Small molecule prodrugs self-assembled nano-delivery systems with tumor responsive linkages are emerging as an effective platform. However, the heterogeneity of tumor microenvironment may limit the anti-tumor effect of prodrug nanomedicines with a single response module. Here, we chose disulfide bond as the response module and branched chain alcohol as the self-assembly modification module to construct a single-responsive prodrug. We also constructed a double-responsive paclitaxel prodrug combining triglyceride and disulfide bond, taking into account of the highly expressed lipase and glutathione levels in tumor cells. The results showed that the anti-tumor effect of single-responsive branched chain alcohol modified prodrug nanoparticles was inferior to triglyceride prodrug nanoparticles with dual response modules. The triglyceride structure can not only serve as a self-assembly modification module, but also serve as a response module for intelligent drug release in tumor. Such dual roles will facilitate the efficient delivery of small molecule self-assembled prodrugs to tumor sites.
Yao He,Zexiang Bi,Qiang Zhang,Shuang Lu,Zhijian Huang,Xiaochao Zhang,Xu Li,Jinxiang Dong
Isononanol, a branched aliphatic alcohol, is derived from isobutylene upgradation, encompassing dimerization and hydroformylation. Branched surfactants exhibit lower surface tension, superior wettability, and rapid defoaming compared to linear surfactants. Isononanol (C9–OH) with abundant methyl branching can serve as a hydrophobic tail of branched surfactants, suffering from insufficient lipophilicity due to its short effective chain length. This paper proposes a strategy to extend the hydrophobic tail by grafting one propylene oxide (P1) or butylene oxide (B1) to increase chain length and branching degree with the aim of synthesizing extended multibranched alcohols C9P1–OH and C9B1–OH with purities of 95.3 and 97.2%, respectively. Subsequently, a series of extended multibranched alcohol polyether nonionic surfactants (C9P1En and C9B1En) were synthesized by ethoxylation, with their structures confirmed by Fourier-transform infrared (FT-IR) and 1H NMR and their surfactant properties systematically investigated. The findings indicate that C9P1En and C9B1En exhibited lower γCMC values compared to the isononanol polyether surfactant (C9En), which allows for rapid wetting on a hydrophobic surface, especially C9B1E6 with an initial contact angle of only 54° compared to 80° for C9E6. Also remarkable is the rapid defoaming performance, with C9B1E6 having less than 0.1% of the initial foam volume but C9E6 having up to 50.1% foam volume after 30 s. These surfactant performances provide significant benefits for the potential application of branched nonionic surfactants in the industrial cleaning field.
危险品化学品经营许可证（带存储）