Herein, we demonstrate that the surface charge of gold nanoparticles (AuNPs) plays a critical role in modulating membrane potential of different malignant and nonmalignant cell types and subsequent downstream intracellular events. The findings presented here describe a novel mechanism for cell-nanoparticle interactions and AuNP uptake: modulation of membrane potential and its effect on intracellular events. These studies will help understand the biology of cell-nanoparticle interactions and facilitate the engineering of nanoparticles for specific intracellular targets.
There is a direct correlation between protein levels and disease states in human serum making it an attractive target for sensors and diagnostics. However this is made challenging because serum features more than 20,000 proteins with an overall protein content of greater than 1 mM. Here we report a hybrid synthetic-biomolecule based sensor that uses green fluorescent protein-nanoparticle arrays to detect proteins at biorelevant concentrations in both buffer and human serum. Distinct and reproducible fluorescence response patterns were obtained from five serum proteins (human serum albumin, immunoglobulin G, transferrin, fibrinogen and α-antitrypsin) in buffer and when spiked into human serum. Using linear discriminant analysis we identified these proteins with an identification accuracy of 100% in buffer and 97% in human serum. The arrays were also able to discriminate between different concentrations of the same protein as well as a mixture of different proteins in human serum.
Importance of the field-Site-specific drug delivery is an important area of research that is anticipated to increase the efficacy of the drug and reduce potential side effects. Due to this, substantial work has been done developing non-invasive and targeted tumor treatment with nanoscale metallic particles.Areas covered in this review-This review focuses on the work done in the last several years developing gold nanoparticles as cancer therapeutics and diagnostic agents. However, there are challenges in using gold nanoparticles as drug delivery systems such as biodistribution, pharmacokinetics, and possible toxicity. Approaches to limit these issues are proposed.What the reader will gain-Different approaches from several different disciplines are discussed. Potential clinical applications of these engineered nanoparticles is also presented.Take home message-Because of their unique size-dependent physico-chemical and optical properties, adaptability, sub-cellular size, and bio-compatibility, these nanosized carriers offer an apt means of transporting small molecules as well as biomacromoleculs to diseased cells/ tissues.
BackgroundInorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution.Method/Principal FindingsUsing a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum.ConclusionNeutral and zwitterionic nanoparticles demonstrated longer circulation time via both IP and IV administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting.
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