Metal–organic framework-based smart stimuli-responsive drug delivery systems for cancer therapy: advances, challenges, and future perspectives

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

Published: Feb. 28, 2025

Cancer treatment is currently one of the most critical healthcare issues globally. A well-designed drug delivery system can precisely target tumor tissues, improve efficacy, and reduce damage to normal tissues. Stimuli-responsive systems (SRDDSs) have shown promising application prospects. Intelligent nano responsive endogenous stimuli such as weak acidity, complex redox characteristics, hypoxia, active energy metabolism, well exogenous like high temperature, light, pressure, magnetic fields are increasingly being applied in chemotherapy, radiotherapy, photothermal therapy, photodynamic various other anticancer approaches. Metal–organic frameworks (MOFs) become candidate materials for constructing SRDDSs due their large surface area, tunable porosity structure, ease synthesis modification, good biocompatibility. This paper reviews MOF-based modes cancer therapy. It summarizes key aspects, including classification, synthesis, modifications, loading modes, stimuli-responsive mechanisms, roles different modalities. Furthermore, we address current challenges summarize potential applications artificial intelligence MOF synthesis. Finally, propose strategies enhance efficacy safety SRDDSs, ultimately aiming at facilitating clinical translation.

Language: Английский

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Epigenetic drugs in cancer therapy

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 26, 2025

Abstract Genetic and epigenetic modifications of DNA are involved in cancer initiation progression. Epigenetic change chromatin structure accessibility thus affect replication, repair transcription. reversible include methylation, histone acetylation methylation. methylation is catalysed by methyltransferases, deacetylation acetylases deacetylases, while methyltransferases. dysregulated several cancers, making them therapeutic targets. drugs (epi-drugs) which inhibitors methyltransferase (DNMTi), deacetylase (HDACi), (HMTi) bromodomain extra-terminal motif protein (BETi), have demonstrated clinical success as anti-cancer agents. Furthermore, the combination epi-drugs with standard chemotherapeutic agents has promising effects pre-clinical settings. In this review, we discuss role therapy explore their current future use other used clinic. We further highlight side limitations epi-drugs. additionally novel delivery methods tumour biomarkers for screening, diagnosis development personalised treatments, order to reduce off-target toxicity improve specificity anti-tumour efficacy

Language: Английский

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Anticancer properties of histone deacetylase inhibitors – what is their potential?

Expert Review of Anticancer Therapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Jan. 10, 2025

Introduction Histone modifications are crucial epigenetic mechanisms for regulating gene expression. acetyltransferases and deacetylases (HDACs) catalyze histone acetylation, a process that mediates transcription. Over recent decades, studies have demonstrated targeting acetylation can be effective in cancer treatment, leading to the development approval of several HDAC inhibitors.

Language: Английский

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CD47 blockade reverses resistance to HDAC inhibitor by liberating anti-tumor capacity of macrophages

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 24, 2025

Abstract Background Targeting oncogenic histone modification by deacetylase inhibitors (HDACis) demonstrates promising prospects in clinical cancer treatment, whereas a notable proportion of patients cannot benefit from HDACi therapy. This study aims to explore how influences the tumor microenvironment, order identify potential targets for reversing resistance therapies. Methods Macrophage infiltration was compared between HDACi-responding and HDACi-nonresponding patients. The impact HDACis on phagocytic capacity macrophages investigated through macrophage-tumor cell co-culture system. CD47 expression lines patient-derived organoids evaluated quantitative polymerase chain reaction (QPCR) flow cytometry. Mechanistic studies were conducted co-immunoprecipitation (co-IP) chromatin immunoprecipitation (ChIP). synergistic effect neutralizing antibody assessed subcutaneous murine models. Bioinformatics approaches adopted analyze macrophage determines prognostic significance Results High is determinant therapeutic non-response HDACi, who did not respond exhibit massive tumor-associated (TAMs). TAM depletion reversed Mechanistically, impaired against cells epigenetically upregulating expression. Reciprocally, HDACi-upregulated polarized towards pro-tumor M2 phenotype SIRPα ligation. In tumor-bearing mice, monotherapy only marginally delayed progression, while concurrent neutralization exhibited potent anti-tumor re-educating TAMs tumoricidal phenotype. patients, found determine TAMs. Conclusions Our offers rationale targeting or blocking sensitize therapies

Language: Английский

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Harnessing p53 for targeted cancer therapy: new advances and future directions

Transcription, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 44

Published: March 3, 2025

The transcription factor p53 is the most frequently impaired tumor suppressor in human cancers. In response to various stress stimuli, activates of genes that mediate its tumor-suppressive functions. Distinctive characteristics outlined here enable a well-defined program involved cell cycle arrest, apoptosis, senescence, differentiation, metabolism, autophagy, DNA repair, anti-viral response, and anti-metastatic functions, as well facilitating autoregulation within network. This versatile, anti-cancer network governed chiefly by single protein represents an immense opportunity for targeted cancer treatment, since about half tumors retain unmutated p53. During last two decades, numerous compounds have been developed block interaction with main negative regulator MDM2. However, small molecule inhibitors MDM2 only induce therapeutically desirable apoptotic limited number types. Moreover, clinical trials monotherapies not met expectations revealed hematological toxicity characteristic adverse effect across this drug class. Currently, combination treatments are leading strategy enhancing efficacy reducing effects inhibitors. review summarizes efforts identify test therapeutics work synergistically Two types drugs emerged among used following treatments: first, modulators p53-regulated transcriptome (including chromatin modifiers), translatome, proteome, second, targeting downstream pathways such metabolic immune ferroptosis, growth signaling. Here, we current literature field, while also highlighting overarching principles could guide target selection future treatments.

Language: Английский

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HDAC inhibitor SAHA enhances antitumor immunity via the HDAC1/JAK1/FGL1 axis in lung adenocarcinoma

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(10), P. e010077 - e010077

Published: Oct. 1, 2024

Histone deacetylase (HDAC), a kind of protease that regulates gene expression by modifying protein acetylation levels, is usually aberrantly activated in tumors. The approved pan-HDAC inhibitors (HDACi) have exhibited clinical benefits for hematopoietic malignancies. Recently, HDACis emerged as enhancers antitumor immunity. However, the effect HDACs on tumor immune microenvironment lung adenocarcinoma (LUAD) and underlying mechanism largely unknown.

Language: Английский

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Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer

Biomolecules, Journal Year: 2024, Volume and Issue: 15(1), P. 15 - 15

Published: Dec. 26, 2024

Epigenetics encompasses reversible and heritable genomic changes in histones, DNA expression, non-coding RNAs that occur without modifying the nucleotide sequence. These play a critical role modulating cell function both healthy pathological conditions. Dysregulated epigenetic mechanisms are implicated various diseases, including cardiovascular disorders, neurodegenerative obesity, mainly cancer. Therefore, to develop innovative therapeutic strategies, research for compounds able modulate complex landscape of cancer is rapidly surging. Dietary phytochemicals, mostly flavonoids but also tetraterpenoids, organosulfur compounds, isothiocyanates, represent biologically active molecules found vegetables, fruits, medicinal plants, beverages. natural organic exhibit modulatory properties by influencing activity epigenetics key enzymes, such as methyltransferases, histone acetyltransferases deacetylases, methyltransferases demethylases. Due reversibility modifications they induce, their minimal adverse effects, potent regulatory activity, dietary phytochemicals hold significant promise antitumor agents warrant further investigation. This review aims consolidate current data on diverse effects six major flavonoid subclasses, well other context The goal identify new targets drug development, whether stand-alone treatments or combination with conventional approaches.

Language: Английский

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CRY1 fuels resistance to T cell-based immunotherapy in NANOGhigh cancers

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Cancer immunotherapies, including immune checkpoint blockade (ICB), have marked a significant breakthrough in cancer treatment but their clinical efficacy is limited immune-resistant tumors. Previously, we found that immunotherapy-mediated selection enriches tumors with both tumor-intrinsic and -extrinsic refractory phenotypes via the transcriptional induction of HDAC1 by NANOG. Here, identify CRY1 as critical target NANOG stabilizes Cyclin A MCL1 to promote stem cell-like property resistance cytotoxic T cell-mediated killing NANOG^high tumor cells through HDAC1-mediated epigenetic silencing APC3 TRIM17. Additionally, downregulates CXCL10 repression, thereby suppressing cell infiltration. Importantly, inhibition synergizes PD-1 adoptive transfer reducing growth converting into immune-sensitive Collectively, these findings highlight mediator NANOG/HDAC1 axis multiple properties suggest potential therapeutic target.

Language: Английский

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A promising future for breast cancer therapy with hydroxamic acid-based histone deacetylase inhibitors

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108169 - 108169

Published: Jan. 20, 2025

Language: Английский

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Synergistic strategies: histone deacetylase inhibitors and platinum-based drugs in cancer therapy

Expert Review of Anticancer Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

The synergistic combination of histone deacetylase inhibitors and platinum-based medicines represents a promising therapeutic strategy to efficacy overcome drug resistance in cancer therapy, necessitating comprehensive on their molecular interactions clinical potential. objective presented review is investigate the pathways platinum HDAC inhibitors. A literature from 2011 2024 was conducted across multiples databases like MEDLINE, PubMed, Google Scholar, Science Direct, Scopus official websites ClinicalTrial.gov explore publications inhibitors, drugs, therapies, revealing preliminary evidence innovative treatment strategies involving chemotherapeutics. Several new (IV) complexes, with inhibitory moieties better cytotoxicity profiles than conventional are also reviewed here. above has great potential treatment, however managing toxicity, dosage regimens, patient selection biomarkers problematic. More selective delivery techniques areas for future research. An adaptation toward changing landscapes, highlights combining serves concept personalized medicine, an deeper research still need time.

Language: Английский

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