Ferroptosis inducers: A new frontier in cancer therapy

Bioorganic Chemistry, Год журнала: 2024, Номер 146, С. 107331 - 107331

Опубликована: Апрель 2, 2024

Язык: Английский

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Probing the Impact of Surface Functionalization Module on the Performance of Mitoxantrone Prodrug Nanoassemblies: Improving the Effectiveness and Safety

Nano Letters, Год журнала: 2024, Номер 24(12), С. 3759 - 3767

Опубликована: Март 13, 2024

Prodrug nanoassemblies are emerging as a novel drug delivery system for chemotherapy, comprising four fundamental modules: module, modification response and surface functionalization module. Among these modules, is an essential process to enhance the biocompatibility stability of nanoassemblies. Here, we selected mitoxantrone (MTO) module DSPE-PEG2K develop MTO prodrug We systematically evaluated effect ratios (10%, 20%, 40%, 60% prodrug, WDSPE-mPEG2000/Wprodrug) on The results indicated that 40% NPs significantly improved self-assembly cellular uptake Compared with solution, showed better tumor specificity pharmacokinetics, resulting in potent antitumor activity good safety profile. These findings highlighted pivotal role regulating performance cancer treatment.

Язык: Английский

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The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 14(3), С. 1400 - 1411

Опубликована: Сен. 30, 2023

The self-assembly prodrugs are usually consisted of drug modules, activation and assembly modules. Keeping the balance between efficacy safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies. This study designed four docetaxel (DTX) using disulfide bonds as different lengths branched-chain fatty alcohols (C16, C18, C20, C24). determined ability affected modules' sensitivity. extension carbon chains improved prodrugs' pharmacokinetic behavior while reducing cytotoxicity increased cumulative toxicity. use C20 can safety. These results provide great reference rational design

Язык: Английский

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Minor Changes in Response Modules Leading to a “U-Shaped” Conversion Rate of Docetaxel Prodrug Nanoassemblies

Nano Letters, Год журнала: 2023, Номер 24(1), С. 394 - 401

Опубликована: Дек. 26, 2023

The prodrug-based nanoassemblies offer an alternative to settle the deficiencies of traditional chemotherapy drugs. In this nanosystem, prodrugs typically comprise drug modules, modification and response modules. modules are crucial for facilitating accurate conversion at specific sites. work, we opted differentiated disulfide bonds as construct docetaxel (DTX) prodrug nanoassemblies. Interestingly, a subtle change in leads "U-shaped" rate DTX-prodrug Prodrug with least carbon numbers between bond ester (PDONα) offered fastest rate, resulting powerful treatment outcomes some unavoidable toxic effects. PDONβ, more numbers, possessed slow poor antitumor efficacy but good tolerance. With most PDONγ, it demonstrated moderate effect induced risk lethality. Our study explored function highlighted their importance development.

Язык: Английский

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Carrier-free poly(glycyrrhetinic acid)-facilitated celastrol-loaded nanoparticle for high-efficiency low-toxicity treatment of rheumatoid arthritis

Materials & Design, Год журнала: 2024, Номер 241, С. 112951 - 112951

Опубликована: Апрель 16, 2024

Rheumatoid arthritis (RA) is a complex autoimmune disease associated with synovial inflammation and articular cartilage destruction. Currently, high-efficiency low-toxicity management of this intractable highly urgent. Here, drug-backboned polymer, polyglycyrrhetinic acid (PGA), was synthesized through the condensation GA, principal anti-inflammatory component Glycyrrhiza glabra. PGA then used as therapeutic polyprodrug carrier to fabricate carrier-free PGA@Cel nanoparticles (NPs) for treating rheumatoid arthritis. The as-prepared NPs exhibited uniformly spherical morphology an average particle size approximately 180 nm celastrol (Cel) loading capacity around 4.5 %. Upon intravenous injection, demonstrated prolonged blood circulation, efficient accumulation at inflammatory joints extravasation via leaky vasculature subsequent cell-mediated sequestration (ELVIS) effect. present study enhanced rheumatic decay efficiency in rat models antigen-induced arthritis, while simultaneously minimizing off-target toxicity. Overall, our results elucidate that nanopolydrug platform provides promising strategy RA therapy.

Язык: Английский

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Rational engineering of cholesterol-modified prodrug nanoassemblies for improving the tumor selectivity and safety of mitoxantrone

Fundamental Research, Год журнала: 2024, Номер unknown

Опубликована: Июнь 1, 2024

Mitoxantrone (MTO) is an anthraquinone antitumor drug with potent therapeutic benefits. However, its clinical application restricted by the severe side effects stemming from poor tumor selectivity. In this study, MTO and cholesterol (CLS) were conjugated via a tumor-selective disulfide bond to obtain MTO-SS-CLS prodrug. Interestingly, could self-assemble into uniform nanoassemblies, addition of DSPE-PEG2K significantly improved self-assembly behavior stability. Moreover, compared solutions, bond-bridged nanoassemblies exhibited heightened selectivity pharmacokinetic properties. addition, prodrug tolerated dose safety without compromising effect. This research enriches pharmaceutical paves way for extensive application.

Язык: Английский

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Single-cell RNA sequencing revealed PPARG promoted osteosarcoma progression: based on osteoclast proliferation

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 28, 2025

Background Osteosarcoma (OS) is one of the most common primary malignant bone tumors, primarily originating from mesenchymal tissue. It notorious for its high invasiveness, disability rate, mortality and poor prognosis. In metastatic destruction can promote cancer progression, which closely related to osteoclast activation imbalance between osteoblasts osteoclasts. A large number studies confirmed that osteoclasts are an important part OS, play active role in destroying homeostasis promoting progress OS. Therefore, we conducted a detailed study at single cell level, aiming find new OS therapeutic targets prevent tumor progression local spread. Methods We analyzed single-cell sequencing data patients usedMonocle2, Cytotrace, Slingshot software analyze pseudo-sequential trajectory during progression. CellChat was used reveal communication cells. PySCENIC identify transcription factors Finally, further demonstrated results by RT-qPCR analysis, CCK-8 assay, wound healing Transwell etc. Results Through analysis identified highly specific subgroup, C2MKI67+ Osteoclast. The key signaling pathway APP top 1 factor PPARG this subgroup played essential roles proliferation differentiation. Given pivotal speculated these pathways could emerge as novel targets, offering innovative strategies treatment. Conclusion This enhanced our understanding through scRNA-seq. Furthermore, discovered amplifies proliferation, resulting excessive resorption degradation matrix, thereby creating favorable environment growth. By innovatively targeting PPARG, it affected thus progression; work offered insights directions clinical treatment patients.

Язык: Английский

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Self-Assembled Reduction-Responsive Nanoparticles Constructed from Dual Topoisomerase I/Ii Inhibitor for Efficient Breast Cancer Treatment

Опубликована: Янв. 1, 2025

Язык: Английский

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Effects of modification modules-adjusted intermolecular forces on docetaxel prodrug Nanoassemblies: From assembly mechanisms to in vivo fate

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113894 - 113894

Опубликована: Май 1, 2025

Язык: Английский

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Hydrophilic Ethylene Glycol Fragments: A Determinant Affecting the Therapeutic Index of Paclitaxel Prodrug Nanoassemblies

ACS Central Science, Год журнала: 2024, Номер 10(12), С. 2253 - 2265

Опубликована: Ноя. 20, 2024

Prodrug-based nanoassemblies are promising platforms for cancer therapy. Prodrugs typically consist of three main components: drug modules, intelligent response and modification modules. However, the available modules usually hydrophobic aliphatic side chains, which affect activation efficiency prodrugs. Herein, hydrophilic ethylene glycol fragments were inserted between important effects on assembly, release, therapeutic index prodrugs investigated. Notably, introduction affected intermolecular forces increased interaction hydrogen bonding. In addition, significantly improved redox release profiles, prodrug nanoassemblies. PTX-SS-OA NPs with exhibited sensitivity, enhanced cytotoxicity, superior antitumor efficacy. comparison, PTX-SS-OAL without showed limited sensitivity cytotoxicity but displayed better safety. Overall, fragment is a critical determinant in modulating nanoassemblies, contributes to development advanced nanodelivery systems.

Язык: Английский

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