The interaction of a model protein, bovine serum albumin (BSA) with two different metal oxide nanoparticles, TiO (∼22nm) and SiO (∼14nm), was studied at both physiological and acidic pH. The pH- and nanoparticle-dependent differences in protein structure and protein adsorption were determined using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and thermogravimetric analysis (TGA). The results indicated that the surface coverage of BSA decreases with decreasing pH on both TiO and SiO surfaces, and BSA coverage is higher by a factor of ca. 3-10times more on TiO compared to SiO. The secondary structure of BSA changes upon adsorption to either nanoparticle surface at both pH 7.4 and 2. At acidic pH, BSA appears to completely unfold on TiO nanoparticles whereas it assumes an extended conformation on SiO. These differences highlight for the first time the extent to which the protein corona structure is significantly impacted by protein-nanoparticle interactions which depend on the interplay between pH and specific nanoparticle surface chemistry.

The recent progress in harnessing the efficient and precise method of DNA editing provided by CRISPR/Cas9 is one of the most promising major advances in the field of gene therapy. However, the development of safe and optimally efficient delivery systems for CRISPR/Cas9 elements capable of achieving specific targeting of gene therapy to the location of interest without off-target effects is a primary challenge for clinical therapeutics. Nanoparticles (NPs) provide a promising means to meet such challenges. In this review, we present the most recent advances in developing innovative NP-based delivery systems that efficiently deliver CRISPR-Cas9 constructs and maximize their effectiveness.

Bovine serum albumin (BSA) adsorbed on amorphous silicon dioxide (SiO2) nanoparticles was studied as a function of pH across the range of 2 to 8. Aggregation, surface charge, surface coverage, and protein structure were investigated over this entire pH range. SiO2 nanoparticle aggregation is found to depend upon pH and differs in the presence of adsorbed BSA. For SiO2 nanoparticles truncated with hydroxyl groups, the largest aggregates were observed at pH 3, close to the isoelectric point of SiO2 nanoparticles, whereas for SiO2 nanoparticles with adsorbed BSA, the aggregate size was the greatest at pH 3.7, close to the isoelectric point of the BSA-SiO2 complex. Surface coverage of BSA was also the greatest at the isoelectric point of the BSA-SiO2 complex with a value of ca. 3 ± 1 × 1011 molecules cm−2. Furthermore, the secondary protein structure was modified when compared to the solution phase at all pH values, but the most significant differences were seen at pH 7.4 and below. It is concluded that protein–nanoparticle interactions vary with solution pH, which may have implications for nanoparticles in different biological fluids (e.g., blood, stomach, and lungs).