Endoperoxide‐enhanced self‐assembled ROS producer as intracellular prodrugs for tumor chemotherapy and chemodynamic therapy

Exploration, Journal Year: 2024, Volume and Issue: 4(4)

Published: Feb. 9, 2024

Abstract Prodrug‐based self‐assembled nanoparticles (PSNs) with tailored responses to tumor microenvironments show a significant promise for chemodynamic therapy (CDT) by generating highly toxic reactive oxygen species (ROS). However, the insufficient level of intracellular ROS and limited drug accumulation remain major challenges further clinical transformation. In this study, PSNs delivery artesunate (ARS) are demonstrated designing pH‐responsive ARS‐4‐hydroxybenzoyl hydrazide (HBZ)‐5‐amino levulinic acid (ALA) (AHA NPs) self‐supplied excellent chemotherapy CDT. The greatly improved loading capacity generation from endoperoxide bridge using electron withdrawing group attached directly C10 site artesunate. ALA ARS‐HBZ could be released AHA NPs under cleavage hydrazone bonds triggered acidic surroundings. Besides, increased heme in mitochondria, promoting lipid peroxidation anti‐tumor effects. Our study ARS through chemical modification, pointing out potential applications fields.

Language: Английский

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A Trisulfide Bond Containing Biodegradable Polymer Delivering Pt(IV) Prodrugs to Deplete Glutathione and Donate H₂S to Boost Chemotherapy and Antitumor Immunity

ACS Nano, Journal Year: 2024, Volume and Issue: 18(11), P. 7852 - 7867

Published: March 4, 2024

The clinical application of cisplatin (CisPt) is limited by its dose-dependent toxicity. To overcome this, we developed reduction-responsive nanoparticles (NP(3S)s) for the targeted delivery a platinum(IV) (Pt(IV)) prodrug to improve efficacy and reduce NP(3S)s could release Pt(II) hydrogen sulfide (H2S) upon encountering intracellular glutathione, leading potent anticancer effects. Notably, induced DNA damage activated STING pathway, which known promoter T cell activation. Comparative RNA profiling revealed that outperformed CisPt in enhancing immunity, antitumor oxidative stress pathways. In vivo experiments showed accumulated tumors, promoting CD8+ infiltration boosting immunity. Furthermore, exhibited robust while minimizing CisPt-induced liver Overall, results indicate hold great promise translation due their low toxicity profile activity.

Language: Английский

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Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle–mRNA formulation

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(22)

Published: May 21, 2024

Current treatment options for diabetic wounds face challenges due to low efficacy, as well potential side effects and the necessity repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid nanoparticle (TS LNP)-mRNA therapy accelerate wound healing by repairing reprogramming microenvironment of wounds. A library reactive oxygen species (ROS)-responsive TS LNPs was designed developed encapsulate interleukin-4 (IL4) mRNA. TS2-IL4 LNP-mRNA effectively scavenges excess ROS at site induces expression IL4 in macrophages, promoting polarization from proinflammatory M1 anti-inflammatory M2 phenotype site. In model db/db mice, with this significantly accelerates enhancing formation an intact epidermis, angiogenesis, myofibroblasts. Overall, platform not only provides safe, effective, convenient therapeutic strategy but also holds great clinical translation both acute chronic care.

Language: Английский

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Tailoring carrier-free nanocombo of small-molecule prodrug for combinational cancer therapy

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 352, P. 256 - 275

Published: Oct. 25, 2022

Language: Английский

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Taxanes prodrug-based nanomedicines for cancer therapy

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 348, P. 672 - 691

Published: June 21, 2022

Language: Английский

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A naphthalimide-based fluorescent probe with mitochondria targeting for GSH sensing and cancer cell recognition

Dyes and Pigments, Journal Year: 2023, Volume and Issue: 211, P. 111089 - 111089

Published: Jan. 9, 2023

Language: Английский

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Self-assembly of chlorogenic acid into hydrogel for accelerating wound healing

Colloids and Surfaces B Biointerfaces, Journal Year: 2023, Volume and Issue: 228, P. 113440 - 113440

Published: July 4, 2023

Language: Английский

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Satellite‐Type Sulfur Atom Distribution in Trithiocarbonate Bond‐Bridged Dimeric Prodrug Nanoassemblies: Achieving Both Stability and Activatability

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

Published: Nov. 21, 2023

Abstract Homodimeric prodrug nanoassemblies (HDPNs) hold promise for improving the delivery efficiency of chemo‐drugs. However, key challenge lies in designing rational chemical linkers that can simultaneously ensure stability, self‐assembly and site‐specific activation prodrugs. The “in series” increase sulfur atoms, such as trisulfide bond, improve assembly stability HDPNs to a certain extent, but limits Herein, trithiocarbonate bond ( ─ SC(S)S ), with stable “satellite‐type” distribution is developed via insertion central carbon atom bonds. effectively addresses existing predicament by homodimeric prodrugs while maintaining on‐demand bioactivation. Furthermore, inhibits antioxidant defense system, leading up‐regulation cellular ROS apoptosis tumor cells. These improvements endow vivo longevity specificity, ultimately enhancing therapeutic outcomes. is, therefore, promising overcoming bottleneck efficient oncological therapy.

Language: Английский

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A computer-aided, heterodimer-based “triadic” carrier-free drug delivery platform to mitigate multidrug resistance in lung cancer and enhance efficiency

Journal of Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 677, P. 523 - 540

Published: Aug. 14, 2024

Language: Английский

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Tumor microenvironment stimuli-responsive lipid-drug conjugates for cancer treatment

International Journal of Pharmaceutics, Journal Year: 2023, Volume and Issue: 639, P. 122942 - 122942

Published: April 9, 2023

Language: Английский

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