Membrane-Active Thermoresponsive Block Copolymers Containing a Diacylglycerol-Based Segment: RAFT Synthesis, Doxorubicin Encapsulation, and Evaluation of Cytotoxicity against Breast Cancer Cells

Herein, we report the formation of drug delivery systems from original thermoresponsive block copolymers containing lipid-based segments. Two acrylate monomers derived from palmitic- or oleic-acid–based diacylglycerols (DAGs) were synthesized and polymerized by the reversible addition–fragmentation chain transfer (RAFT) method. Well-defined DAG-based polymers with targeted molar masses and narrow molar mass distributions were next used as macro-chain transfer agents (macro-CTAs) for the polymerization of N-isopropylacrylamide (NIPAAm) or N-vinylcaprolactam (NVCL). The obtained amphiphilic block copolymers were formed into polymeric nanoparticles (PNPs) with and without encapsulated doxorubicin and characterized. Their biological assessment indicated appropriate cytocompatibility with the representatives of normal cells. Furthermore, compared to the free drug, increased cytotoxicity and apoptosis or necrosis induction in breast cancer cells was documented, including a highly aggressive and invasive triple-negative MDA-MB-231 cell line.


Figure S5 .
Figure S5.FT-IR spectra for the synthesis route of monomer containing palmitic acid derivative (GlyP-A).

Figure S6 .
Figure S6.FT-IR spectra for the synthesis route of monomer containing oleic acid derivative (GlyO-A).

Figure S10 .
Figure S10.TG (top panels) and DTG curves (bottom panels) of the studied polymers and copolymers.

Figure S11 .
Figure S11.DSC curves (the second heating and cooling run) of the studied polymers and copolymers.

Figure S14 .
Figure S14.Evolution of transmittance measured by turbidimetry and number size distribution as a function of temperature for polymeric nanoparticles.

Figure S16 .
Figure S16.Fluorescence properties of polymers and corresponding polymeric nanoparticles.

Table S1 .
Thermal properties of the polymers.

Table S2 .
Evaluation of colloidal stability of polymeric nanoparticles.