Protein Corona-Enabled Systemic Delivery and Targeting of Nanoparticles.

Upon systemic administration, nanoparticles encounter serum proteins in the biological system resulting in the formation of "protein corona" on the surface. Increased understanding of the relationship between nanoparticles' "chemical identity" and "biological identity" can contribute to improved clinical translation. Recent studies of protein corona composition on nanoparticles, including from our group, suggest that a strategic choice of materials can influence the types of protein adsorbed from plasma and lead to improved delivery efficiency. This mini-review reflects on the fundamental knowledge of nanoparticle protein corona and highlights the recent applications of protein corona on nanoparticles' systemic circulation, cell, and tissue-specific delivery. Important considerations on the safety and efficacy aspects pertaining to the exploration of nanoparticle protein corona's targeting effect are also summarized. Finally, the future perspectives of protein corona research are discussed.

Cold Atmospheric Plasma Induces ATP-Dependent Endocytosis of Nanoparticles and Synergistic U373MG Cancer Cell Death.

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are significantly increased when exposed to 75 kV CAP generated by dielectric barrier discharge. No significant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological effects of CAP, long-lived reactive species were not involved, and plasma-activated liquids did not replicate the effect. Chemical effects induced by direct and indirect exposure to CAP appears the dominant mediator of enhanced uptake. Transient physical alterations of membrane integrity played a minor role. 3D-reconstruction of deconvoluted confocal images confirmed AuNP accumulation in lysosomes and other acidic vesicles, which will be useful for future drug delivery and diagnostic strategies. Toxicity of AuNP significantly increased by 25-fold when combined with CAP. Our data indicate that direct exposure to CAP activates AuNP-dependent cytotoxicity by increasing AuNP endocytosis and trafficking to lysosomes in U373MG cells.