Design of naturally inspired jellyfish-shaped cyclopolylactides to manage osteosarcoma cancer stem cells fate
- 30 November 2020
- journal article
- research article
- Published by Elsevier BV in Materials Science and Engineering: C
- Vol. 117, 111291
- https://doi.org/10.1016/j.msec.2020.111291
Abstract
We report the synthesis, characterization and biological profile of new bis-triazoled cyclopolylactides (c-PLA, cPLA-FA, c-PLA-Rhod) obtained by an optimized combination of ROP and click chemistry reactions. Cyclo-PLA having a number average molecular weight of 6000 g mol(-1) and a polydispersity index of 1.52 was synthesized by click ring-closure of well-defined alpha,omega-heterodifunctional linear precursors, followed by quaternarization of N-3-triazole nodes, and subsequent CuAAC with azido-folate and azido-rhodamine yielding jellyfish-shaped c-PLA-FA and c-PLA-Rhod. Salinomycin (Sal) was loaded into jellyfish-shaped c-PLA-FA and c-PLA-Rhod nanoparticles (NPs) by nanoprecipitation, with a good encapsulation efficiency (79% and 84%, respectively) and loading content (7.1% and 7.6%, respectively). The biological studies focused on their antiproliferative effects on osteosarcoma bulk MG63 and cancer stem cells (CSCs). The cycloPLA-based NPs, with a size ranging between 125 and 385 nm, killed CSCs and MG63, with a higher efficacy on CSCs; they (unloaded or Sal-loaded) evoked on CSCs a cellular response similar to the payload, with a higher effect than the free Sal. Internalization studies indicated a fast cellular uptake (within 2 h) and sarcospheres remained fluorescent fill 72 h. To the best of our knowledge, this is the first study reporting anti-CSCs properties of cycloPLA with jellyfish architecture and we believe could contribute to the development of effective strategies for osteosarcoma targeting.Keywords
This publication has 50 references indexed in Scilit:
- Cyclic Block Copolymers for Controlling Feature Sizes in Block Copolymer LithographyACS Nano, 2012
- Salinomycin as a Drug for Targeting Human Cancer Stem CellsJournal of Biomedicine and Biotechnology, 2012
- Salinomycin inhibits osteosarcoma by targeting its tumor stem cellsCancer Letters, 2011
- Red‐Emitting Rhodamine Dyes for Fluorescence Microscopy and NanoscopyChemistry – A European Journal, 2009
- Cyclic polymers: Synthetic strategies and physical propertiesJournal of Polymer Science Part A: Polymer Chemistry, 2009
- Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput ScreeningCell, 2009
- Synthetic approaches for the preparation of cyclic polymersChemical Society Reviews, 2009
- Characterization of stem cell attributes in human osteosarcoma cell linesCancer Biology & Therapy, 2009
- Dependence of Pharmacokinetics and Biodistribution on Polymer Architecture: Effect of Cyclic versus Linear PolymersJournal of the American Chemical Society, 2009
- Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug contentInternational Journal of Pharmaceutics, 2007