Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications

http://experimentationlab.berkeley.edu/sites/default/files/AFMImages/butt_AFM.pdf

Force measurements with the atomic force microscope: Technique, interpretation and applications

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

/pdf/advances-and-challenges-of-liposome-assisted-drug-delivery-icfpw75u2e.pdf

Advances and Challenges of Liposome Assisted Drug Delivery.

Light-powered molecular machines are conjectured to be essential constituents of future nanoscale devices As a model for such systems, we have synthesized a polymer of bistable photosensitive azobenzenes Individual polymers were investigated by single-molecule force spectroscopy in combination with optical excitation in total internal reflection We were able to optically lengthen and contract individual polymers by switching the azo groups between their trans and cis configurations The polymer was found to contract against an external force acting along the polymer backbone, thus delivering mechanical work As a proof of principle, the polymer was operated in a periodic mode, demonstrating for the first time optomechanical energy conversion in a single-molecule device

https://science.sciencemag.org/content/sci/296/5570/1103.full.pdf

Single-Molecule Optomechanical Cycle

The external region of a cell membrane, known as the glycocalyx, is dominated by glycosylated molecules1,2,3 which direct specific interactions such as cell–cell recognition and contribute to the steric repulsion that prevents undesirable non-specific adhesion of other molecules and cells. Mimicking the non-adhesive properties of a glycocalyx provides a potential solution to the clinical problems, such as thrombosis4, that are associated with implantable devices owing to non-specific adsorption of plasma proteins. Here we describe a biomimetic surface modification of graphite using oligosaccharide surfactant polymers, which, like a glycocalyx, provides a dense and confluent layer of oligosaccharides. The surfactant polymers consist of a flexible poly(vinyl amine) with dextran and alkanoyl side chains. We show that alkanoyl side chains assemble on graphite through hydrophobic interaction and epitaxial adsorption. This constrains the polymer backbone to lie parallel to the substrate, with solvated dextran side chains protruding into the aqueous phase, creating a glycocalyx-like coating. The resulting biomimetic surface is effective in suppressing protein adsorption from human plasma protein solution.

Biomimetic engineering of non-adhesive glycocalyx-like surfaces using oligosaccharide surfactant polymers

The reversible, optical switching of individual polymer molecules was observed using molecular force spectroscopy. We synthesized a polypeptide with multiple photoactive azobenzene groups incorporated in the backbone. The contour length of the polymer could be selectively lengthened or shortened by switching between the trans- and cis-azo configurations with 420 and 365 nm wavelength light, respectively. This cis- to trans-azo configurational transition induced by ultraviolet light resulted in a measurable change in polymer contour length. The contour length change was observed at low force and under external loads of up to 400 pN using a modified force spectrometer, in which the sample could be irradiated in total internal reflectance. The ability to shorten the polymer against an external load is the first demonstration of photomechanical energy conversion in an individual molecule. This is a significant milestone in the road toward molecular level machines.

Single Molecule Force Spectroscopy of Azobenzene Polymers: Switching Elasticity of Single Photochromic Macromolecules

Theranostics is a promising field that combines therapeutics and diagnostics into single multifunctional formulations. This field is driven by advancements in nanoparticle systems capable of providing the necessary functionalities. By utilizing these powerful nanomedicines, the concept of personalized medicine can be realized by tailoring treatment strategies to the individual. This review gives a brief overview of the components of a theranostic system and the challenges that designing truly multifunctional nanoparticles present. Considerations when choosing a class of nanoparticle include the size, shape, charge, and surface chemistry, while classes of nanoparticles discussed are polymers, liposomes, dendrimers, and polymeric micelles. Targeting to disease states can be achieved either through passive or active targeting which uses specific ligands to target receptors that are overexpressed in tumors and common targeting elements are presented. To image the interactions with disease states, contrast agents are included in the nanoparticle formulation. Imaging options include optical imaging techniques, computed tomography, nuclear based, and magnetic resonance imaging. The interplay between all of these components needs to be carefully considered when designing a theranostic system.

Multifunctional nanoparticles for use in theranostic applications.

In the past several years, atomic force microscopy (AFM) has provided topographic images of adsorbed plasma proteins in situ at unprecedented resolution. Imaging has been limited to adsorbed protein on relatively smooth model substrates such as mica, graphite, or self-assembled monolayers on which the small height of the protein can be observed from the background. The inherent roughness of biomaterial surfaces has prevented observation of adsorbed proteins in topographic images. We report imaging isolated fibrinogen molecules adsorbed on National Heart Lung and Blood Institute (NHLBI) reference materials polydimethylsiloxane and low-density polyethylene in situ using phase imaging AFM. Fibrinogen, a plasma protein important for blood coagulation and platelet aggregation, was adsorbed from dilute solution onto reference biomaterial surfaces at sub-monolayer coverage. Tapping mode AFM was used to image the samples. For polydimethylsiloxane, the lateral size of the surface features is much greater than the dimensions of proteins. This allowed adsorbed proteins to be observed in topographic images. The phase imaging signal of tapping mode AFM provides information on differences in material properties of the surface, and was used to distinguish individual protein molecules from the underlying polymer surface. On the low-density polyethylene surface, characteristic topographical features are of the same magnitude as the protein molecules, so that protein cannot be distinguished from the surface using topographic images. However, phase images were used to successfully locate and characterize the distribution of the protein. Phase imaging was not able to distinguish fibrinogen adsorbed onto expanded polytetrafluoroethylene. The utility and limitations of the phase imaging technique for characterizing protein adsorption to rough surfaces is discussed.

Nolan B. Holland

Papers

Single-Molecule Optomechanical Cycle

Biomimetic engineering of non-adhesive glycocalyx-like surfaces using oligosaccharide surfactant polymers

Single Molecule Force Spectroscopy of Azobenzene Polymers: Switching Elasticity of Single Photochromic Macromolecules

Multifunctional nanoparticles for use in theranostic applications.

Individual plasma proteins detected on rough biomaterials by phase imaging AFM.