetime, which could be used as trigger effectively compensate inherent drawbacks ROS, resulting in long-lasting favoring Tumor growth efficiently inhibited mouse melanoma tumors through facilitation oxygen/nitrogen (RONS)-NO synergy. In summary, our therapeutic approach supramolecular engineering nanotechnology integrate producers donors tumor-specific stimulus responses into system guarantees synchronous these two elicit pyroptosis-evoked response, using amplifier. RONS-NO synergy achieves sustained robust cancer

Language: Английский

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Reprogramming Dysfunctional Dendritic Cells by a Versatile Catalytic Dual Oxide Antigen-Captured Nanosponge for Remotely Enhancing Lung Metastasis Immunotherapy

ACS Nano, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

Dendritic cells (DCs) play a crucial role in initiating antitumor immune responses. However, the tumor environment, dendritic often exhibit impaired antigen presentation and adopt an immunosuppressive phenotype, which hinders their function reduces ability to efficiently present antigens. Here, dual catalytic oxide nanosponge (DON) doubling as remotely boosted catalyst inducer of programming DCs program therapy is reported. Intravenous delivery DON enhances accumulation via marginated target. At site, incorporates cerium nanozyme (CeO

Language: Английский

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Anion exchange regulated charge separation engineering in bismuth nanoflowers for sonocatalytic radio-immunotherapy

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: 687, P. 801 - 816

Published: Feb. 17, 2025

Language: Английский

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Supramolecular Modulation of Tumor Microenvironment Through Host−Guest Recognition and Metal Coordination to Potentiate Cancer Chemoimmunotherapy

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract The massive amount of indoleamine 2,3‐dioxygenase 1 (IDO‐1) in tumor cells and tumor‐associated immune forms a feedback loop that maintains immunosuppressive microenvironment (ITM) causes escape, resulting the poor prognosis platinum chemotherapeutics. However, effective systemic administration drugs IDO‐1 inhibitors is strictly limited by their distinct chemical construction, different pharmacokinetic profiles, heterogeneous distributions. Herein, novel supramolecular method with capability to modulate proposed aiming at potentiating antitumor efficacy chemoimmunotherapy. Profiting from dynamic reversible merits noncovalent interactions, inhibitor (IDOi) 1,2‐diaminocyclohexane‐platinum(II) (DACHPt) are tailor‐encapsulated into nanoparticles (SNPs) aid host−guest recognition metal coordination, respectively, effectively increasing drug loading improving pharmacokinetics. In addition authorized chemotherapeutical effect, DACHPt performs response, which further magnified IDOi‐reversed ITM encourage T lymphocyte infiltration, guaranteeing long‐term responses improve cancer prognosis.

Language: Английский

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Fluoroalkane Engineered Magnetic Vectors Unlock the Potential of Gasdermin in Vivo Delivery for Pyroptosis Induced Cancer Therapy

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Pyroptosis, a programmed necrotic cell death mediated by gasdermin, can activate strong immune responses and serve as potential target for cancer therapy. Nevertheless, the relatively large molecular size negative surface charge of gasdermin impede them from effectively intracellular delivery directly inducing pyroptosis. Here, cytosolic protein system, fluorinated iron oxide nanoparticles (FIONPs) is reported, which self‐assemble with active A3 (GSDMA3) via noncovalent interactions trigger pyroptosis in 4T1 cells. It proved that system versatile various cargo proteins (ribonuclease A, saporin, β‐galactosidase, bovine serum albumin) different isoelectric points weights, without compromising their biological activity vitro. What's more, under magnetic drive, FIONPs facilitate transport GSDMA3 vivo, further augmenting tumor suppression response. Overall, magnetic‐driven provide an effective transductions, application reveals direct significantly elicits robust antitumor immunity induction

Language: Английский

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NIR‐II D–A–D‐Type Small‐Molecule Coordination with Carboxylatopillar[5]Arene: a Multifunctional Phototheranostic for Low‐Temperature NIR‐II Photothermal/Platinum‐Based/Chemodynamic Combination Cancer Immunotherapy

Small, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Low‐temperature second near‐infrared region (NIR‐II) photothermal therapy (PTT) has shown significant potential in minimizing damage to normal tissues and reducing inflammation. However, it still faces challenge of insufficient immune response. Thus, a multifunctional phototheranostic nanoparticle (BDPB/Pt/Fe@P[5]) is developed by co‐loading BDPB, CDHPt, Fe 2 ⁺ with pH‐sensitive lipid DSPE‐PEOz2K. The carboxylatopillar[5]arene (CP[5]) used construct this exhibits strong host–guest recognition pyridine salts, alleviating aggregation caused quench (ACQ) effect enhancing the NIR‐II emission donor–acceptor–donor (D–A–D)‐type organic small molecule (BDPB). CP[5] provides suitable vehicles for encapsulating platinum (IV) prodrugs (CDHPt) ions via metal coordination controllable reactive oxygen species (ROS) release. Under low‐intensity laser irradiation an acidic tumor microenvironment, nanoparticles degrade, releasing CDHPt platinum‐based chemodynamic (CDT). facilitates direct production superoxide anions (O₂·⁻) from O₂ partially converts into highly cytotoxic hydroxyl radicals, thereby promoting Fenton reaction process. therapeutic efficacy further synergized immunogenic cell death (ICD) effect.

Language: Английский

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Amplification of cGAS-STING Pathway with “Single-molecule Multitarget” Nanoparticles for Chemo-immunotherapy of Ovarian Cancer

Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123434 - 123434

Published: May 1, 2025

Language: Английский

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Anthracene‐Based Endoperoxides as Self‐Sensitized Singlet Oxygen Carriers for Hypoxic‐Tumor Photodynamic Therapy

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Abstract Singlet oxygen is a crucial reactive species (ROS) in photodynamic therapy (PDT). However, the hypoxic tumor microenvironment limits production of cytotoxic singlet through light irradiation PDT photosensitizers (PSs). This restriction poses major challenge improving effectiveness PDT. To overcome this challenge, researchers have explored development carriers that can capture and release physiological conditions. Among these developments, anthracene‐based endoperoxides, initially discovered almost 100 years ago, shown ability to generate controllably under thermal or photo stimuli. Recent advancements led new class self‐sensitized anthracene‐endoperoxides, with potential applications enhancing effects for tumors. review discusses current research progress utilizing anthracene‐endoperoxides as improved It covers anthracene‐conjugated small organic molecules, metal–organic complexes, polymeric structures, other nano‐structures. The molecular structural designs, mechanisms, characteristics systems will be discussed. aims provide valuable insights developing high‐performance hypoxic‐tumor

Language: Английский

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Porous Fe/Cu Nanoreactor with Dual Insurance Design for Precision Chemotherapy and Chemodynamic Therapy

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Abstract Poor prognosis and chemotherapy response stem from difficulties in precise targeting the lack of effective synergistic treatments. Nanozymes show promising potential tumor chemodynamic therapy (CDT) by catalyzing hydrogen peroxide (H₂O₂) decomposition glutathione depletion microenvironment (TME). However, integrating with CDT remains challenging. In this study, a porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) is developed for co‐loading humanized 3F8 anti‐GD2 disialoganglioside antibody (3F8) novel pyridazinone‐based chemotherapeutic agent (IMB), forming nanoreactor (3F8@FeCuNPs@IMB) targeted CDT. The responds specifically to acidic TME as primary insurance, allowing controlled release IMB at site. coating on surface acts secondary minimizing drug leakage during delivery process ensuring chemotherapy. Furthermore, FeCuNPs act peroxidase‐like (POD) oxidase‐like (GSHOX) enzymes, hydroxyl radical (•OH) generation depleting excess GSH, enhancing results vitro vivo indicate that dual insurance designed 3F8@FeCuNPs@IMB offers prospect targeted, precise, combination against melanoma.

Language: Английский

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