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- Green polymers toward nanobiotechnology(I): synthesis of glycopolypeptides and their analoguesPublication . Wang, Zhao; Neves, Ana Rute; Olim, Filipe; Tomás, Helena; Tang, Shi; Sheng, RuilongHarnessing natural-based renewable molecular resources to construct functional synthetic green polymers is a promising research frontier at the interface of sustainable/green chemistry, polymer chemistry and nanobiotechnology. As natural glycoprotein mimics/analogues and biocompatible building blocks of nanobio- materials, synthetic functional glycopolypeptides and their structural/functional analogues have attracted great attentions in recent years. This mini-perspective article reviewed current synthetic strategies and methods of glycopolypeptides and their analogues. The pros and cons of the synthesis protocols were discussed, moreover, possible future perspectives in this field were also stated.
- 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.