Abstract
Nanomedicine is seen as a potential central player in the delivery of personalized medicine. Biocompatibility issues of nanoparticles have largely been resolved over the past decade. Despite their tremendous progress, less than 1% of applied nanosystems can hit their intended target location, such as a solid tumor, and this remains an obstacle to their full ability and potential with a high translational value. Therefore, achieving immune-tolerable, blood-compatible, and biofriendly nanoparticles remains an unmet need. The translational success of nanoformulations from bench to bedside involves a thorough assessment of their design, compatibility beyond cytotoxicity such as immune toxicity, blood compatibility, and immune-mediated destruction/rejection/clearance profile. Here, we report a one-pot process-engineered synthesis of ultrasmall gold nanoparticles (uGNPs) suitable for better body and renal clearance delivery of their payloads. We have obtained uGNP sizes of as low as 3 nm and have engineered the synthesis to allow them to be accurately sized (almost nanometer by nanometer). The synthesized uGNPs are biocompatible and can easily be functionalized to carry drugs, peptides, antibodies, and other therapeutic molecules. We have performed in vitro cell viability assays, immunotoxicity assays, inflammatory cytokine analysis, a complement activation study, and blood coagulation studies with the uGNPs to confirm their safety. These can help to set up a long-term safety-benefit framework of experimentation to reveal whether any designed nanoparticles are immune-tolerable and can be used as payload carriers for next-generation vaccines, chemotherapeutic drugs, and theranostic agents with better body clearance ability and deep tissue penetration.
Highlights
Nanotechnology has had a huge influence in the field of biomedicine, such as in therapy, diagnosis, vaccination, and biosensing.[1]
In an effort to better understand the reaction mechanism and study the factors affecting the size of particles, the role of tannic acid (TA) and NaCit as reducing agents on the reaction rate and the final particle size of ultrasmall gold nanoparticles (uGNPs) was thoroughly investigated
The results indicate that uGNPs in human blood plasma are blood-compatible, and this observation further validates that the as-synthesized particles can prove to be an exceptionally valuable asset for nanomedicine translational studies
Summary
Nanotechnology has had a huge influence in the field of biomedicine, such as in therapy, diagnosis, vaccination, and biosensing.[1]. Nanoparticles with a smaller core and larger PEG coatings confer a longer blood circulation time than a similar size but composed of a bigger core and thinner coatings.[34] Glutathione-coated gold nanoparticles (GNPs) undergo faster renal clearance than those coated with BSA and heavily accumulate in the liver and spleen in mice.[35] a small core is a prerequisite for rendering small particles It appears that smaller particles should be beneficial in biomedical applications, an optimal particle size is believed to be application-specific.[34] the abilities to fabricate ultrasmall nanoparticles and to finely tune their size are both highly desirable. While the synthetic platform was extremely valuable for making immune-safe and precisely tunable nanoparticles to meet the specific size requirements in any biomedical applications, the framework of testing their immune compatibility can be beneficial to a wider collection of nanomaterials for biomedical applications
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