Dendrimer-Modified Carbon Nanoparticles with Excitation-Independent Long Wavelength Emission for siRNA Delivery

Inspired by the distinctive merits of carbon nanoparticles (CNPs) and poly(amidoamine) (PAMAM) dendrimers, we synthesized PAMAM modified CNPs (CNPs-PAMAM). First, CNPs were prepared using citrate acid and 1, 2, 4-triaminobenzene. Then, PAMAM was anchored on the surface of CNPs. The structure of PAMAM would remain unchanged under mild conditions of the postmodification method, making PAMAM retain its excellent drug carrying ability. Particularly, CNPs-PAMAM had exceptional optical properties of excitation-independent long wavelength emission. Excitation-independent emission can ensure the sensitivity of bioimaging. Long wavelength emission can avoid the autofluorescence interference of biological matrixes and have good tissue penetration. Further studies demonstrated that CNPs-PAMAM were able to electrostatically bind and condense small interfering RNA (siRNA) into stabilized nanocomplexes. The siRNA complexed with CNPs-PAMAM was endowed with an increased resistance against degradation and an enhanced cellular uptake. Moreover, CNPs-PAMAM-complexed siRNA targeting histone deacetylase 2 (HDAC2) could be effectively delivered into the neuron-like PC-12 cells, and exert its gene-silencing effect. Precisely inhibiting the so-called undruggable target HDAC2 opens a novel strategy for ischemic stroke treatment. Thus, CNPs-PAMAM offer a promising delivery carrier to unleash the siRNA’s therapeutic potential.