Synthesis and Characterization of Hybrid Polymer/Lipid Expansile Nanoparticles: Imparting Surface Functionality for Targeting and Stability.

The size, drug loading, drug release kinetics, localization, biodistribution, and stability of a given polymeric nanoparticle (NP) system depend on the composition of the NP core as well as its surface properties. In this study, novel, pH-responsive, and lipid-coated NPs, which expand in size from a diameter of approximately 100 to 1000 nm in the presence of a mildly acidic pH environment, are synthesized and characterized. Specifically, a combined miniemulsion and free-radical polymerization method is used to prepare the NPs in the presence of PEGylated lipids. These PEGylated-lipid expansile NPs (PEG-L-eNPs) combine the swelling behavior of the polymeric core of expansile NPs with the improved colloidal stability and surface functionality of PEGylated liposomes. The surface functionality of PEG-L-eNPs allows for the incorporation of folic acid (FA) and folate receptor-targeting. The resulting hybrid polymer/lipid nanocarriers, FA-PEG-L-eNPs, exhibit greater in vitro uptake and potency when loaded with paclitaxel compared to nontargeted PEG-L-eNPs.

Shape-dependent antibacterial effects of non-cytotoxic gold nanoparticles.

Gold nanoparticles (AuNPs) of various shapes (including spheres, stars and flowers), with similar dimensions, were synthesized and evaluated for their antibacterial effects toward Staphylococcus aureus, a bacterium responsible for numerous life-threatening infections worldwide. Optical growth curve measurements and Gompertz modeling showed significant AuNP shape- and concentration-dependent decreases in bacterial growth with increases in bacterial growth lag time. To evaluate prospective use in in vivo systems, the cytotoxicity of the same AuNPs was evaluated toward human dermal fibroblasts in vitro by 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) viability assays and confocal microscopy. No indication of any mammalian cell toxicity or morphological effects was found. Additionally, it was observed that the AuNPs were readily internalized in fibroblasts after 4 days of incubation. Most importantly, the results of the present study showed that gold nanoflowers in particular possessed the most promising non-cytotoxic mammalian cell behavior with the greatest shape-dependent antibacterial activity-promising properties for their future investigation in a wide range of anti-infection applications.

Decreased bacterial growth on titanium nanoscale topographies created by ion beam assisted evaporation.

Titanium is one of the most widely used materials for orthopedic implants, yet it has exhibited significant complications in the short and long term, largely resulting from poor cell-material interactions. Among these many modes of failure, bacterial infection at the site of implantation has become a greater concern with the rise of antibiotic-resistant bacteria. Nanostructured surfaces have been found to prevent bacterial colonization on many surfaces, including nanotextured titanium. In many cases, specific nanoscale roughness values and resulting surface energies have been considered to be "bactericidal"; here, we explore the use of ion beam evaporation as a novel technique to create nanoscale topographical features that can reduce bacterial density. Specifically, we investigated the relationship between the roughness and titanium nanofeature shapes and sizes, in which smaller, more regularly spaced nanofeatures (specifically 40-50 nm tall peaks spaced ~0.25 µm apart) were found to have more effect than surfaces with high roughness values alone.

Emerging Trends in Micro- and Nanoscale Technologies in Medicine: From Basic Discoveries to Translation.

We discuss the state of the art and innovative micro- and nanoscale technologies that are finding niches and opening up new opportunities in medicine, particularly in diagnostic and therapeutic applications. We take the design of point-of-care applications and the capture of circulating tumor cells as illustrative examples of the integration of micro- and nanotechnologies into solutions of diagnostic challenges. We describe several novel nanotechnologies that enable imaging cellular structures and molecular events. In therapeutics, we describe the utilization of micro- and nanotechnologies in applications including drug delivery, tissue engineering, and pharmaceutical development/testing. In addition, we discuss relevant challenges that micro- and nanotechnologies face in achieving cost-effective and widespread clinical implementation as well as forecasted applications of micro- and nanotechnologies in medicine.

Reducing bone cancer cell functions using selenium nanocomposites.

Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation, and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, noncancerous, osteoblast functions (for example, up to two times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of this study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects.