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

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

A cuproptosis-based nanomedicine suppresses triple negative breast cancers by regulating tumor microenvironment and eliminating cancer stem cells DOI
Chen Xiao, Xing Wang, Shiyou Li

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 313, P. 122763 - 122763

Published: Aug. 17, 2024

Language: Английский

Citations

20
Gold nanocomposites in colorectal cancer therapy: characterization, selective cytotoxicity, and migration inhibition DOI
K. Tan, Le Yi Chia, Marwan Abdelmahmoud Abdelkarim Maki

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

Citations

0
Porous Fe/Cu Nanoreactor with Dual Insurance Design for Precision Chemotherapy and Chemodynamic Therapy DOI
Xianyu Zhu,

Lingli Gao,

Yanbo Zheng

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Abstract Poor prognosis and chemotherapy response stem from difficulties in precise targeting the lack of effective synergistic treatments. Nanozymes show promising potential tumor chemodynamic therapy (CDT) by catalyzing hydrogen peroxide (H₂O₂) decomposition glutathione depletion microenvironment (TME). However, integrating with CDT remains challenging. In this study, a porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) is developed for co‐loading humanized 3F8 anti‐GD2 disialoganglioside antibody (3F8) novel pyridazinone‐based chemotherapeutic agent (IMB), forming nanoreactor (3F8@FeCuNPs@IMB) targeted CDT. The responds specifically to acidic TME as primary insurance, allowing controlled release IMB at site. coating on surface acts secondary minimizing drug leakage during delivery process ensuring chemotherapy. Furthermore, FeCuNPs act peroxidase‐like (POD) oxidase‐like (GSHOX) enzymes, hydroxyl radical (•OH) generation depleting excess GSH, enhancing results vitro vivo indicate that dual insurance designed 3F8@FeCuNPs@IMB offers prospect targeted, precise, combination against melanoma.

Language: Английский

Citations

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

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

Citations

0