MOLECULES
·
2020
·Vol. 25
·期 2
·407
·
IF 3.267
Jiaguo Li,Dian Xiao,Lianqi Liu,Fei Xie,Wei Li,Wei Sun,Xiaohong Yang,Xinbo Zhou
In this article, we report the design, synthesis, photodynamic properties, and in vitro evaluation of photoactivatable prodrug for the poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor Talazoparib. In order to yield a photoactivatable, inactive prodrug, photoactivatable protecting groups (PPGs) were employed to mask the key pharmacophore of Talazoparib. Our study confirmed the good stability and photolytic effect of prodrugs. A PARP-1 enzyme inhibition assay and PARylation experiment showed that the inhibitory activity of the prodrug was reduced 380 times and more than 658 times, respectively, which proved that the prodrug’s expected activity was lost after PPG protection. InBRCA1- andBRCA2-deficient cell lines, the inhibitory activity of the compound was significantly restored after ultraviolet (UV) irradiation. The results indicate that the photoactivatable prodrug strategy is an interesting approach for studying PARP inhibitors. Meanwhile, the described photoactivatable prodrug also provided a new biological tool for the mechanism research of PARP.Keywords:Talazoparib;PARP inhibitor;prodrug;o-nitro-benzyl;photoactivatable protecting groups
研究领域:
药物化学
·
肿瘤学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMBIOCHEM
·
2024
·
IF 2.6
Wen Fu,Zhongli Shao,Zhiping Xu,Zhong Li,Xusheng Shao
Graphical NP-TBZ is developed by covalently linking o -nitrobenzyl ( NP ) with thiabendazole ( TBZ ). Compound NP-TBZ can be controlled to release TBZ in dependent to light, which resulted in controllable in-vivo activity against wheat scab. It is promising for spatiotemporal controlled-release of TBZ in factual applications, posing a theoretical guidance in development of controlled-release pesticides. Pesticides are essential in agricultural development. Controlled-release pesticides have attracted great attentions. Base on a principle of spatiotemporal selectivity, we extended the photoremovable protective group (PRPG) into agrochemical agents to achieve controllable release of active ingredients. Herein, we obtained NP-TBZ by covalently linking o -nitrobenzyl ( NP ) with thiabendazole ( TBZ ). Compound NP-TBZ can be controlled to release TBZ in dependent to light. The irradiated and unirradiated NP-TBZ showed significant differences on fungicidal activities both in vitro and in vivo. In addition, the irradiated NP-TBZ displayed similar antifungal activities to the directly-used TBZ , indicating a factual applicability in controllable release of TBZ . Furthermore, we explored the action mode and microcosmic variations by SEM analysis, and demonstrated that the irradiated NP-TBZ retained a same action mode with TBZ against mycelia growth.
研究领域:
农业科学
·
植物保护
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULES
·
2019
·
IF 5.997
Sifan Ji,Lili Xu,Xiaohui Fu,Jing Sun,Zhibo Li
Because of the advantageous properties, the photoresponsive bioinspired polymers are of great interest for many applications. In this study, we synthesized a new family of photoresponsive poly(ethylene glycol)-block-poly(o-nitrobenzyl-l-glutamate) diblock copolymers, which can self-assemble into spherical micelles in aqueous solution. Upon UV irradiation, an interesting photoinduced morphology transition from spheres to cylinders was observed arising from the disruption of amphiphilicity induced by the cleavage of o-nitrobenzyl groups on the side chains. A couple of techniques including proton nuclear magnetic resonance (1H NMR) and ultraviolet–visible absorption spectra measurement (UV–vis) were used to track the process of photolysis. A systematic study on the effects of pH, molecular weights, and secondary structure on the self-assembly of diblock copolymers was performed. We demonstrate that the secondary conformation transition with pH variation dominates the sphere-to-cylinder transition. Remarkably, the hierarchical nanostructures with various dimensions can be obtained from preassembled units with the addition of metal ions.
研究领域:
材料科学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Jinhu Liu,Han Yang,Xiao Sang,Tong Gao,Zipeng Zhang,Shunli Fu,Huizhen Yang,Lili Chang,Xiaoqing Liu,Shuang Liang,Shijun Yuan,Suyun Wei,Yuxin Yang,Xiaoxin Yan,Xinke Zhang,Weiwei Mu,Yongjun Liu,Na Zhang
Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o -nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.
研究领域:
癌症研究
·
药学
·
纳米技术
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Kai Han,Wei-Na Yin,Jin-Xuan Fan,Feng-Yi Cao,Xian-Zheng Zhang
In this report, a UV sensitive, PEGylated PFSSTKTC (Pro-Phe-Ser-Ser-Thr-Lys-Thr-Cys) peptide was modified on quartz substrate to investigate the spatial controlled differentiation of stem cells. This substrate could restrict the cell adhesion due to the steric hindrance of PEG shell. With UV irradiation, PFSSTKTC became exposed owing to the breakage of o-nitrobenzyl group with the detachment of PEG shell. The irradiation boundary on substrate was stable in the long term. The in vitro osteogenic differentiation results revealed that under the site-specific irradiation, the mesenchymal stem cells (MSCs) could specifically differentiate into osteoblast under the induction of PFSSTKTC peptide. This photoactivatable biomaterial shows great potential for region controllable and precise MSCs differentiation.
研究领域:
生物材料
·
干细胞生物学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）