Cancer Letters, Journal Year: 2023, Volume and Issue: 577, P. 216409 - 216409
Published: Sept. 23, 2023
Language: Английский
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
Citations
135
Science Advances, Journal Year: 2023, Volume and Issue: 9(29)
Published: July 19, 2023
The polarization of tumor-associated macrophages (TAMs) from M2 to M1 phenotype demonstrates great potential for remodeling the immunosuppressive tumor microenvironment (TME) hepatocellular carcinoma (HCC). d-lactate (DL; a gut microbiome metabolite) acts as an endogenous immunomodulatory agent that enhances Kupffer cells clearance pathogens. In this study, DL transformation TAMs was confirmed, and mechanisms underlying such were mainly due modulation phosphatidylinositol 3-kinase/protein kinase B pathway. A poly(lactide-co-glycolide) nanoparticle (NP) used load DL, DL-loaded NP modified with HCC membrane macrophage-binding peptide (M2pep), forming nanoformulation (DL@NP-M-M2pep). DL@NP-M-M2pep transformed remodeled TME in mice, promoting efficacy anti-CD47 antibody long-term animal survival. These findings reveal TAM modulatory function provide combinatorial strategy immunotherapy.
Language: Английский
Citations
110
Advanced Materials, Journal Year: 2022, Volume and Issue: 35(21)
Published: Dec. 16, 2022
Radiotherapy (RT) uses ionizing radiation to eradicate localized tumors and, in rare cases, control outside of the irradiated fields via stimulating an antitumor immune response (abscopal effect). However, therapeutic effect RT is often limited by inherent physiological barriers tumor microenvironment (TME), such as hypoxia, abnormal vasculature, dense extracellular matrix (ECM), and immunosuppressive TME. Thus, it critical develop new strategies that can remodel TME overcome radio-resistance suppression. In past decade, high-Z-element nanoparticles have been developed increase radiotherapeutic indices reducing X-ray doses side effects normal tissues enhance abscopal activating elicit systemic immunity. this review, principles radiosensitization, mechanisms suppression, use various sensitize TMEs for enhanced efficacy are discussed. The challenges clinical translation multifunctional TME-remodeling nanoradiosensitizers also highlighted.
Language: Английский
Citations
89
Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)
Published: Sept. 4, 2023
Abstract The tumor microenvironment (TME) is a highly intricate milieu, comprising multitude of components, including immune cells and stromal cells, that exert profound influence on initiation progression. Within the TME, angiogenesis predominantly orchestrated by endothelial (ECs), which foster proliferation metastasis malignant cells. interplay between with ECs complex can either bolster or hinder system. Thus, comprehensive understanding crosstalk essential to advance development immunotherapeutic interventions. Despite recent progress, underlying molecular mechanisms govern remain elusive. Nevertheless, immunomodulatory function has emerged as pivotal determinant response. In light this, study relationship checkpoints garnered considerable attention in field immunotherapy. By targeting specific pathways signaling molecules associated novel strategies may be devised enhance efficacy current treatments. this vein, we sought elucidate ECs, ultimate goal identifying therapeutic targets charting new avenues for
Language: Английский
Citations
80
Advanced Materials, Journal Year: 2022, Volume and Issue: 35(10)
Published: Dec. 28, 2022
The critical challenge for cancer vaccine-induced T-cell immunity is the sustained activation of antigen cross-presentation in antigen-presenting cells (APCs) with innate immune stimulation. In this study, it first discovered that clinically used magnetic contrast agents, iron oxide nanoparticles (IONPs), markedly augment type-I interferon (IFN-I) production profile stimulator genes (STING) agonist MSA-2 and achieve a 16-fold dosage-sparing effect human STING haplotype. Acid-ionizable copolymers are coassembled IONPs into nanoadjuvants to concentrate draining lymph nodes. top candidate nanoadjuvant (PEIM) efficiently delivers model ovalbumin (OVA) CD169+ APCs facilitates elicit 55-fold greater frequency antigen-specific CD8+ cytotoxic T-lymphocyte response than soluble antigen. PEIM@OVA nanovaccine immunization induces potent durable antitumor prevent tumor lung metastasis eliminate established tumors. Moreover, PEIM applicable deliver autologous synergizes checkpoint blockade therapy prevention postoperative recurrence distant B16-OVA melanoma MC38 colorectal models. acid-ionizable offers generalizable readily translatable strategy cascade personalized vaccination immunotherapy.
Language: Английский
Citations
75
Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(9), P. 2886 - 2910
Published: Jan. 1, 2023
Cancer vaccines have emerged as a powerful new tool for cancer immunotherapy. Adjuvants are vaccine ingredients that enhance the strength, velocity, and duration of immune response. The success adjuvants in achieving stable, safe, immunogenic has generated enthusiasm adjuvant development. Specifically, advances materials science providing insights into rational design topical Here, we outline current state engineering strategies, including those based on molecular adjuvants, polymers/lipids, inorganic nanoparticles, bio-derived materials, We also elaborate how these strategies physicochemical features involved influence effects adjuvants.
Language: Английский
Citations
59
Science Immunology, Journal Year: 2023, Volume and Issue: 8(83)
Published: May 5, 2023
The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells effective tumor control. Correlations between stimulator interferon genes (STING) pathway activation spontaneous cell in human cancers led us evaluate effect STING-activating nanoparticles (STANs), which are a polymersome-based platform for delivery cyclic dinucleotide STING agonist, on attendant effects antitumor function. In multiple mouse models, intravenous administration STANs promoted vascular normalization, evidenced by improved integrity, reduced hypoxia, increased endothelial expression adhesion molecules. STAN-mediated reprogramming enhanced infiltration, proliferation, function potentiated response immune checkpoint inhibitors adoptive therapy. We present as multimodal that activates normalizes microenvironment enhance augments responses immunotherapy.
Language: Английский
Citations
54
ACS Nano, Journal Year: 2023, Volume and Issue: 17(10), P. 9374 - 9387
Published: May 4, 2023
Stimulator of interferon genes (STING) activation by STING agonists has been recognized as one the potent and promising immunotherapy strategies. However, immunosuppressive tumor microenvironment always hinders therapeutic efficacy cancer immunotherapy. In this report, we present polymeric metal–organic framework (PMOF) nanoparticles (NPs) for combination photodynamic therapy (PDT) enhanced to improve immunotherapeutic efficacy. The PMOF NPs with poly(ethylene glycol) (PEG) shells were obtained via coordination between block copolymer ligand PEG-b-PABDA consisting 1,4-bezenedicarboxylic acid-bearing polyacrylamide (PABDA), meso-tetra(carboxyphenyl)porphyrin (TCPP), thioketal diacetic acid, zirconyl chloride. Subsequently, agonist SR-717 was loaded into porous structure obtain SR@PMOF which show excellent stability under physiological conditions. After intravenous injection accumulation, light irradiation on sites results in efficient singlet oxygen (1O2) production from TCPP cellular apoptosis release fragmented DNA tumor-associated antigens. Simultaneously, bonds can be broken 1O2 destroy rapidly SR717. PDT synergistically enhance antitumor immunity photodynamic-immunotherapy due reversal endogenous activation, suppress growth primary distant tumors efficiently. oxidation-responsive represent a delivery system simultaneous suppression metastatic rational activation.
Language: Английский
Citations
53
Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)
Published: March 13, 2024
Abstract The recent discovery of copper‐mediated and mitochondrion‐dependent cuproptosis has aroused strong interest in harnessing this novel mechanism cell death for cancer therapy. Here the design a core‐shell nanoparticle, CuP/Er, co‐delivery copper (Cu) erastin (Er) to cells synergistic ferroptosis is reported. anti‐Warburg effect Er sensitizes tumor Cu‐mediated cuproptosis, leading irreparable mitochondrial damage by depleting glutathione enhancing lipid peroxidation. CuP/Er induces immunogenic death, enhances antigen presentation, upregulates programmed death‐ligand 1 expression. Consequently, promotes proliferation infiltration T cells, when combined with immune checkpoint blockade, effectively reinvigorates mediate regression murine colon adenocarcinoma triple‐negative breast prevent metastasis. This study suggests unique opportunity synergize combination therapy nanoparticles elicit antitumor effects potentiate current immunotherapies.
Language: Английский
Citations
48
Advanced Science, Journal Year: 2023, Volume and Issue: 10(10)
Published: Feb. 5, 2023
Due to radiation resistance and the immunosuppressive microenvironment of metastatic osteosarcoma, novel radiosensitizers that can sensitize radiotherapy (RT) antitumor immunity synchronously urgently needed. Here, authors developed a nanoscale metal-organic framework (MOF, named TZM) by co-doping high-atomic elements Ta Zr as metal nodes porphyrinic molecules (tetrakis(4-carboxyphenyl)porphyrin (TCPP)) photosensitizing ligand. Given 3D arrays ultra-small heavy metals, porous TZM serves an efficient attenuator absorbing X-ray energy sensitizing hydroxyl radical generation for RT. Ta-Zr narrowed highest occupied molecular orbital-lowest unoccupied orbital (HOMO-LUMO) gap exhibited close levels between singlet triplet photoexcited states, facilitating transfer photosensitizer TCPP oxygen (
Language: Английский
Citations
47