Self‐Assembly of Cholesterol‐Doxorubicin and TPGS into Prodrug‐Based Nanoparticles with Enhanced Cellular Uptake and Lysosome‐Dependent Pathway in Breast Cancer Cells

Developing new easy-to-prepare functional drug delivery nanosystems with good storage stability, low hemotoxicity, as well controllable 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 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, 1:2) are able to form nanoparticles average hydrodynamic diameter ≈140–214 nm, surface zeta potentials ≈−24.2–−0.3 mV, remarkable solution stability 0.1 m PBS, 16 days). show hemotoxicity different cytotoxicity profiles breast cancer cells (MCF-7 MDA-MB-231), which largely dependent on the molar Chol-Dox TPGS. tend enter into MCF-7 MDA-MB-231 through non-Clathrin-mediated multiple endocytosis lysosome-dependent uptake pathways, moreover, these nanoassemblies demonstrate intracellular localization, from that free DOX (nuclear localization). results promising nanomaterials for chemotherapy. Practical Applications: This work demonstrates lipid prodrug-based nanotherapeutic system. Herein could serve nanomaterials/nano-formulations potential