92 / 2023-09-27 19:47:05

Nanomedicines Against Cancer and Inflammatory Diseases Based on Phosphorous Dendrimers and Dendrons

phosphorous dendrimers and dendrons; drug/gene delivery; nanomedicines

Phosphorus Chemistry and Life & Health science > 2) Phosphorus chemistry in medicine

Among many types of dendrimers, phosphorus dendrimers or dendrons possessing biocompatible backbone have been employed in multiple therapeutic areas. The major features and advantages of phosphorous dendrimers or dendrons are their rigid backbones and intrinsic bioactivity depending on their terminal functional groups, which are very different from those of poly(amidoamine) dendrimers. In the past five years, we have been extensively working in the development of nanomedicines based on phosphorus dendrimers or dendrons to tackle cancer and inflammatory diseases. In particular, we have shown that cationic phosphorous dendrimers with different generations (G1-3) and surface cyclic amine groups can be optimized for p53-encoding pDNA delivery to take down cancer; stable -P=N-P=S bond-containing bioactive per se amphiphilic phosphorus dendron nanomicelles can be created to load anticancer drug for enhanced chemotherapy of breast cancer; amphiphilic phosphorus dendrons bearing a long linear alkyl chain and ten protonated pyrrolidine surface groups can co-deliver microRNA inhibitor and doxorubicin for augmented triple negative breast cancer therapy. To achieve theranostics of cancer, drug-free phosphorus dendrimer-copper(II) complexes (1G3-Cu) have been developed to enhanced tumor magnetic resonance (MR) imaging and chemotherapy through ultrasound-enabled improved tumor accumulation. Furthermore, the 1G3-Cu complexes can also be incorporated within redox-responsive polymer nanoparticles simultaneously loaded with toyocamycin drug to potentiate MR imaging-guided enhanced tumor immunotherapy via amplification of endoplasmic reticulum stress and mitochondrial dysfunction. Lastly, for anti-inflammatory disease treatment, we have shown that tyramine-bearing two dimethylphosphonate sodium salt (TBP)-modified amphiphilic phosphorus dendron (C11G3) nanomicelles can be encapsulated with antioxidant drug curcumin for combination anti-inflammatory and antioxidative therapy of acute lung injury by virtue of the intrinsic anti-inflammatory activity of the dendrons. Meanwhile, cationic phosphorus dendron nanomicelles can also be used as a vector to co-deliver microRNA mimic and microRNA inhibitor to enhance the anti-inflammatory therapy of acute lung injury.