Carrier-free nanoparticles for cancer theranostics with dual-mode magnetic resonance imaging/fluorescence imaging and combination photothermal and chemodynamic therapy

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125285 - 125285

Published: Jan. 1, 2025

Language: Английский

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Biometallic ions and derivatives: a new direction for cancer immunotherapy

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 15, 2025

Biometallic ions play a crucial role in regulating the immune system. In recent years, cancer immunotherapy has become breakthrough treatment, achieving good efficacy wide range of cancers with its specificity and durability advantages. However, existing therapies still face challenges, such as tolerance escape. (e.g. zinc, copper, magnesium, manganese, etc.) can assist enhancing through activation cells, enhancement tumor antigen presentation, improvement microenvironment. addition, biometallic derivatives directly inhibit cell progression offer possibility effectively overcoming limitations current by promoting responses reducing immunosuppressive signals. This review explores potential application prospects immunotherapy, providing new ideas for future clinical metal part helping to guide development more effective safe therapeutic regimens.

Language: Английский

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Immunomodulatory metal-based biomaterials for cancer immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 375, P. 249 - 268

Published: Sept. 12, 2024

Language: Английский

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Robust and Sustained STING Pathway Activation via Hydrogel-Based In Situ Vaccination for Cancer Immunotherapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(43), P. 29439 - 29456

Published: Oct. 15, 2024

The stimulator of interferon genes (STING) pathway is crucial for tumor immunity, leading to the exploration STING agonists as potential immunotherapy adjuvants. However, their clinical application faces obstacles including poor pharmacokinetics, transient activation, and an immunosuppressive microenvironment (TME). Addressing these limitations, our study aims develop injectable silk fibroin hydrogel-based in situ vaccine. It incorporates a nanoscale agonist, immunogenic cell death (ICD) inducer, immunomodulator ensure controlled sustained release. cGAMP nanoparticles (cGAMPnps) with core–shell structure optimal delivery dendritic cells (DCs), thereby activating fostering DC maturation. ICD-associated damage-associated molecular patterns amplify prolong activation via enhanced type I IFN other inflammatory pathways, along delayed degradation STING. Furthermore, STING-driven vascular normalization by cGAMPnps ICD, conjunction immunomodulators like antiprogrammed protein 1 antibody (anti-PD-1 Ab) or OX40 ligand (OX40L), effectively remodels TME. This gel vaccine, when used independently surgery neoadjuvant/adjuvant immunotherapy, enhances CD8+ T-cell suppressing progression recurrence across various immunologically cold models. revolutionizes cancer offering substantial promise improving outcomes broad spectrum malignancies.

Language: Английский

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Facile integration of a binary nano-prodrug with αPD-L1 as a translatable technology for potent immunotherapy of TNBC

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Modified probiotics and the related combinatorial therapeutics

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Dual-modality immune nano-activator harnessing Mn2⁺ and quercetin to potentiate the cGAS-STING pathway for advanced cancer metalloimmunotherapy

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 25, 2025

Manganese ions (Mn2+) have emerged as promising activators of the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway. However, their clinical application was hindered by low bioavailability and limited immune activation pathways, which impaired ability to trigger robust responses achieve significant antitumor effects. To address these challenges, we developed a dual-modality nano-activator coordinating manganese with quercetin. This strategy designed enhance cGAS-STING pathway elicit immunogenic cell death, thereby strengthening response. The engineered demonstrated superior tumor-targeting efficient cellular internalization. Upon exposure near-infrared irradiation, system harnessed photothermal effects induce apoptosis in tumor cells while simultaneously accelerating release released facilitated generation reactive oxygen species, conjunction quercetin-induced apoptosis, amplified photothermal-induced DNA damage. damage further promoted cytosolic DNA, turn activated pathway, intensifying activation. Notably, also triggered synergized promote dendritic maturation activate antigen-specific T-cell, significantly enhancing response against tumor. Both vitro vivo studies confirmed that this effectively inhibited growth, particularly pronounced when combined anti-CTLA-4 antibodies.

Language: Английский

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Manganese-Doped Nanoparticles with Hypoxia-Inducible Factor 2α Inhibitor That Elicit Innate Immune Responses against von Hippel–Lindau Protein-Deficient Tumors

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

The von Hippel-Lindau (VHL) tumor suppressor gene product, pVHL, is frequently deficient in a variety of human cancers. In addressing the treatment pVHL-deficient tumors, hypoxia-inducible factor 2α (HIF-2α) has risen as promising therapeutic target, culminating development specific inhibitors like PT2385 and its analogues. Nonetheless, absence targeted delivery capabilities these heightens risk on-target toxicities. To mitigate limitations, we have engineered nanoparticle, termed PMMF (PT/MMSN@DSPE-PEG-FA), capable delivering both HIF-2α antagonist (PT2385) manganese directly to sites. shown effective targeting clear-cell renal cell carcinoma melanoma, leading significant benefits alleviating hypoxic immunosuppressive traits microenvironment. Functionally, boosts cyclic GMP-AMP synthase-stimulator interferon genes signaling pathway, which, turn, stimulates robust innate immune response. This response activates natural killer (NK) cells CD8+ T lymphocytes while curbing infiltration regulatory cells. Notably, efficacy markedly reduced when NK are blocked but not affected by neutrophil blockade, highlighting critical role PMMF-induced antitumor immunity. Additionally, safety profile showed minimal systemic post-treatment cytotoxicity. summary, our findings position platform for treating tumors with pVHL deficiency underscore potential metalloimmunotherapy.

Language: Английский

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Manganese-Based Nanotherapeutics for Targeted Treatment of Breast Cancer

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Breast cancer (BC) is one of the most common cancers among women and associated with high mortality. Traditional modalities, including surgery, radiotherapy, chemotherapy, have achieved certain advancements but continue to combat challenges harm healthy tissues, resistance treatment, adverse drug reactions. The rapid in nanotechnology recently facilitated exploration innovative strategies for breast therapy. Manganese-based nanotherapeutics attracted great attention because their unique characteristics such as tunable structures/morphologies, versatility, magnetic/optical properties, strong catalytic activities, excellent biodegradability, biocompatibility. In this review, we highlighted different types Mn-based modulate TME, metal-immunotherapy, alleviating tumor hypoxia, increasing reactive oxygen species production, emphasized its role magnetic resonance imaging (MRI)-guided therapy, photoacoustic imaging, theranostic-based therapy along a therapeutic carrier, all which were discussed context cancer. Hopefully, present review will provide insights into current landscape future directions multifunctional applications field treatment.

Language: Английский

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Discovery of Airway-Administered Ionophores for Mn²⁺ to Mitigate Lung Metastasis by Targeting Disseminated Tumor Cell

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Activation of the STING pathway is essential for restoring immune surveillance against dormant disseminated tumor cells (DTCs) in lungs. Inhaled Mn2+ has potential as a agonist; however, its clinical application limited by risk chronic inflammation and metastasis, primarily due to reactive oxygen species (ROS) generation during inhalation. To address these risks, salvianolic acid B (salB) was identified an effective ionophore Mn2+, enhancing activation while mitigating ROS-induced inflammation. In this study, salB mitigated Mn2+-induced ROS levels enhanced signaling, providing safer, noninflammatory approach activating lung DTCs. The salB-Mn2+ complexes were encapsulated human serum albumin nanoparticles (HSA NPs) PET MRI analyses revealed that intratracheal administration HSA NP@salB-Mn2+ restricted Mn2+'s systemic distribution, retaining it lungs minimizing central nervous system accumulation. Subsequent immunofluorescence further confirmed effectively targeted metastatic lesions. Despite extended retention tissue, histological analysis showed minimal mice treated with NP@salB-Mn2+, contrast those receiving MnCl2 or MnO. Consequently, demonstrated superior suppression 4T1 cell metastasis postsurgical relative Mechanistically, functions agonist, independently p-STING, which synergizes significantly amplify signaling downstream target engagement. mouse model, combination αPD-1 antibody reduced DTC dormancy detection, confirming immunotherapeutic potential. These findings establish promising inhalable treatment, three key advantages: prolonged retention, risk, STING-activating efficacy.

Language: Английский

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