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

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.

Limitations of ion mobility spectrometry-mass spectrometry for the relative quantification of architectural isomeric polymers: A case study.

Since their discovery, cyclic polymers have attracted great interest because of their unique properties. Today, the preparation of these macrocyclic structures still remains a challenge for polymer chemists, and most of the preparation pathways lead to an inescapable contamination by linear by-products. As the properties of the polymers are closely related to their structure, it is of prime importance to be able to assess the architectural purity of a sample. METHODS: In this work, the suitability of ion mobility spectrometry-mass spectrometry (IMS-MS) for the quantification of two isomers was investigated. A cyclic poly(L-lactide) was prepared through photodimerization of its linear homologue. Since IMS-MS can be used to differentiate cyclic polymer ions from their linear analogues because of their more compact three-dimensional conformation, the present work envisaged the use of IMS-MS for the quantification of residual linear polymers within the cyclic polymer sample. RESULTS: Using the standard addition method to plot calibration curves, the fraction of linear contaminants in the sample was determined. By doing so, unrealistically high values of contamination were measured. CONCLUSIONS: These results were explained by an ionization efficiency issue. This work underlines some intrinsic limitations when using IMS-MS in the context of the relative quantification of isomers having different ionization efficiencies. Nevertheless, the linear-to-cyclic ratio can be roughly estimated by this method.

One Step Further in the Characterization of Synthetic Polymers by Ion Mobility Mass Spectrometry: Evaluating the Contribution of End-groups.

Several families of polymers possessing various end-groups are characterized by ion mobility mass spectrometry (IMMS). A significant contribution of the end-groups to the ion collision cross section (CCS) is observed, although their role is neglected in current fitting models described in literature. Comparing polymers prepared from different synthetic procedures might thus, be misleading with the current theoretical treatments. We show that this issue is alleviated by comparing the CCS of various polymer ions (polyesters and polyethers) as a function of the number of atoms in the macroion instead of the usual representation involving the degree of polymerization. Finally, we extract the atom number density from the spectra which gives us the possibility to evaluate the compaction of polymer ions, and by extension to discern isomeric polymers.

Polymers for Traveling Wave Ion Mobility Spectrometry Calibration.

One of the main issues when using traveling wave ion mobility spectrometry (TWIMS) for the determination of collisional cross-section (CCS) concerns the need for a robust calibration procedure built from referent ions of known CCS. Here, we implement synthetic polymer ions as CCS calibrants in positive ion mode. Based on their intrinsic polydispersities, polymers offer in a single sample the opportunity to generate, upon electrospray ionization, numerous ions covering a broad mass range and a large CCS window for different charge states at a time. In addition, the key advantage of polymer ions as CCS calibrants lies in the robustness of their gas-phase structure with respect to the instrumental conditions, making them less prone to collisional-induced unfolding (CIU) than protein ions. In this paper, we present a CCS calibration procedure using sodium cationized polylactide and polyethylene glycol, PLA and PEG, as calibrants with reference CCS determined on a home-made drift tube. Our calibration procedure is further validated by testing the polymer calibration to determine CCS of numerous different ions for which CCS are reported in the literature. Graphical Abstract ᅟ.

Synthesis and Characterization of Double Crystalline Cyclic Diblock Copolymers of Poly(ε-caprolactone) and Poly(l(d)-lactide) (c(PCL-b- PL(D)LA)).

The synthesis of symmetric cyclo poly(ε-caprolactone)-block-poly(l(d)-lactide) (c(PCL-b-PL(D)LA)) by combining ring-opening polymerization of ε-caprolactone and lactides and subsequent click chemistry reaction of the linear precursors containing antagonist functionalities is presented. The two blocks can sequentially crystallize and self-assemble into double crystalline spherulitic superstructures. The cyclic chain topology significantly affects both the nucleation and the crystallization of each constituent, as gathered from a comparison of the behavior of linear precursors and cyclic block copolymers. The stereochemistry of the PLA block does not have a significant effect on the nonisothermal crystallization of both linear and cyclo PCL-b-PDLA and PCL-b-PLLA copolymers.