Figure 9. . Hypothesized cellular uptake of metallic Isonanotubes-M-siRNA and semiconducting Isonanotubes-S-siRNA complexes, the release of siRNA inside the cell and its nuclear translocation based on consideration of experimental data.

(A) Endocytosis-dependent and (B) endocytosis-independent pathways have been postulated as possible uptake mechanisms. After internalization via pathway A or B, the endosomal or cytosolic environment favors the dissociation of siRNA from IsoM, but not IsoS, due to the weak noncovalent interaction between siRNA and IsoM single wall carbon nanotubes. IsoS nanotubes are wrapped more tightly by siRNA and it may not dissociate from IsoS nanotubes inside the cell after either endosomal escape or nonendocytotic uptake. The IsoM-siRNA complex is taken up by a nonendocytotic process and the released siRNA from IsoM after endosomal escape could translocate to the nucleus. Contrary to the IsoM complex, the delivery of IsoS-siRNA complex into the nucleus is inhibited in intact cells, possibly through an unknown cytoplasmic pathway which is not present in purified nuclei. In the absence of specific labeling of the nanotubes themselves, the nuclear translocation of free IsoM nanotubes is uncertain and will need further examination.

IsoM: Isonanotubes metallic; IsoS: Isonanotubes semiconducting.