Design of naturally inspired jellyfish-shaped cyclopolylactides to manage osteosarcoma cancer stem cells fate

Romain Liénard; Monica Montesi; Silvia Panseri; Samuele Maria Dozio; Fabiana Vento; Placido G Mineo; Anna Piperno; Julien De Winter; Olivier Coulembier; Angela Scala

doi:10.1016/j.msec.2020.111291

Design of naturally inspired jellyfish-shaped cyclopolylactides to manage osteosarcoma cancer stem cells fate

Mater Sci Eng C Mater Biol Appl. 2020 Dec:117:111291. doi: 10.1016/j.msec.2020.111291. Epub 2020 Jul 24.

Authors

Affiliations

¹ Center of Innovation and Research in Materials and Polymers (CIRMAP), Laboratory of Polymeric and Composite Materials, University of Mons, Place du Parc 23, 7000 Mons, Belgium; Interdisciplinary Center for Mass Spectrometry (CISMa), Organic Synthesis and Mass Spectrometry Laboratory, University of Mons, Place du Parc 23, 7000 Mons, Belgium.
² CNR-ISTEC, Institute of Science and Technology for Ceramics, National Research Council of Italy, Via Granarolo 64, 48018 Faenza, RA, Italy.
³ Department of Chemical Sciences, University of Catania, Viale A. Doria, 95125 Catania, Italy.
⁴ Department of Chemical Sciences, University of Catania, Viale A. Doria, 95125 Catania, Italy; CNR-IPCB Institute of Polymers, Composites and Biomaterials, Via P. Gaifami 18, I-95126 Catania, Italy.
⁵ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
⁶ Interdisciplinary Center for Mass Spectrometry (CISMa), Organic Synthesis and Mass Spectrometry Laboratory, University of Mons, Place du Parc 23, 7000 Mons, Belgium.
⁷ Center of Innovation and Research in Materials and Polymers (CIRMAP), Laboratory of Polymeric and Composite Materials, University of Mons, Place du Parc 23, 7000 Mons, Belgium.
⁸ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy. Electronic address: ascala@unime.it.

PMID: 32919652
DOI: 10.1016/j.msec.2020.111291

Abstract

We report the synthesis, characterization and biological profile of new bis-triazoled cyclopolylactides (c-PLA, c-PLA-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 synthetized by click ring-closure of well-defined α,ω-heterodifunctional linear precursors, followed by quaternarization of N₃-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 till 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: Cancer stem cells; Click chemistry; Cyclo-PLA; Osteosarcoma; ROP; Salinomycin.

MeSH terms

Bone Neoplasms*
Cell Line, Tumor
Folic Acid
Humans
Nanoparticles*
Neoplastic Stem Cells
Osteosarcoma* / drug therapy
Polyethylene Glycols

Substances

Polyethylene Glycols
Folic Acid