Structural and Property Characterizations of Dual-Responsive Core-Shell Tecto Dendrimers for Tumor Penetration and Gene Delivery Applications

Core-shell tecto dendrimers (CSTDs) with excellent physicochemical properties and good tumor penetration and gene transfection efficiency have been demonstrated to have the potential to replace high-generation dendrimers in biomedical applications. However, their characterization and related biological properties of CSTDs for enhanced tumor penetration and gene delivery still lack in-depth investigation. Herein, three types of dual-responsive CSTDs are designed for thorough physicochemical characterization and investigation of their tumor penetration and gene delivery efficiency. Three types of CSTDs are prepared through phenylborate ester bonds of phenylboronic acid (PBA)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and monose (galactose, glucose, or mannose)-conjugated G3 PAMAM dendrimers as shells and thoroughly characterized via NMR and other techniques. It is shown that the produced CSTDs display strong correlation signals between the PBA and monose protons, similar hydrodynamic diameters, and dual reactive oxygen species- and pH-responsivenesses. The dual-responsive CSTDs are proven to have structure-dependent tumor penetration property and gene delivery efficiency in terms of small interference RNA for gene silencing and plasmid DNA for gene editing, thus revealing a great potential for different biomedical applications. Core-shell tecto dendrimers with dual responsivenesses have been designed through phenylborate ester bonds between phenylboronic acid-decorated generation 5 poly(amidoamine) dendrimers as cores and monose-conjugated generation 3 dendrimers as shells. The materials are thoroughly characterized by NMR and other technologies, and applied for tumor penetration and gene delivery of small interfering RNA and plasmid DNA with desired performances. image