GSH-Responsive Heterodimeric Dual-Targeted Nanomedicine Modulates EMT to Conquer Paclitaxel-Induced Invasive Breast Cancer Metastasis DOI
Ying Chen, Yao Chen, Hong Xu

и другие.

Bioconjugate Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

Paclitaxel (PTX), although effective against primary breast cancer, presents formidable clinical challenges due to severe toxicity and pro-metastatic potential, a critical concern as distant metastasis causes 90% of cancer-related deaths. To address these limitations, we designed prepared tumor microenvironment-responsive nanoprodrug, PTX-SS-3'HPT@RGD-HA NPs, that engineered RGD peptide-modified hyaluronic acid (HA) nanocarriers encapsulating the antimetastatic 3'-hydroxy pterostilbene (3'HPT) PTX heterodimer linked by glutathione (GSH)-cleavable disulfide bond. These nanoparticles targeting CD44 αvβ receptors overexpressed in aggressive cancer cells synergized enhanced permeability retention effects with receptor-mediated endocytosis, facilitating superior tumor-specific drug deposition GSH-activated payload release vitro vivo. Moreover, NPs achieved excellent growth inhibition while mitigating systemic metastatic risks 4T1 tumor-bearing mice. Mechanistically, 3'HPT counteracted PTX-induced epithelial-mesenchymal transition downregulating MMP-9/N-cadherin restoring E-cadherin expression, thereby neutralizing PTX-triggered effects. This study pioneers dual-targeted, toxicity-shielding nanoplatform simultaneously improves therapeutic efficacy addresses chemotherapy-driven metastasis, offering revolutionary strategy for managing highly invasive cancer.

Язык: Английский

Water‐Dispersible MXene Governs Glycolysis for Cancer Synergistic Therapy DOI
Jinfeng Liu,

Yuwen Gong,

Dandan Wang

и другие.

Small, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Abstract Targeted delivery of glucose oxidase (GOx) using MXene remains a great challenge due to its poor dispersion and susceptibility oxidation, the hypoxia high glutathione (GSH) contents make situation even more worrying. Herein, bovine serum albumin‐mediated non‐chemical modification strategy is developed, endowing titanium carbide with long‐time water‐dispersion further integrating it as glycolysis‐controllable therapy system without any chemotherapeutic agents. The also constructs an effective O 2 cycling GSH degradation pathway, which fundamentally adjusts tumor microenvironment greatly elevates both in vivo vitro effects. Reactive oxygen species are generated disrupt balance oxidative stress. Moreover, reduced efficiency mitochondrial energy production significantly inhibits level glycolysis hinders supply. study presents cancer treatment combining starvation/photothermal therapy, has superior anti‐cancer effects dual reducing levels diminishing cellular capacity.

Язык: Английский

Процитировано

0
Emergence of Small Nucleic Acids as Drugs in Precision Medicine DOI
Xing Cheng, Yan Wang,

Tingting Zhang

и другие.

Clinical Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Small nucleic acid drugs including antisense oligonucleotides, small interfering RNAs, microRNAs, and aptamers, among others, have revolutionized the pharmaceutical industry in 21st century, offering novel therapeutic strategies for a myriad of diseases through precise gene expression regulation or protein synthesis modulation. As December 2024, 19 been approved globally, with applications primarily treating rare hereditary conditions, metabolic diseases, ophthalmological disorders, demonstrating great clinical potential. This review provides an overview classification, mechanism action, technical challenges, addressing drugs, focus on indications market‐available aiming to equip healthcare professionals thorough understanding practical guidance their utilization.

Язык: Английский

Процитировано

0
GSH-Responsive Heterodimeric Dual-Targeted Nanomedicine Modulates EMT to Conquer Paclitaxel-Induced Invasive Breast Cancer Metastasis DOI
Ying Chen, Yao Chen, Hong Xu

и другие.

Bioconjugate Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

Paclitaxel (PTX), although effective against primary breast cancer, presents formidable clinical challenges due to severe toxicity and pro-metastatic potential, a critical concern as distant metastasis causes 90% of cancer-related deaths. To address these limitations, we designed prepared tumor microenvironment-responsive nanoprodrug, PTX-SS-3'HPT@RGD-HA NPs, that engineered RGD peptide-modified hyaluronic acid (HA) nanocarriers encapsulating the antimetastatic 3'-hydroxy pterostilbene (3'HPT) PTX heterodimer linked by glutathione (GSH)-cleavable disulfide bond. These nanoparticles targeting CD44 αvβ receptors overexpressed in aggressive cancer cells synergized enhanced permeability retention effects with receptor-mediated endocytosis, facilitating superior tumor-specific drug deposition GSH-activated payload release vitro vivo. Moreover, NPs achieved excellent growth inhibition while mitigating systemic metastatic risks 4T1 tumor-bearing mice. Mechanistically, 3'HPT counteracted PTX-induced epithelial-mesenchymal transition downregulating MMP-9/N-cadherin restoring E-cadherin expression, thereby neutralizing PTX-triggered effects. This study pioneers dual-targeted, toxicity-shielding nanoplatform simultaneously improves therapeutic efficacy addresses chemotherapy-driven metastasis, offering revolutionary strategy for managing highly invasive cancer.

Язык: Английский

Процитировано

0