Hamidreza Ghandehari

Understanding the toxicity of silica nanoparticles (SiO(2)) on the cellular level is crucial for rational design of these nanomaterials for biomedical applications. Herein, we explore the impacts of geometry, porosity, and surface charge of SiO(2) on cellular toxicity and hemolytic activity. Nonporous Stöber silica nanospheres (115 nm diameter), mesoporous silica nanospheres (120 nm diameter, aspect ratio 1), mesoporous silica nanorods with aspect ratio of 2, 4, and 8 (width by length 80 × 200 nm, 150 × 600 nm, 130 × 1000 nm), and their cationic counterparts were evaluated on macrophages, lung carcinoma cells, and human erythrocytes. It was shown that the toxicity of SiO(2) is cell-type dependent and that surface charge and pore size govern cellular toxicity. Using inductively coupled plasma mass spectrometry, the cellular association of SiO(2) was quantitated with the association amount increasing in the following order: mesoporous SiO(2) (aspect ratio 1, 2, 4, 8) < amine-modified mesoporous SiO(2) (aspect ratio 1, 2, 4, 8) < amine-modified nonporous Stöber SiO(2) < nonporous Stöber SiO(2). Geometry did not seem to influence the extent of SiO(2) association at early or extended time points. The level of cellular association of the nanoparticles was directly linked to the extent of plasma membrane damage, suggesting a biological cause-and-effect relationship. Hemolysis assay showed that the hemolytic activity was porosity- and geometry-dependent for bare SiO(2) and surface-charge-dependent for amine-modified SiO(2). A good correlation between hemolytic activity and cellular association was found on a similar dosage basis. These results can provide useful guidelines for the rational design of SiO(2) in nanomedicine.

The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both "see and treat" patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status.

Using a series of gold nanoparticles with incremental increase in dimensions but varying geometries (spherical vs rods) we have evaluated the influence of shape, size, surface properties and concentration on cellular uptake, adsorption of proteins and toxicity in a human prostate cancer cell line (PC-3). In the range of 30-90 nm diameter studied, spherical particles of 50 nm in diameter without polyethylene glycol (PEG) had the highest uptake. Surface attachment of PEG reduced cellular uptake. PEGylated gold nanorods had a net positive charge compared with their spherical counterparts and particle geometry influenced cellular uptake. In the absence of serum proteins the uptake of plain spherical GNPs increased. These studies pave the way for the tailoring of gold nanoparticles for targeted tumor therapy applications.