Metformin-based nanomedicines for reprogramming tumor immune microenvironment

Theranostics, Год журнала: 2024, Номер 15(3), С. 993 - 1016

Опубликована: Дек. 2, 2024

Immunotherapy has transformed current cancer management, and it achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing activity immune cells facilitating immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator cellular energy metabolism homeostasis, gained growing attention in anti-tumor immunity. Metformin is usually considered as cornerstone diabetes its role activating AMPK pathway also been extensively explored therapy although findings on remain inconsistent. nanomedicine formulation found to hold potential reprogramming TME through immunometabolic modulation both cells. This review elaborates foundation via metformin-based nanomedicines, offering valuable insights for next generation therapy.

Язык: Английский

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Dendritic Polymer‐Based Nanomedicines Remodel the Tumor Stroma: Improve Drug Penetration and Enhance Antitumor Immune Response

Advanced Materials, Год журнала: 2024, Номер 36(25)

Опубликована: Март 12, 2024

Abstract The dense extracellular matrix (ECM) in solid tumors, contributed by cancer‐associated fibroblasts (CAFs), hinders penetration of drugs and diminishes their therapeutic outcomes. A sequential treatment strategy remodeling the ECM via a CAF modifier (dasatinib, DAS) is proposed to promote an immunogenic cell death (ICD) inducer (epirubicin, Epi) apoptotic vesicles, ultimately enhancing efficacy against breast cancer. Dendritic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)‐based nanomedicines (poly[OEGMA‐Dendron(G2)‐Gly‐Phe‐Leu‐Gly‐DAS] (P‐DAS) poly[OEGMA‐Dendron(G2)‐hydrazone‐Epi] (P‐Epi)) are developed for delivery DAS Epi, respectively. P‐DAS reprograms CAFs reduce collagen downregulating anabolism energy metabolism, thereby reducing deposition. regulated can enhance tumor P‐Epi strengthen its ICD effect, leading amplified antitumor immune response. In cancer‐bearing mice, this approach alleviates barrier, resulting reduced burden increased cytotoxic T lymphocyte infiltration, more encouragingly, synergizes effectively with anti‐programmed 1 (PD‐1) therapy, significantly inhibiting growth preventing lung metastasis. Furthermore, systemic toxicity barely detectable after P‐Epi. This opens new avenue treating desmoplastic tumors metabolically targeting overcome barrier.

Язык: Английский

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Dendritic nanomedicine enhances chemo-immunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(8), С. 3680 - 3696

Опубликована: Март 9, 2024

Inefficient drug penetration hurdled by the stroma in tumor tissue leads to a diminished therapeutic effect for drugs and reduced infiltration level of immune cells. Herein, we constructed PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) regulate metabolism cancer-associated fibroblasts (CAFs), thus enhancing Epi into both multicellular spheroids (MTSs) tissues mouse colon cancer (CT26), breast (4T1) human (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs remarkable antitumor efficacy Epi-P4D were ascribed fibronectin, α-SMA, collagen secretion. Besides, thinning efficient eradication cells promoted immunogenic cell death (DC) maturation subsequent activation, including elevating CD4+ T population, reducing CD8+ hyperactivation exhaustion, amplifying natural killer (NK) proportion effectively activating them. As result, this nanomedicine thinned enhance facilitate elevated efficacy.

Язык: Английский

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Co-activating STING-TLR9 pathways promotes radiotherapy-induced cancer vaccination

Journal of Controlled Release, Год журнала: 2025, Номер 379, С. 327 - 343

Опубликована: Янв. 14, 2025

Язык: Английский

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PD-L1 siRNA incorporation into a cationic liposomal tumor mRNA vaccine enhances cytotoxic T cell activation and prevents immune evasion

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101603 - 101603

Опубликована: Фев. 22, 2025

Язык: Английский

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Transformative effects of homo-valence ion doping on persistent luminescence nanophosphors for radiotherapy monitoring

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 161412 - 161412

Опубликована: Март 1, 2025

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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Amino Acid Metabolism-Regulated Nanomedicine for Enhanced Tumor Immunotherapy through Synergistic Regulation of Immune Microenvironment

Biomaterials Research, Год журнала: 2024, Номер 28

Опубликована: Янв. 1, 2024

The reprogramming of tumor metabolism presents a substantial challenge for effective immunotherapy, playing crucial role in developing an immunosuppressive microenvironment. In particular, the degradation amino acid L-tryptophan (Trp) to kynurenine (Kyn) by indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) is one most clinically validated pathways immune suppression. Thus, regulating Trp/Kyn IDO1 inhibition represents promising strategy enhancing immunotherapy. Herein, metabolism-regulated nanoparticles are prepared through metal coordination-driven assembly inhibitor (NLG919) and stimulator interferon genes (STING) agonist (MSA-2) enhanced After intravenous administration, assembled could efficiently accumulate tumors, bioavailability NLG919 down-regulating Trp Kyn remodel Meanwhile, released MSA-2 evoked potent STING pathway activation triggering response. antitumor immunity induced significantly inhibited development primary metastatic as well B16 melanoma. Overall, this study provided novel paradigm immunotherapy synergistic activation.

Язык: Английский

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Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(22), С. 28104 - 28117

Опубликована: Май 20, 2024

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, clinical translational application SDT impeded by lack efficient sonosensitizers, inefficient accumulation at tumor sites, and complicated immunosuppressive microenvironment. Herein, we developed facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared incorporating chemotherapeutic mitoxantrone into one-step synthesis process disulfide bond containing polymers, followed loading with sonosensitizer (HMME) camouflaging cell membrane. Due membrane camouflage, this showed prolonged blood circulation targeting aggregation. Under exhibited satisfactory performance both in vitro vivo. Moreover, potent combined glutathione-responsive drug release cells induced robust immunogenic death enhance antitumor effect turn. Overall, shows great potential

Язык: Английский

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Hypoxia-Specific Metal–Organic Frameworks Augment Cancer Immunotherapy of High-Intensity Focused Ultrasound

ACS Nano, Год журнала: 2024, Номер 18(28), С. 18412 - 18424

Опубликована: Июль 1, 2024

As a noninvasive treatment modality, high-intensity focused ultrasound (HIFU)-induced antitumor immune responses play vital role in surgery prognosis. However, limited response intensity largely hinders postoperative immunotherapy. Herein, hypoxia-specific metal-organic framework (MOF) nanosystem, coordinated by Fe3+, hypoxic-activated prodrug AQ4N, and IDO-1 signaling pathway inhibitor NLG919, is developed for the potentiating immunotherapy of HIFU surgery. The loaded AQ4N enhances photoacoustic imaging effects to achieve accurate intraoperative navigation. Within HIFU-established severe hypoxic environment, activated sequentially, following which it cooperates with Fe3+ effectively provoke immunogenic cell death. In addition, potent NLG919 suppresses activity degrades immunosuppressive tumor microenvironment aggravated hypoxia. vivo studies demonstrate that MOF-mediated greatly inhibits growth primary/distant tumors eliminates lung metastasis. This work establishes robust delivery platform improve overall prognosis high specificity potency.

Язык: Английский

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