Aqueous Stable Gold Nanostar/ZIF-8 Nanocomposites for Light-Triggered Release of Active Cargo Inside Living Cells.

A plasmonic core-shell gold nanostar/zeolitic-imidazolate-framework-8 (ZIF-8) nanocomposite was developed for the thermoplasmonic-driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF-8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule-release mechanism relies on the use of near-IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface-enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near-IR-triggered cargo release inside cells, thereby leading to DNA staining.

Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates.

BACKGROUND: We evaluated the frequency of naturally occurring resistance associated substitutions (RASs) and their characteristic of polymorphic or non-polymorphic amino acid change to direct acting antivirals (DAAs) in NS5b HCV subtypes 1a and 1b according to different geographic origin of isolates. METHODS: Using a public database we retrieved 738 worldwide NS5b sequences (for which was available the geographic origin) from HCV genotype (G)1 infected patients naive to DAAs. NS5b sequences clustering with G1a were more conserved in regard of RASs than G1b isolates, (14% vs 57% RASs, P < 0.0001). RESULTS: In G1a, RASs were differently distributed between isolates from Europe (24%) and USA, (12%) P = 0.0186. In particular, 421 V associated with resistance to non-nucleoside inhibitor beclabuvir was polymorphic in Europe and USA, being detected in 24% and 11% of sequences, respectively, P = 0.0140. In G1b, RASs were found in 45% of sequences from Europe, in 54% of isolates from USA and in 70% of sequences from Asia (P = 0.0051). The 316 N polymorphism was detected in 54% of Asian isolates and at lower frequency, in 28% of isolates from USA and in 20% of European sequences (P < 0.0001). CONCLUSIONS: In conclusion, a higher prevalence of RASs in G1b respect to G1a was found and a geographical distribution of RASs and polymorphic aa changes was observed in G1a as well in G1b. The clinical and therapeutic impact of the geographic distribution of RASs to polymerase inhibitors remains to be established, particularly in patients with virologic failure to DAAs and/or advanced liver disease.