Short Zwitterionic Sulfobetaine-Modified Silica Nanoparticles: Is Neutrality Possible?

Zwitterionic coatings are an efficient strategy for preventing biomolecule adsorption and enhancing nanoparticle stability in solution. The properties of zwitterions and other antifouling materials, including suppression of nonspecific adsorption and improved colloidal stability of nanoparticles, are believed to derive from their electroneutral and highly hydrophilic nature. Among different zwitterions, short sulfobetaines have been demonstrated to be effective in preventing protein adsorption onto several nanoparticles and providing enhanced colloidal stability. Although zwitterionic sulfobetaine silane (ZS) is electrically neutral, the negatively charged zwitterionic sulfobetaine-functionalized silica nanoparticles (ZS@SiO2NPs) exhibit a similar ζ-potential to nonfunctionalized silica nanoparticles (SiO2NPs). In this work, we present a thorough comprehension of the surface properties of ZS@SiO2NPs, which encompasses the development of meticulous functionalization procedures, detailed characterization approaches, and cutting-edge modeling to address the questions that persist regarding the surface features of ZS@SiO2NPs. The negative charge of ZS@SiO2NPs is due to the stabilization of siloxide from residual surface silanols by the quaternary amine in the sulfobetaine structure. Consequently, we infer that zero-charge ZS@SiO2NPs are unlikely to be obtained since this stabilization increases the dissociation degree of surface silanols, increasing the overall structure negative charge. Additionally, colloidal stability was evaluated in different pH and ionic strength conditions, and it was found that ZS@SiO2NPs are more stable at higher ionic strengths. This suggests that the interaction between ZS and salt ions prevents the aggregation of ZS@SiO2NPs. Together, these results shed light on the nature of the ZS@SiO2NP negative charge and possible sources for the remarkable colloidal stability of zwitterionic nanoparticles in complex media.

Protein corona meets freeze-drying: overcoming the challenges of colloidal stability, toxicity, and opsonin adsorption.

Freeze-drying of nanoparticle suspensions is capable of generating stable nanoformulations with improved storage times and easier transportation. Nonetheless, nanoparticle aggregation is likely induced during freeze-drying, which reduces its redispersibility upon reconstitution and leads to undesirable effects such as non-specific toxicity and impaired efficacy. In this work, bovine serum albumin (BSA) is described as a suitable protectant for silica nanoparticles (SNPs), which result in solid structures with excellent redispersibility and negligible signs of aggregation even when longer storage times are considered. We experimentally demonstrated that massive system aggregation can be prevented when a saturated BSA corona around the nanoparticle is formed before the lyophilization process. Furthermore, the BSA corona is able to suppress non-specific interactions between these nanoparticles and biological systems, as evidenced by the lack of residual cytotoxicity, hemolytic activity and opsonin adsorption. Hence, BSA can be seriously considered for industry as an additive for nanoparticle freeze-drying since it generates solid and redispersible nanoformulations with improved biocompatibility.

Tetracycline@silver ions-functionalized mesoporous silica for high bactericidal activity at ultra-low concentration.

Aim: Polyether pores were designed and tetracycline-loaded mesoporous silica materials, with their surface decorated by silver ions, were prepared, with the aim of reaching high antibacterial activity. Meanwhile, mammalian cell cytotoxicity and hemolytic effects were not observed using material concentrations tenfold the ones optimized for the bactericidal tests. Methods: Pore size was tuned by changing the polyether content and the surface was covalently decorated with silver thiolate groups. Results: We showed that the biological activity was enhanced by modulating silver ions and tetracycline releases by tuning silver thiolate group concentration on the silica surface and/or by modulating the pH of the environment. Conclusion: The combined use of tetracycline and silver ions with the mesoporous drug-delivery carrier was a very effective strategy against susceptible and tetracycline-resistant Escherichia coli bacteria.