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- Prodrug Systems (II): a perspective of Polymer-based Doxorubicin Prodrug systems towards chemotherapyPublication . Wang, Zhao; Olim, Filipe; Sun, Jingjing; Neves, Ana Rute; Mendes, Fátima; Tomás, Helena; Sheng, RuilongUtilizing biocompatible polymers as platforms to covalently conjugate with chemotherapeutics to construct polymer-based prodrugs and their nano drug delivery systems has attracted great attention in recent years. This perspective reviewed state-of-the-arts for polymer-based doxorubicin prodrugs and the related nanodelivery systems, including: (1) pH-responsive polymer-doxorubicin prodrugs/conjugates; (2) pH/redox dual responsive prodrugs/conjugates; (3) reactive oxygen species/hypoxia-responsive polymer-doxorubicin prodrugs; (4) tumor receptor targeting polymer prodrugs; (5) enzyme-responsive polymer-doxorubicin prodrugs. Finally, possible future perspectives were also stated and discussed.
- Prodrug Systems (I): Lipid-based Doxorubicin Prodrugs and their nanodelivery systemsPublication . Olim, Filipe; Neves, Ana Rute; Wang, Zhao; Sun, Jingjing; Tomás, Helena; Sheng, RuilongUsing natural lipids to covalently connect with antitumor agents to construct lipid-based molecular prodrugs and their nanosystems is a promising research frontier for sustainable medicinal chemistry, nanobiotechnology and tumor chemotherapy. This paper reviewed recent progress of lipid-based doxorubicin (molecular) prodrugs and their nanodelivery systems, including lipid-doxorubicin prodrugs, stimuli-responsive lipid-doxorubicin prodrugs, and lipid-doxorubicin prodrug-based drug co-delivery nanosystems. Additionally, possible future research outlooks in this field were also discussed.
- Self‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cellsPublication . Olim, Filipe; Neves, Ana Rute; Vieira, Mariana; Tomás, Helena; Sheng, RuilongDeveloping new easy-to-prepare functional drug delivery nanosystems with good storage stability, low hemotoxicity, as well as controllable drug delivery property, has attracted great attention in recent years. In this work, a cholesterol-based prodrug nanodelivery system is prepared by self-assembly of cholesterol-doxorubicin prodrug conjugates (Chol-Dox) and tocopherol polyethylene glycol succinate (TPGS) using thin-film hydration method. The Chol-Dox/TPGS assemblies (molar ratio 2:1, 1:1, and 1:2) are able to form nanoparticles with average hydrodynamic diameter of ≈140–214 nm, surface zeta potentials of ≈−24.2–−0.3 mV, and remarkable solution stability in 0.1 m PBS, 16 days). The Chol-Dox/TPGS assemblies show low hemotoxicity and different cytotoxicity profiles in breast cancer cells (MCF-7 and MDA-MB-231), which are largely dependent on the molar ratio of Chol-Dox and TPGS. The Chol-Dox/TPGS assemblies tend to enter into MCF-7 and MDA-MB-231 cells through non-Clathrin-mediated multiple endocytosis and lysosome-dependent uptake pathways, moreover, these nanoassemblies demonstrate lysosome-dependent intracellular localization, which is different from that of free DOX (nuclear localization). The results demonstrate that the Chol-Dox/TPGS assemblies are promising cholesterol-based prodrug nanomaterials for breast cancer chemotherapy. Practical Applications: This work demonstrates a lipid prodrug-based nanotherapeutic system. Herein the Chol-Dox/TPGS nanoassemblies could serve as promising and controllable cholesterol-based prodrug nanomaterials/nano-formulations for potential breast cancer chemotherapy.