BioAcyl Corp

Silica NPs are one of the commonly used NO donors for local delivery of NO. The simple and easy mode of synthesis, tunable surface chemistry and size, sustained release, and non-toxic properties make silica NPs a potent potential NO delivery carrier.[192] Silica NPs as small as 30 nm in diameter were synthesized via amino silane template surfactant ion exchange reaction and demonstrated the capability to enhance the payload of NO inside the NPs and trigger their sustained release.[193] NO-releasing silica NPs can induce a significant bactericidal action that is tunable according to shape, particle size, and surface properties.[194] NO-releasing silica nanospheres with diameters within the range of 14–50 nm were more potent against both gram-positive and gram-negative bacteria compared to larger ones.[194] In another study, a higher aspect ratio of silica NPs with smaller sizes was also shown to contribute to anti-bacterial activities.[195] The NO-releasing characteristics of silica NPs can be tuned via surface modifications. In a similar study, the authors demonstrated the surface modification of silica NPs with PEG, reduced the half-life of the donors through their decomposition, which occurred due to the large water absorption capacity of PEG, resulting in faster degradation of the delivery vehicle. This type of NPs exhibited enhanced antibacterial properties because of an increase in NO flux in the biological environment.[194] Other than silica NPs, gold (Au) NPs represent another promising option as NO donors.[196] The unique physiochemical properties of AuNPs enable efficient transport and release of desired drugs, making them highly versatile for loading and continuous release of NO.[178, 197] The synthesis of AuNPs is straightforward, and their inert and non-toxic core allows for safe utilization. Furthermore, AuNPs can be functionalized in a tunable manner, adding to their versatility in drug delivery. They can respond to various internal or external stimuli such as pH, GSH, and light, triggering the release of NO.[178] The presence of AuNPs facilitates the formation of S–Au bonds, which have lower dissociation energy compared to S–N bonds, resulting in the release of NO.[198] Studies have demonstrated that increasing the concentration of AuNPs enhances NO generation due to the larger surface area available.[198] Surface grafting of AuNPs using block copolymers can achieve slow and controlled NO release, exhibiting significant antibiofilm activity.[197] Additionally, the development of a NIR-triggered NO nanogenerator (SNP@MOF@Au-Mal) demonstrated a synergistic antibacterial effect against P. aeruginosa infection when exposed to NIR irradiation.[185] Despite the continuous advancements in the development of AuNPs for therapeutic applications, challenges persist that limit their translational potential.