Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 2, 2024

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, immune cells, plays a crucial role response modulation. Nanoparticles, engineered to reshape TME, shown promising results enhancing by facilitating targeted These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, encourage T infiltration. Biomimetic further enhance increasing internalization agents cells such as cells. Moreover, exosomes, whether naturally secreted body or bioengineered, been explored regulate TME immune-related affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated pH, redox, light conditions, exhibit potential accelerate co-application with checkpoint inhibitors is an emerging strategy boost anti-tumor immunity. With their ability induce long-term immunity, nanoarchitectures are structures development. This review underscores critical overcoming current driving advancement modification.

Language: Английский

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Impairing Tumor Metabolic Plasticity via a Stable Metal‐Phenolic‐Based Polymeric Nanomedicine to Suppress Colorectal Cancer

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(23)

Published: March 14, 2023

Targeting metabolic vulnerability of tumor cells is a promising anticancer strategy. However, the therapeutic efficacy existing metabolism-regulating agents often compromised due to tolerance resulting from plasticity, as well their poor bioavailability and tumor-targetability. Inspired by inhibitive effect N-ethylmaleimide on mitochondrial function, dendronized-polymer-functionalized metal-phenolic nanomedicine (pOEG-b-D-SH@NP) encapsulating maleimide-modified doxorubicin (Mal-DOX) developed enable improvement in overall delivery efficiency inhibition metabolism via multiple pathways. It observed that Mal-DOX its derived induces energy depletion CT26 colorectal cancer more efficiently than doxorubicin, shifts balance programmed cell death apoptosis toward necroptosis. Notably, pOEG-b-D-SH@NP simultaneously inhibits cellular oxidative phosphorylation glycolysis, thus potently suppressing growth peritoneal intestinal metastasis mouse models. Overall, study provides dendronized-polymer-derived nanoplatform for treatment cancers through impairing plasticity.

Language: Английский

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An Activatable Phototheranostic Probe for Anti‐hypoxic Type I Photodynamic‐ and Immuno‐Therapy of Cancer

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(4)

Published: Aug. 29, 2023

Photodynamic therapy (PDT), which utilizes type I photoreactions, has great potential as an effective cancer treatment because of its hypoxia-tolerant superiority over the commonly used II pathway. A few photosensitizers are exploited; however, they majorly induce cytotoxicity and possess poor tumor specificity low-efficient theranostics. To resolve this issue, herein aminopeptidase N (APN)-activated phototheranostic probe (CyA) is reported for anti-hypoxic PDT in conjunction with immunotherapy treatment. CyA can specifically activate near-infrared fluorescence, photoacoustic signals, phototoxicity following APN-induced substrate cleavage subsequent generation active molecules (such CyBr). endows specific imaging capabilities toward cells overexpressing APN under both normoxia hypoxia. In addition, locally activatable induces systemic antitumor immune responses. More importantly, integration localized activated evokes enhanced therapeutic effects improved inhibition efficiency live mice compared individual treatments. This study aims to present combination therapy.

Language: Английский

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Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(10), P. 9126 - 9139

Published: April 25, 2023

Administration of bispecific antibodies (biAbs) in tumor therapy is limited by their short half-life and off-target toxicity. Optimized strategies or targets are needed to overcome these barriers. B7-H3 (CD276), a member the B7 superfamily, associated with poor survival glioblastoma (GBM) patients. Moreover, dimer EGCG (dEGCG) synthesized this work enhanced IFN-γ-induced ferroptosis cells vitro vivo. Herein, we prepared recombinant anti-B7-H3×CD3 biAbs constructed MMP-2-sensitive S-biAb/dEGCG@NPs offer combination treatment strategy for efficient systemic GBM elimination. Given targeted delivery microenvironment responsiveness, displayed intracranial accumulation, 4.1-, 9.5-, 12.3-fold higher than that biAb/dEGCG@NPs, biAb/dEGCG complexes, free biAbs, respectively. Furthermore, 50% GBM-bearing mice S-biAb/dEGCG@NP group survived longer 56 days. Overall, can induce elimination boosting effect enhancing immune checkpoint blockade (ICB) immunotherapy may be successful antibody nanocarriers cancer therapy.

Language: Английский

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Self-Assembled Nano-PROTAC Enables Near-Infrared Photodynamic Proteolysis for Cancer Therapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16642 - 16649

Published: July 21, 2023

Confining the protein degradation activity of proteolysis-targeting chimera (PROTAC) to cancer lesions ensures precision treatment. However, it still remains challenging precisely control PROTAC function in tumor regions vivo. We herein describe a near-infrared (NIR) photoactivatable nano-PROTAC (NAP) for remote-controllable proteolysis tumor-bearing mice. NAP is formed by molecular self-assembly from an amphiphilic conjugate linked with NIR photosensitizer through singlet oxygen (1O2)-cleavable linker. The initially silenced but can be remotely switched on upon photoirradiation generate 1O2 photosensitizer. demonstrated that enabled tumor-specific bromodomain-containing 4 (BRD4) light-instructed manner. This combination photodynamic therapy (PDT) elicited effective suppression growth. work thus presents novel approach spatiotemporal over targeted PROTAC.

Language: Английский

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New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 21, 2024

Abstract Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit endogenous E3 ubiquitin ligases facilitate degradation of interest (POIs) through ubiquitin–proteasome system (UPS) in cyclic catalytic manner. Despite recent endeavors advance utilization clinical settings, majority fail progress beyond preclinical phase drug development. There are multiple factors impeding market entry PROTACs, insufficiently precise favorable POIs standing out as one most formidable obstacles. Recently, there been exploration new-generation advanced including PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, improve vivo efficacy PROTACs. These improved possess capability mitigate undesirable physicochemical characteristics inherent thereby enhancing their targetability reducing off-target side effects. The will mark pivotal turning point realm targeted protein degradation. In this comprehensive review, we meticulously summarized state-of-the-art advancements achieved by these cutting-edge elucidated underlying design principles, deliberated upon prevailing encountered, provided an insightful outlook on future prospects within field.

Language: Английский

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Targeted protein degradation: advances in drug discovery and clinical practice

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 6, 2024

Abstract Targeted protein degradation (TPD) represents a revolutionary therapeutic strategy in disease management, providing stark contrast to traditional approaches like small molecule inhibitors that primarily focus on inhibiting function. This advanced technology capitalizes the cell’s intrinsic proteolytic systems, including proteasome and lysosomal pathways, selectively eliminate disease-causing proteins. TPD not only enhances efficacy of treatments but also expands scope applications. Despite its considerable potential, faces challenges related properties drugs their rational design. review thoroughly explores mechanisms clinical advancements TPD, from initial conceptualization practical implementation, with particular proteolysis-targeting chimeras molecular glues. In addition, delves into emerging technologies methodologies aimed at addressing these enhancing efficacy. We discuss significant trials highlight promising outcomes associated drugs, illustrating potential transform treatment landscape. Furthermore, considers benefits combining other therapies enhance overall effectiveness overcome drug resistance. The future directions applications are explored, presenting an optimistic perspective further innovations. By offering comprehensive overview current innovations faced, this assesses transformative revolutionizing development setting stage for new era medical therapy.

Language: Английский

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Nano-PROTACs: state of the art and perspectives

Nanoscale, Journal Year: 2024, Volume and Issue: 16(9), P. 4378 - 4391

Published: Jan. 1, 2024

Schematic illustration of the combinational strategy nanotechnology and PROTACs (Nano-PROTACs): typical shortcomings traditional nanotechnology-based strategies for PROTAC drugs optimization.

Language: Английский

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Magnetic-Manipulated NK Cell Proliferation and Activation Enhance Immunotherapy of Orthotopic Liver Cancer

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(24), P. 13147 - 13160

Published: June 1, 2023

The immunotherapy of deep solid tumors in the human body, such as liver cancer, still faces great challenges, especially inactivation and insufficient infiltration immune cells tumor microenvironment. Natural killer (NK) are gaining ever-increasing attention owing to their unique features expected play an important role cancer immunotherapy. However, NK severely inactivated due highly immunosuppressive intratumor microenvironment, resulting poor clinical therapeutic efficacy. Herein, we propose a mild magnetocaloric regulation approach using magnetogenetic nanoplatform MNPs@PEI-FA/pDNA (MPFD), which is synthesized by loading heat-inducible plasmid DNA (HSP70-IL-2-EGFP) on polyethyleneimine (PEI)- folic acid (FA)-modified ZnCoFe2O4@ZnMnFe2O4 magnetic nanoparticles (MNPs) promote proliferation activation tumor-infiltrating under manipulation without limitation penetration depth for orthotopic magnetothermally responsive MPFD serves magnetism-heat nanotransducer induce gene transcription IL-2 cytokine cell activation. Both vitro vivo results demonstrate that remote (∼40 °C) initiates HSP70 promoter trigger overexpression subsequent secretion, leading situ expansion through IL-2/IL-2 receptor (IL-2R) pathways prominent inhibition. This work not only evidences potential but also reveals underlying mechanism treatment nanoplatform.

Language: Английский

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A comprehensive review on peptide-bearing biomaterials: From ex situ to in situ self-assembly

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 502, P. 215600 - 215600

Published: Dec. 14, 2023

Language: Английский

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