Multicore, SDS-Based Polyelectrolyte Nanocapsules as Novel Nanocarriers for Paclitaxel to Reduce Cardiotoxicity by Protecting the Mitochondria.

The clinical application of paclitaxel (PTX), a widely used anticancer drug, is constrained by cardiac arrhythmias and disruptions in vascular homeostasis. To mitigate the non-specific, high toxicity of PTX towards cardiomyocytes, we propose the application of newly synthesized SDS-based polyelectrolyte multicore nanocapsules. This study aims to verify the hypothesis that SDS-based NCs can mitigate the cytotoxic effects of PTX on cardiac cells and serve as effective nanocarriers for this drug. We investigated two types of multicore NCs with differing polyelectrolyte coatings: poly-L-lysine (PLL) and a combination of PLL with poly-L-glutamic acid (PGA). The cytotoxicity of the formulated nanosystems was evaluated using HL-1 cardiomyocytes. Oxygraphy, flow cytometry, spectrophotometry, spectrofluorimetry, fluorescence microscopy, and RT-PCR were employed to assess disruptions in cardiac cellular homeostasis. Our data revealed that, among the tested NCs, SDS/PLL/PGA/PTX exhibited reduced cardiotoxicity and were better tolerated by HL-1 cardiomyocytes compared to SDS/PLL/PTX or PTX alone. In addition, SDS/PLL/PGA/PTX showed a marginal disruption of mitochondria's homeostasis, and no changes in APT level and intracellular calcium concentrations were observed. These findings underscore the potential of SDS-based multicore nanocarriers in anticancer therapy, particularly due to diminished cardiotoxicity and long-term stability in the biological fluids.