Shape Effect of Carbon Nanovectors on Angiogenesis

Abstract

Physically diverse carbon nanostructures are increasingly being studied for potential applications in cancer chemotherapy. However, limited knowledge exists on the effect of their shape in tuning the biological outcomes when used as nanovectors for drug delivery. In this study, we evaluated the effect of doxorubicin-conjugated single walled carbon nanotubes (CNT-Dox) and doxorubicin-conjugated spherical polyhydroxylated fullerenes or fullerenols (Ful-Dox) on angiogenesis. We report that CNTs exert a pro-angiogenic effect in vitro and in vivo. In contrast, the fullerenols or doxorubicin-conjugated fullerenols exerted a dramatically opposite antiangiogenic activity in zebrafish and murine tumor angiogenesis models. Dissecting the angiogenic phenotype into discrete cellular steps revealed that fullerenols inhibited endothelial cell proliferation, while CNTs attenuated the cytotoxic effect of doxorubicin on the endothelial cells. Interestingly, CNT promoted endothelial tubulogenesis, a late step during angiogenesis. Further, mechanistic studies revealed that CNTs, but not fullerenols, induced integrin clustering and activated focal adhesion kinase and downstream phosphoinositide-3-kinase (PI3K) signaling in endothelial cells, which can explain the distinct angiogenic outcomes. The results of the study highlight the function of physical parameters of nanoparticles in determining their activity in biological settings.

Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

“…28 In anticancer therapy, allotropic forms of carbon are also applied as a drug delivery system. Conjugate water-soluble single-walled nanotube-palitaxel 29 and single-walled nanotube-doxorubicin 30 enhance permeability and retention in xenograft tumors, while not changing the effect of the medical treatment. Murugesan et al 31 proved the antiangiogenic properties of graphite nanoparticles, multi-walled carbon nanotubes, and C60 fullerenes on the blood vessels of chicken chorioallantoic membrane.…”

Biological applications of hydrophilic C60 derivatives (hC60s)− a structural perspective

“…Moreover, PEG-C60(OH)16-24-DOX completely inhibited angiogenesis at the concentration of 100 µM (calculated by DOX) and DOX alone did not show any inhibition. In other model to detect endothelial tubulogenesis, PEG-C60(OH)16-24-DOX strengthened the tubulogenesis inhibition of either C60(OH) [16][17][18][19][20][21][22][23][24] or DOX at the concentration of 1 µM and it did not bear the cytotoxicity [38].…”

“…C60(OH)16-24 not only lowered DOX toxicity towards heart, but also inhibited angiogenesis, which assisted DOX to inhibit tumor cells [37,38]. PEG-C60(OH)16-24-DOX inhibited the growth of mouse melanoma cell line B16−F10.…”

Nanotechnology Based Targeted Drug Delivery: Current Status and Future Prospects for Drug Development

“…It has been shown that polymer-conjugated angiogenesis inhibitor TNP-470 (caplostatin) accumulates selectively in the tumor vessels by the EPR effect and inhibits hyperpermeability of tumor blood vessels (Satchi-Fainero et al, 2005;Satchi-Fainero et al, 2004). Nanoparticle-conjugated chemotherapeutic agents such as doxorubicin (Chaudhuri et al, 2010) and angiogenic small molecule inhibitors ) can preferentially home into tumors by the EPR effect, resulting in selective vascular shutdown and inhibition of tumor growth. It should be noted that EPR alone is not always sufficient in targeting the tumor sites and hence is often used in conjunction with active targeting.…”