Self-destructible polysaccharide nanocomposites with unlockable Au nanorods for high-performance photothermal therapy

Multifunctional organic/inorganic nanocomposites are highly attractive for effective biomedical applications. In this work, versatile types of self-destructible polysaccharide (dextran or pullulan) nanocomposites (denoted Au@PSa) with adjustable amounts of unlockable Au nanorods (Au NRs) were fabricated as highly efficient photothermal cancer therapy systems. Taking advantage of the acidic endosomes and high concentration of glutathione (GSH) present in cancer cells, the responsive self-destruction of Au@PSa nanocomposites could unlock the abundant encapsulated Au NRs within cells. Notably, the pullulan-based nanocomposites (denoted Au@Pul) demonstrated liver cell-targeting properties, which could enhance the therapeutic effects while minimizing side effects. The strong absorption of the unlocked Au NRs in the near-infrared region was utilized to examine the photothermal performance. The Au@PSa nanocomposites with a moderate amount of Au NRs in the matrix exhibited very impressive photothermal effects in tumor therapy, where the encapsulated Au NRs were unlocked in the tumor region to realize the observed high performance. The proposed system could be further extended, as the polysaccharides were functionalized with amino groups. The current work provides a facile strategy to construct flexible therapeutic platforms with responsive self-destruction features. A strategy that relies on polysaccharides and gold nanorods to realize cancer therapy shows promise in live animal studies. In photothermal therapy, nanoparticles in cancerous tissue convert laser light into heat and damage tumors while leaving surrounding healthy tissue unharmed. Nana Zhao and Fu-Jian Xu from the Beijing University of Chemical Technology in China and colleagues synthesized polysaccharide-based nanocapsules that can encapsulate photothermal gold nanorods (pullulan-gold nanocomposites), and simultaneously target asialoglycoprotein receptor overexpressed liver cancer cells. Using real-time confocal laser scanning microscopy, the team demonstrated that the nanocomposites rapidly accumulated around the nuclei of hepatoma cells, where acidic conditions dissolved the polysaccharide matrix and unleashed gold nanorods with the assistance of glutathione. Images taken after photothermal therapy in mice revealed massive shrinking of cancerous cells and fragmented nuclei, with no side effects on major organs. Versatile types of self-destructible polysaccharide nanocomposites with adjustable amounts of unlockable Au nanorods were fabricated for highly efficient photothermal cancer therapy systems.