tert-Butoxycarbonyl-Modification Driven Disturbance of Molecular Ordering Enables High-Efficiency Dual Drugs Co-Assembly for Synergistic Tumor Inhibition DOI
Xuequan Zhang,

Xiaoxian Zhang,

Jiahui Zhu

и другие.

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

The development of carrier-free drug delivery systems (CDDS) for tailored combinations posed a significant challenge, particularly in achieving efficient co-assembly while maintaining therapeutic efficacy. Herein, we proposed strategy based on molecular engineering. Paclitaxel (PTX) and 7-ethyl-10-hydroxycamptothecin (SN38) were chemically modified with tert-butoxycarbonyl (BOC) groups. successful incorporation the BOC groups was confirmed by proton nuclear magnetic resonance mass spectrometry analyses. Further characterization using polarized light microscopy X-ray diffraction revealed that this modification significantly reduced crystallinity both drugs, simultaneously disrupting their original ordered stacking structure. Molecular dynamics simulations indicated increased spacing, density, expanded volume, resulting looser packing arrangement. This structural alteration enabled molecules to efficiently coassemble α-tocopherol succinate (α-TOS) into spherical nanoparticles at nearly predefined ratio. exhibited high loading capacity 52.66% remained stable 4 °C over 50 days. Notably, these displayed controllable release characteristics pH 5.0. Both vitro vivo studies demonstrated BOC-modified drugs retained bioactivity. When co-assembled α-TOS, synergistic antitumor effect suppressed tumor metastasis through downregulation matrix metalloproteinase-9 (MMP-9) expression. study provided solid theoretical foundation innovative approach CDDS, utilizing molecular-scale regulation co-assembly.

Язык: Английский

A computer-aided, carrier-free drug delivery system with enhanced cytotoxicity and biocompatibility: a universal model for multifunctional lung cancer therapy DOI
Zhonglei Wang,

Wenjing Xu,

Shizeng Lei

и другие.

Colloids and Surfaces B Biointerfaces, Год журнала: 2025, Номер 250, С. 114557 - 114557

Опубликована: Фев. 9, 2025

Язык: Английский

Процитировано

0
Adipose-targeted nanohybrid as a browning inducer for synergistic hyperthermia–pharmacotherapy of obesity DOI
Xiaoyang Han, Xin Zeng,

Shiwen Gao

и другие.

Journal of Colloid and Interface Science, Год журнала: 2025, Номер 687, С. 540 - 551

Опубликована: Фев. 15, 2025

Язык: Английский

Процитировано

0
Novel insights into taxane pharmacology: an update on drug resistance mechanisms, immunomodulation and drug delivery strategies DOI Creative Commons
Giovanni Luca Beretta, Giuliana Cassinelli, Giacomina Rossi

и другие.

Drug Resistance Updates, Год журнала: 2025, Номер 81, С. 101223 - 101223

Опубликована: Март 8, 2025

Taxanes are effective in several solid tumors. Paclitaxel, the main clinically available taxane, was approved early nineties, for treatment of ovarian cancer and later on, together with analogs docetaxel cabazitaxel, other malignancies. By interfering microtubule function impairing separation sister cells at mitosis, taxanes act as antimitotic agents, thereby counteracting high proliferation rate cells. The action goes beyond their because cellular targets, microtubules, participate multiple processes such intracellular transport cell shape maintenance. clinical efficacy is limited by development resistance mechanisms. Among these, extracellular vesicles have emerged new players. In addition, taxane metronomic schedules shows an impact on tumor microenvironment reflected antiangiogenic immunomodulatory effects, aspect growing interest considering inclusion regimens immunotherapeutics. Preclinical studies paved bases synergistic combinations both conventional targeted agents. A variety drug delivery strategies provided novel opportunities to increase activity. ability orchestrate different effects amenable modulation suggests options improve cures lethal

Язык: Английский

Процитировано

0
tert-Butoxycarbonyl-Modification Driven Disturbance of Molecular Ordering Enables High-Efficiency Dual Drugs Co-Assembly for Synergistic Tumor Inhibition DOI
Xuequan Zhang,

Xiaoxian Zhang,

Jiahui Zhu

и другие.

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

The development of carrier-free drug delivery systems (CDDS) for tailored combinations posed a significant challenge, particularly in achieving efficient co-assembly while maintaining therapeutic efficacy. Herein, we proposed strategy based on molecular engineering. Paclitaxel (PTX) and 7-ethyl-10-hydroxycamptothecin (SN38) were chemically modified with tert-butoxycarbonyl (BOC) groups. successful incorporation the BOC groups was confirmed by proton nuclear magnetic resonance mass spectrometry analyses. Further characterization using polarized light microscopy X-ray diffraction revealed that this modification significantly reduced crystallinity both drugs, simultaneously disrupting their original ordered stacking structure. Molecular dynamics simulations indicated increased spacing, density, expanded volume, resulting looser packing arrangement. This structural alteration enabled molecules to efficiently coassemble α-tocopherol succinate (α-TOS) into spherical nanoparticles at nearly predefined ratio. exhibited high loading capacity 52.66% remained stable 4 °C over 50 days. Notably, these displayed controllable release characteristics pH 5.0. Both vitro vivo studies demonstrated BOC-modified drugs retained bioactivity. When co-assembled α-TOS, synergistic antitumor effect suppressed tumor metastasis through downregulation matrix metalloproteinase-9 (MMP-9) expression. study provided solid theoretical foundation innovative approach CDDS, utilizing molecular-scale regulation co-assembly.

Язык: Английский

Процитировано

0