Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery

Abstract

The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristics—quick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds’ escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds’ cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier.

Optical imaging of localized chemical events using programmable diamond quantum nanosensors

“…These NDs hold great promise for a range of biomedical applications, including serving as nanomedicine platforms for delivery of drugs18, genes and proteins1920, use as fluorescent/photoacoustic imaging agents132122 and applications in multifunctional intracellular sensing232425. The fluorescence of these atomic-scale NV centres in NDs depends on their electronic spin states, which show a long coherence time even under ambient conditions, enabling direct nanoscale sensing for magnetic/electric field1526, temperature242728 and mechanical force/pressure2930.…”

Versatile Multicolor Nanodiamond Probes for Intracellular Imaging and Targeted Labeling

“…Figure 3 shown for other cell lines that the FNDs are usually trapped in endosomes for an hour prior to translocation to the cytoplasm following degradation of the vesicles. [26] This did not appear to be the case here, as the FNDs appear to accumulate in cellular vesicles. As the time increases .…”

“…Previous studies by others have demonstrated that internalization of FNDs occurs through endocytosis, specifically via macropinocytosis. [26] This is the most likely uptake for the SiV containing FNDs while FNDs hosting NV color centers would be internalized via a different non-receptor mediated process as their surface is conjugated with the TAT peptide ( Figure 3 (e-h)). It can be seen that SiV FNDs appear to spread over the entire cell cytoplasm ( Figure 3(a-d)), while NV FNDs with TAT peptide localized to discrete areas ( Figure 3 (e-h)).…”

Nanodiamond: A high impact nanomaterial

“…In general, most sub-10 nm particles exhibit a rounded shape, but the sharp facets of HPHT diamond is more pronounced in >10-20 nm particles. The sharp faces of HPHT have potential for gene therapy, where cell penetration is fast and accompanied by low cytotoxicity [53]. It would be ideal to produce uniformly shaped HPHT nanodiamond without the sharp facets, since the nitrogen content ($100 to 200 ppm) is substantially lower than that of DND ($10,000 ppm), and it is therefore best suited for florescent imaging applications.…”