NIR‐Activatable Heterostructured Nanoadjuvant CoP/NiCoP Executing Lactate Metabolism Interventions for Boosted Photocatalytic Hydrogen Therapy and Photoimmunotherapy

Advanced Materials, Год журнала: 2023, Номер 36(5)

Опубликована: Ноя. 2, 2023

Near-infrared (NIR) laser-induced photoimmunotherapy has aroused great interest due to its intrinsic noninvasiveness and spatiotemporal precision, while immune evasion evoked by lactic acid (LA) accumulation severely limits clinical outcomes. Although several metabolic interventions have been devoted ameliorate immunosuppression, intracellular residual LA still remains a potential energy source for oncocyte proliferation. Herein, an immunomodulatory nanoadjuvant based on yolk-shell CoP/NiCoP (CNCP) heterostructure loaded with the monocarboxylate transporter 4 inhibitor fluvastatin sodium (Flu) is constructed concurrently relieve immunosuppression elicit robust antitumor immunity. Under NIR irradiation, CNCP heterojunctions exhibit superior photothermal performance photocatalytic production of reactive oxygen species hydrogen. The continuous heat then facilitates Flu release restrain exudation from tumor cells, whereas cumulative can be depleted as hole scavenger improve efficiency. Subsequently, potentiated therapy not only initiate systematic immunoreaction, but also provoke severe mitochondrial dysfunction disrupt supply shock protein synthesis, in turn realizing mild therapy. Consequently, remodeling endows intensive cascade treatment optimal safety profile effectually suppress proliferation metastasis, which offers new paradigm development metabolism-regulated immunotherapy.

Язык: Английский

---

Current Advances on Nanomaterials Interfering with Lactate Metabolism for Tumor Therapy

Advanced Science, Год журнала: 2023, Номер 11(3)

Опубликована: Ноя. 8, 2023

Abstract Increasing numbers of studies have shown that tumor cells prefer fermentative glycolysis over oxidative phosphorylation to provide a vast amount energy for fast proliferation even under oxygen‐sufficient conditions. This metabolic alteration not only favors cell progression and metastasis but also increases lactate accumulation in solid tumors. In addition serving as byproduct glycolytic cells, plays central role the construction acidic immunosuppressive microenvironment, resulting therapeutic tolerance. Recently, targeted drug delivery inherent properties nanomaterials attracted great attention, research on modulating metabolism based enhance antitumor therapy has exploded. this review, advanced strategies interfere with are discussed, including inhibiting anabolism, promoting catabolism, disrupting “lactate shuttle”. Furthermore, recent advances combining modulation other therapies, chemotherapy, immunotherapy, photothermal therapy, reactive oxygen species‐related etc., which achieved cooperatively enhanced outcomes, summarized. Finally, foreseeable challenges prospective developments reviewed future development field.

Язык: Английский

---

Lactate Efflux Inhibition by Syrosingopine/LOD Co‐Loaded Nanozyme for Synergetic Self‐Replenishing Catalytic Cancer Therapy and Immune Microenvironment Remodeling

Advanced Science, Год журнала: 2023, Номер 10(26)

Опубликована: Июнь 29, 2023

An effective systemic mechanism regulates tumor development and progression; thus, a rational design in one-stone-two-birds strategy is meant for cancer treatment. Herein, hollow Fe

Язык: Английский

---

Boosting Energy Deprivation by Synchronous Interventions of Glycolysis and Oxidative Phosphorylation for Bioenergetic Therapy Synergetic with Chemodynamic/Photothermal Therapy

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Март 15, 2024

Abstract Bioenergetic therapy is emerging as a promising therapeutic approach. However, its effectiveness restricted by metabolic plasticity, tumor cells switch phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) to compensate for energy. Herein, Metformin (MET) BAY‐876 (BAY) co‐loaded CuFe 2 O 4 (CF) nanoplatform (CFMB) developed boost energy deprivation synchronous interventions of OXPHOS bioenergetic synergetic with chemodynamic/photothermal (CDT/PTT). The MET can simultaneously restrain inhibiting hexokinase (HK2) activity damaging mitochondrial function deprive energy, respectively. Besides, BAY blocks glucose uptake transporter 1 (GLUT1) expression, further potentiating the repression thus achieving much more depletion tumorigenic sources. Interestingly, upregulated antioxidant glutathione (GSH) in cancer triggers CFMB degradation release Cu + /Fe 2+ catalyzing tumor‐overexpressed H hydroxyl radical (∙OH), both impairing GSH‐depletion amplified CDT. Furthermore, upon near‐infrared (NIR) light irradiation, has photothermal conversion capacity kill PTT improve ∙OH production enhanced In vivo experiments have manifested that remarkably suppressed growth mice without systemic toxicity. This study provides new modality paradigm bioenergetic‐related therapies.

Язык: Английский

---

Nanozyme-enhanced ferroptosis for cancer treatment

Materials Chemistry Frontiers, Год журнала: 2024, Номер 8(7), С. 1685 - 1702

Опубликована: Янв. 1, 2024

Nanozymes could mimic the catalytic activity of natural enzymes, then stimulate Fenton reaction for reactive oxygen species overproduction and lipid peroxidation, ultimately induce ferroptosis to exert anticancer effects.

Язык: Английский

---

A Novel Nanozyme to Enhance Radiotherapy Effects by Lactic Acid Scavenging, ROS Generation, and Hypoxia Mitigation

Advanced Science, Год журнала: 2024, Номер 11(26)

Опубликована: Май 5, 2024

Abstract Uveal melanoma (UM) is a leading intraocular malignancy with high 5‐year mortality rate, and radiotherapy the primary approach for UM treatment. However, elevated lactic acid, deficiency in ROS, hypoxic tumor microenvironment have severely reduced outcomes. Hence, this study devised novel CoMnFe‐layered double oxides (LDO) nanosheet multienzyme activities enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H 2 O ) into oxygen reactive species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, efficiently scavenged thereby impeding DNA protein repair cells to synergistically enhance effect of Moreover, density functional theory (DFT) calculations decoded transformation pathway from pyruvic elucidating previously unexplored facet activity. The introduction innovative nanomaterial paves way novel, targeted, highly effective therapeutic approach, offering new avenues management other cancer types.

Язык: Английский

---

Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI

Metabolites, Год журнала: 2025, Номер 15(3), С. 201 - 201

Опубликована: Март 13, 2025

Background: Tumor cells engage in continuous self-replication by utilizing a large number of resources and capabilities, typically within an aberrant metabolic regulatory network to meet their own demands. This dysregulation leads the formation tumor microenvironment (TME) most solid tumors. Nanomedicines, due unique physicochemical properties, can achieve passive targeting certain tumors through enhanced permeability retention (EPR) effect, or active deliberate design optimization, resulting accumulation TME. The use nanomedicines target critical pathways holds significant promise. However, requires careful selection relevant drugs materials, taking into account multiple factors. traditional trial-and-error process is relatively inefficient. Artificial intelligence (AI) integrate big data evaluate delivery efficiency nanomedicines, thereby assisting nanodrugs. Methods: We have conducted detailed review key papers from databases, such as ScienceDirect, Scopus, Wiley, Web Science, PubMed, focusing on reprogramming, mechanisms action development metabolism, application AI empowering nanomedicines. integrated content present current status research metabolism potential future directions this field. Results: Nanomedicines possess excellent TME which be utilized disrupt cells, including glycolysis, lipid amino acid nucleotide metabolism. disruption selective killing disturbance Extensive has demonstrated that AI-driven methodologies revolutionized nanomedicine development, while concurrently enabling precise identification molecular regulators involved oncogenic reprogramming pathways, catalyzing transformative innovations targeted cancer therapeutics. Conclusions: great Additionally, will accelerate discovery metabolism-related targets, empower optimization help minimize toxicity, providing new paradigm for development.

Язык: Английский

---

Strategic disruption of cancer’s powerhouse: precise nanomedicine targeting of mitochondrial metabolism

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 8, 2024

Abstract Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as hub oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels variety cellular activities. Disruption mitochondrial is common feature many diseases, including cancer, neurodegenerative conditions cardiovascular diseases. Targeting tumor cell with multifunctional nanosystems emerges promising strategy for enhancing therapeutic efficacy against cancer. review comprehensively outlines pathways metabolism, emphasizing their critical roles energy production metabolic regulation. The associations between aberrant initiation progression cancer highlighted, illustrating how these disruptions contribute oncogenesis sustainability. More importantly, innovative strategies employing nanomedicines precisely target therapy fully explored. Furthermore, key challenges future directions this field identified discussed. Collectively, provides comprehensive understanding current state potential nanomedicine targeting offering insights developing more effective therapies.

Язык: Английский

---

Nanozyme-based cancer theranostics: A scientometric analysis and comprehensive review

Nano Today, Год журнала: 2024, Номер 57, С. 102386 - 102386

Опубликована: Июль 13, 2024

Язык: Английский

---

Boosting Ferroptosis and immunotherapy for Colorectal Cancer by Lactate‐Related Metabolic Reprogramming

Advanced Functional Materials, Год журнала: 2024, Номер 34(52)

Опубликована: Авг. 27, 2024

Abstract As the presence of anaerobic metabolism glucose, solid tumors characteristically display higher levels lactate production, which attenuate ferroptosis therapy and subsequent anti‐tumor immune response. Herein, hyaluronic acid (HA)‐modified oxidase (LOX)‐loaded nanoscale metal organic frameworks (MOFs), termed as FCS@LOX@HA (FCSLH) is constructed, achieving tumor‐targeted metabolic combined chemo‐dynamic (CDT). Notably, high LOX‐loading capacity MOFs achieved by adjusting Fe/Cu ratio. Upon internalization cancer cells, FCS reacted with local glutathione (GSH) to release ions for CDT. Meanwhile, LOX catalyzed endogenous pyruvate accompanied a H 2 O ; while latter can enhance MOFs‐mediated CDT effect. Additionally, exhaustion impair antioxidant system inhibiting HIF‐1α/SLC1A1 pathway, resulting in accumulation lipid peroxidation, occurs immunogenic cell death. Furthermore, within tumor‐associated macrophages (TAMs) inhibit M2 macrophage polarization suppressing NF‐κB/HIF‐1α thereby augmenting The vivo studies demonstrated that cooperating PD‐L1 antibodies achieve excellent therapeutic efficacy. Taken together, FCSLH amplify ferroptosis‐mediated response through simultaneous dysfunction cells TAMs, provides novel insight integrating programmed immunotherapy.

Язык: Английский

---