Directing mineralization of ZnO nanoparticles in cyanobacterial liquid crystalline polysaccharides for cancer therapies.

Abstract

Effective cancer therapy faces significant challenges, including non-selective toxicity, limited structural stability, inconsistent nanoparticle (NP) morphology, and instability under varying biological conditions. These issues hindering targeted delivery and therapeutic efficacy. Previous approaches using polysaccharide-based nanomaterials have shown promise; however, problems such as inconsistent NP sizes and shapes, poor mechanical stability, and limited pH resilience restrict their clinical potential. This study hypothesized that sacran, a cyanobacterial liquid crystalline (LC) polysaccharide, can stabilize ZnO NPs, allowing for controlled mineralization, enhanced stability, and selective cytotoxicity. We developed ZnO nanocomposite xerogels in an LC sacran matrix, yielding block-like ZnO NPs (25-70 nm) with high surface-area-to-volume ratios that improve cellular uptake in tumor environments. Incorporating these NPs into chemically crosslinked sacran matrices resulted in a 3-fold increase in mechanical strength and a 10-fold improvement in swelling capacity compared to physically crosslinked systems. Additionally, the sacran-ZnO nanocomposites demonstrated robust stability under various pH conditions, indicating their resilience in diverse biological environments. Cytotoxicity assays revealed that higher concentrations of ZnO NP selectively increased toxicity toward human lung cancer cells (A549), with less impact on human dermal fibroblasts (HDFa). Moreover, HDFa successfully attached to and proliferated on the smooth surfaces of the xerogels, emphasizing their compatibility with normal cells. This highlights the potential of sacran-ZnO nanocomposite xerogels as cancer-selective therapeutic materials, offering stability and effectiveness even under varying biological conditions, while addressing key challenges associated with earlier NP-based therapies.