Impact of macroporous silica nanoparticles at sub-50nm on bio-behaviors and biosafety in drug-resistant cancer models

The in vivo bio-behaviors and biosafety of nanoparticles were demonstrated to be closely correlated with particle sizes, which illustrated whether they could be used as the effective drug delivery carriers. Though tumor penetration capabilities of the small pore sized-mesoporous silica nanoparticles (MSNs) were reported to be in a particle size-dependent manner, the size effects of large pore sized-MSNs on the safe and effective cancer resistance treatment, especially at sub-50 nm, were not explicitly evaluated. In this study, we fabricate the 20 nm and 50 nm MSNs, and aim at investigating their difference in tumor accumulation, penetration, retention and toxicity both in vitro and in vivo. Our results showed that these two particle sized-MSNs possessed the excellent tumor penetration capabilities both in resistant human hepatocellular carcinoma cells-cultured spheroids and in the corresponding xenograft mice models, but the 50 nm MSNs seemed to have the better tumor accumulation and retention effects than the 20 nm MSNs. Moreover, the 50 nm MSNs displayed the lower toxicities than the 20 nm MSNs whatever on resistant cancer cell lines or on zebrafish embryos, indicating the greater systematic biosafety. In a word, our data provide the evidence that selection of the large pore-sized MSNs at the appropriate particle size (not the smaller the better) as bio-macromolecule nanocarriers will play a key role in the safe and effective treatment against cancer resistance.