Pillararene‐Based Stimuli‐Responsive Supramolecular Delivery Systems for Cancer Therapy

Advanced Materials, Год журнала: 2024, Номер 36(16)

Опубликована: Янв. 11, 2024

Cancer poses a significant challenge to global public health, seriously threatening human health and life. Although various therapeutic strategies, such as chemotherapy (CT), radiotherapy, phototherapy, starvation therapy, are applied cancer treatment, their limited effect, severe side effects, unsatisfactory drug release behavior need be carefully considered. Thus, there is an urgent develop efficient delivery strategies for improving treatment efficacy realizing on-demand delivery. Notably, pillararenes, emerging class of supramolecular macrocycles, possess unique properties highly tunable structures, superior host-guest chemistry, facile modification, good biocompatibility, which widely used in therapy achieve controllable reduce the toxic effects on normal tissues under internal/external stimuli conditions. This review summarizes recent advance stimuli-responsive systems (SDSs) based pillararenes tumor from perspectives different assembly methods hybrid materials, including molecular-scale SDSs, nano self-assembly systems, nanohybrid SDSs. Moreover, prospects critical challenges SDSs also discussed.

Язык: Английский

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Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(20), С. 13805 - 13816

Опубликована: Март 29, 2024

Cuproptosis, a copper-dependent cell death process, has been confirmed to further activate the immune response and mediate resistance. However, hypoxic tumor microenvironment hampers cuproptosis sensitivity suppresses body's antitumor response. Herein, we have successfully immobilized functionalized catalase (CAT) with long single-stranded DNA containing polyvalent CpG sequences through rolling circle amplification (RCA) techniques, obtaining an enzyme-cored spherical nucleic acid nanoplatform (CAT-ecSNA-Cu) deliver copper ions for cuproptosis. The presence of long-stranded DNA-protected CAT enhances mitochondrial respiration by catalyzing conversion H2O2 O2, thereby sensitizing Meanwhile, increased oxygenation expression hypoxia-inducible factor-1 (HIF-1) protein, resulting in alleviation immunosuppressive microenvironment. Of note, induces immunogenic (ICD), which facilitates dendritic (DC) maturation antigen presentation polyCpG-supported Toll-like receptor 9 (TLR9) activation. Furthermore, cuproptosis-induced PD-L1 upregulation cells complements checkpoint blockers (αPD-L1), enhancing immunity. strategy cuproptosis-mediated responses alleviating hypoxia effectively promotes activation proliferation effector T cells, ultimately leading long-term immunity against cancer.

Язык: Английский

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Redox‐Active Ferrocene Quencher‐Based Supramolecular Nanomedicine for NIR‐II Fluorescence‐Monitored Chemodynamic Therapy

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(10)

Опубликована: Дек. 18, 2023

Real-time monitoring of hydroxyl radical (⋅OH) generation is crucial for both the efficacy and safety chemodynamic therapy (CDT). Although ⋅OH probe-integrated CDT agents can track production by themselves, they often require complicated synthetic procedures suffer from self-consumption ⋅OH. Here, we report facile fabrication a self-monitored agent (denoted as Fc-CD-AuNCs) incorporating ferrocene (Fc) into β-cyclodextrin (CD)-functionalized gold nanoclusters (AuNCs) via host-guest molecular recognition. The water-soluble CD served not only capping to protect AuNCs but also macrocyclic host encapsulate solubilize hydrophobic Fc guest with high Fenton reactivity in vivo applications. Importantly, encapsulated inside possessed strong electron-donating ability effectively quench second near-infrared (NIR-II) fluorescence through photoinduced electron transfer. After internalization Fc-CD-AuNCs cancer cells, reaction between redox-active quencher endogenous hydrogen peroxide (H

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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Bioorthogonal In Situ Polymerization of Dendritic Agents for Hijacking Lysosomes and Enhancing Antigen Presentation in Cancer Cells

Advanced Materials, Год журнала: 2024, Номер 36(26)

Опубликована: Март 16, 2024

A low-generation lysine dendrimer, SPr-G2, responds to intracellular glutathione initiate bioorthogonal in situ polymerization, resulting the formation of large assemblies mouse breast cancer cells. The SPr-G2 can interact with lysosomes induce lysosome expansion and enhance lysosomal membrane permeabilization, leading major histocompatibility complex class I upregulation on tumor cell surfaces ultimately death. Moreover, use dendrimer conjugate chemotherapeutic drug, camptothecin (CPT), boost therapeutic potency CPT. Excellent antitumor effects vitro vivo are obtained from combinational treatment This effect also enhances immunity through promoting activation cytotoxic T cells tissues maturation dendritic study shed new light development peptide agents for therapy.

Язык: Английский

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Integration of STING activation and COX-2 inhibition via steric-hindrance effect tuned nanoreactors for cancer chemoimmunotherapy

Biomaterials, Год журнала: 2024, Номер 311, С. 122695 - 122695

Опубликована: Июнь 29, 2024

Язык: Английский

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Glutathione-Responsive and Hydrogen Sulfide Self-Generating Nanocages Based on Self-Weaving Technology To Optimize Cancer Immunotherapy

ACS Nano, Год журнала: 2024, Номер 18(14), С. 9871 - 9885

Опубликована: Март 28, 2024

As an ideal drug carrier, it should possess high loading and encapsulation efficiency precise targeting release. Herein, we utilized a template-guided self-weaving technology of phase-separated silk fibroin (SF) in reverse microemulsion (RME) to fabricate kind hyaluronic acid (HA) coated SF nanocage (HA-gNCs) for delivery cancer immunotherapy. Due the hollow structure, HA-gNCs were capable simultaneous anti-inflammatory betamethasone phosphate (BetP) immune checkpoint blockade (ICB) agent PD-L1 antibody (αPD-L1) efficiently. Another point worth noting was that thiocarbonate cross-linkers used strengthen shell could be quickly broken by overexpressed glutathione (GSH) reach responsive release inside tumor tissues accompanied hydrogen sulfide (H2S) production one step. The synergistic effect released BetP generated H2S guaranteed chronological modulation immunosuppressive microenvironment (ITME) amplify therapeutic αPD-L1 growth, metastasis, recurrence tumors. This study highlighted exceptional prospect as self-assistance platform delivery.

Язык: Английский

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An “AND” logic gate–based supramolecular therapeutic nanoplatform for combatting drug-resistant non–small cell lung cancer

Science Advances, Год журнала: 2024, Номер 10(39)

Опубликована: Сен. 25, 2024

Despite targeted therapies like epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), non–small cell lung cancer (NSCLC) remains a clinical challenge due to drug resistance hampering their efficacy. Here, we designed an “AND” logic gate–based supramolecular therapeutic platform (HA-BPY-GEF-NPs) for the treatment of EGFR-TKI resistant NSCLC. This system integrates both internal and external stimuli–responsive mechanisms that need be activated in preset sequence, enabling it precisely control release behavior enhancing precision. By programming respond sequential near-infrared (NIR) irradiation enzyme (cathepsin B) inputs, gefitinib is effectively confined tumor region. Moreover, NIR induces reactive oxygen species production, suppressing inhibiting bypass signaling pathways. The delivery offers highly controlled approach, growth, pathways, overcoming resistance, thus offering potential solution maximizing benefits.

Язык: Английский

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Evaluation of the Immunosafety of Cucurbit[n]uril In Vivo

Pharmaceutics, Год журнала: 2024, Номер 16(1), С. 127 - 127

Опубликована: Янв. 19, 2024

Cucurbiturils are a family of macrocyclic oligomers capable forming host–guest complexes with various molecules. Due to noncovalent binding drug molecules and low toxicity, cucurbiturils has been extensively investigated as potential carriers for delivery. However, the immune system’s interactions different carriers, including cucurbiturils, still under investigation. In this study, we focused on cucurbiturils’ immunosafety immunomodulation properties in vivo. We measured blood counts lymphocyte subpopulations blood, spleen, bone marrow, assessed vivo toxicity spleen marrow cells after intraperitoneal administration BALB/c mice. When assessing effect cucurbit[6]uril parameters three injections within week laboratory animals, decrease white was found mice cucurbit[6]util, but observed number normal range. At same time, cucurbit[7]uril cucurbit[8]uril did not affect leukocyte injections. Changes platelets, erythrocytes, monocytes, well several other indicators, such hematocrit or erythrocyte volumetric dispersion, were detected. show that do have immunotoxicity vivo, exception cytotoxic сucurbit[7]uril at high dosage. also evaluated cellular humoral responses. founded concentrations system action differs homologues, which is apparently associated internal environment body.

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, Год журнала: 2024, Номер 136(37)

Опубликована: Май 22, 2024

Abstract 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. 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 + /CD4 T Foxp3 depletion negligible adverse effects. This study pioneers promising avenue safe metal‐based agents immunotherapy.

Язык: Английский

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