Research Progress of Disulfide Bond Based Tumor Microenvironment Targeted Drug Delivery System

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 7547 - 7566

Опубликована: Июль 1, 2024

Abstract: Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, narrow therapeutic window, unfavorable pharmacokinetic properties. To solve above problems, target drug delivery tumor cells, reduce side effects drugs, an anti-tumor system based on microenvironment has become focus research in recent years. The construction reduction-sensitive nanomedicine disulfide bonds attracted much attention. Disulfide good reductive responsiveness can effectively high glutathione (GSH) levels environment, enabling precise delivery. further enhance targeting accelerate release, are often combined with pH-responsive nanocarriers highly expressed ligands cells construct systems. connect molecules polymer system, as well between different carrier molecules. This article summarized systems (DDS) that researchers constructed years bond microenvironment, cleavage-triggering conditions, various loading strategies, design. In this review, we also discuss controlled release mechanisms these DDS clinical applicability challenges faced translation. Keywords: bond, systems, GSH/ROS

Язык: Английский

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Programable Prodrug Nanomodulator Targets Tumor Redox Homeostasis Imbalance to Amplify Disulfidptosis and Immunogenic Pyroptosis for Breast Tumor Immunotherapy

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

Abstract Despite the great potential of photodynamic therapy (PDT), its success remains compromised by abnormal redox homeostasis tumor cells, which supports survival, growth, and resistance to oxidative therapeutic interventions neutralizing reactive oxygen species (ROS). To overcome this barrier, a multifunctional prodrug nanomodulator (Pro@FLNC) is designed induce disulfidptosis immunogenic pyroptosis trigger an antitumor immune response. Pro@FLNC features core–shell structure where ursolic acid (UA) Chlorin e6 (Ce6) are conjugated via GSH‐responsive linker encapsulated in DSPE‐PEG‐FA lipid shell for enhanced stability, biocompatibility, tumor‐specific targeting. Within microenvironment (TME), depletes intracellular GSH, disrupts homeostasis, releases Ce6 UA, triggering stress mitochondrial dysfunction. These mechanisms amplify ROS production, promote peroxidation, initiate disulfidptosis, evidenced increased SLC7A11 expression F‐actin collapse. Elevated levels metabolic imbalance‐triggered further activate pyroptosis, releasing damage‐associated molecular patterns (DAMPs) that stimulate dendritic cell maturation cytotoxic T‐cell activation. Together, reshapes TME, reduces immunosuppressive promotes CD8 + infiltration, effectively suppressing primary tumors metastases. This programmed offers promising strategy enhance PDT immunotherapy advanced breast cancer.

Язык: Английский

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Stimulus‐Responsive Nano‐Prodrug Strategies for Cancer Therapy: A Focus on Camptothecin Delivery

Small Methods, Год журнала: 2023, Номер 8(8)

Опубликована: Дек. 12, 2023

Camptothecin (CPT) is a highly cytotoxic molecule with excellent antitumor activity against various cancers. However, its clinical application severely limited by poor water solubility, easy inactivation, and severe toxicity. Structural modifications nanoformulations represent two crucial avenues for camptothecin's development. the potential further structural limited, camptothecin nanoparticles fabricated via physical loading have drawbacks of low drug leakage. Prodrug-based CPT shown unique advantages, including increased loading, reduced burst release, improved bioavailability, minimal toxic side effects. Stimulus-responsive nano-prodrugs that respond to endogenous or exogenous stimuli introducing activatable linkers achieve spatiotemporally responsive release at tumor site. This review comprehensively summarizes latest research advances in stimulus-responsive nano-prodrugs, preparation strategies, mechanisms, their applications cancer therapy. Special focus placed on mechanisms characteristics treatment. Furthermore, prodrugs are discussed. Finally, challenges future directions be valuable readers engaged prodrug expected.

Язык: Английский

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Ultrasound-Controlled Prodrug Activation: Emerging Strategies in Polymer Mechanochemistry and Sonodynamic Therapy

ACS Applied Bio Materials, Год журнала: 2024, Номер unknown

Опубликована: Май 2, 2024

Ultrasound has gained prominence in biomedical applications due to its noninvasive nature and ability penetrate deep tissue with spatial temporal resolution. The burgeoning field of ultrasound-responsive prodrug systems exploits the mechanical chemical effects ultrasonication for controlled activation prodrugs. In polymer mechanochemistry, materials scientists exploit sonomechanical effect acoustic cavitation mechanochemically activate force-sensitive On other hand, researchers sonodynamic therapy adopt fundamentally distinct methodologies, utilizing sonochemical (e.g., generation reactive oxygen species) ultrasound presence sonosensitizers induce transformations that This cross-disciplinary review comprehensively examines these two divergent yet interrelated approaches, both which originated from cavitation. It highlights molecular design strategies potential diverse therapeutic contexts, chemotherapy immunotherapy gene methods, discusses future directions this rapidly advancing domain.

Язык: Английский

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Leading prodrug strategies for targeted and specific release

Future Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 4

Опубликована: Март 14, 2025

Язык: Английский

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Dual‐Stimuli‐Activatable Hybrid Prodrug for the Self‐Immolative Delivery of an Anticancer Agent and Hydrogen Sulfide with Turn‐On Fluorescence

Chemistry - A European Journal, Год журнала: 2023, Номер 29(66)

Опубликована: Сен. 4, 2023

Stimuli-responsive fluorogenic prodrugs are advantageous for the targeted drug delivery enabling real-time non-invasive monitoring with turn-on fluorescence. We report herein dual-stimuli (ROS and CA)-responsive thiocarbamate-based prodrug (AM-TCB) of naphthalimide-based anticancer agent amonafide along gasotransmitter hydrogen sulfide (H2 S). A carbamate-based AM-CB was also designed, capable releasing without any H2 S. The were synthesized using multi-step organic synthesis. UV-Vis fluorescence spectroscopic studies revealed selective reactivity boronate ester group towards ROS (primarily O2 ) release COS/CO2 via self-immolative processes. Hydrolysis generated COS by carbonic anhydrase (CA) produces While AM-TCB retained activity free in cancer cells (MDA-MB-231 HeLa), unlike amonafide, it enhanced cellular viability non-malignant (HEK-293). Fluorescence imaging HeLa simultaneous S from Western blot further cytoprotective effects released AM-TCB. present adjuvant strategy therefore would be helpful future ameliorating drug-induced side-effects.

Язык: Английский

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Stimuli-Responsive Prodrugs with Self-Immolative Linker for Improved Cancer Therapy

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 279, С. 116928 - 116928

Опубликована: Сен. 30, 2024

Язык: Английский

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Esterase-Responsive Fluorogenic Prodrugs of Aldose Reductase Inhibitor Epalrestat: An Innovative Strategy toward Enhanced Anticancer Activity

ACS Applied Bio Materials, Год журнала: 2024, Номер 7(10), С. 6542 - 6553

Опубликована: Авг. 15, 2024

In addition to the conventional chemotherapeutic drugs, potent inhibitors of key enzymes that are differentially overexpressed in cancer cells and associated with its progression often considered as drugs choice for treating cancer. Aldose reductase (AR), which is primarily complications diabetes, known be closely related development drug resistance. Epalrestat (EPA), an FDA-approved drug, a inhibitor AR exhibits anticancer activity. However, poor pharmacokinetic properties limit bioavailability therapeutic benefits. We report herein first examples esterase-responsive turn-on fluorogenic prodrugs sustained release EPA fluorescence readout. Carboxylesterases several organ-specific help selective uncaging from prodrugs. The were synthesized using multistep organic synthesis successfully characterized. Absorption emission spectroscopic studies indicated successful activation presence porcine liver esterase (PLE) under physiological condition. HPLC revealed simultaneous both fluorophore over time mechanistic insights. While inhibitory potential released toward enzyme was validated aqueous medium, activity studied representative cervical cell line. Interestingly, our results can significantly enhance EPA. Finally, process by intracellular esterases cellular medium measuring microscopy. Therefore, present study highlights rational EPA, will better potential.

Язык: Английский

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pH/ROS co-triggered degradable polyprodrug as self-amplified drug self-delivery system for tumor-specific doxorubicin delivery

Colloids and Surfaces A Physicochemical and Engineering Aspects, Год журнала: 2025, Номер unknown, С. 136094 - 136094

Опубликована: Янв. 1, 2025

Язык: Английский

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Carrier-free nano-prodrugs for enhanced cancer therapy: stimuli-responsive design and applications

Polymer Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Язык: Английский

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