The aim of this study was to determine the size-dependent penetration ability of gold nanoparticles and the potential application of ultrasmall gold nanoparticles for intranucleus delivery and therapy. We synthesized gold nanoparticles with diameters of 2, 6, 10, and 16 nm and compared their intracellular distribution in MCF-7 breast cancer cells. Nanoparticles smaller than 10 nm (2 and 6 nm) could enter the nucleus, whereas larger ones (10 and 16 nm) were found only in the cytoplasm. We then investigated the possibility of using ultrasmall 2 nm nanoparticles as carriers for nuclear delivery of a triplex-forming oligonucleotide (TFO) that binds to the c-myc promoter. Compared to free TFO, the nanoparticle-conjugated TFO was more effective at reducing c-myc RNA and c-myc protein, which resulted in reduced cell viability. Our result demonstrated that the entry of gold nanoparticles into the cell nucleus is critically dependent on the size of the nanoparticles. We developed a strategy for regulating gene expression, by directly delivering TFOs into the nucleus using ultrasmall gold nanoparticles. More importantly, guidelines were provided to choose appropriate nanocarriers for different biomedical purposes.

Tetraphenylethene and doxorubicin are assembled into a self-indicating drug delivery system (TD NPs). TD NPs are decomposed into DOX and TPE NPs in lysosome. Since TD NPs, TPE NPs and DOX are all fluorescent, the detachment of DOX from TPE NPs is accompanied by fluorescence changing. By observing the fluorescence changes, the spatiotemporal drug release is visualized.

Poor penetration of therapeutic drugs into tumors is a major challenge in anticancer therapy, especially in solid tumors, leading to reduced therapeutic efficacy in vivo. In the study, we used a new tumor-penetrating peptide, CRGDK, to conjugate onto the surface of doxorubicin encapsulated nanoscale micelles. The CRGDK peptide triggered specific binding to neuropilin-1, leading to enhanced cellular uptake and cytotoxicity in vitro and highly accumulation and penetration in the tumors in vivo.