Biodegradable Plasmon Resonant Nanoshells

Abstract

Demonstration of biocompatible quantum dots ten years ago [1,2] spurred interest in various nanomaterials with fascinating optical, electronic and magnetic properties, and their potential for medical applications. [3] Plasmon resonance, an optical phenomenon associated with metal nanoparticles, is currently investigated for biomedical imaging and intervention at the cellular level (Table 1). However, requirements of complete elimination from the body may limit the clinical utility of nanoparticles of these sizes. [18] Here we report preparation and testing of biodegradable plasmon resonant nanoshells of 63 nm diameter. Rather than a continuous metallic shell, this composite nanostructure is formed as a shell-shaped array of gold clusters supported on a spherical biodegradable core. This fundamentally new class of materials maintains optical tunability characteristic of solid metallic shells, yet upon degradation yields individual clusters of 5.7 nm diameter, compatible with the requirements of renal clearance. Biodegradable metallic nanoparticles may enable clinical translation of many research-stage technologies.In the Rayleigh approximation of small non-interacting spherical particles, plasmon resonance occurs when ε= −2ε m where ε is the dielectric function of the particles and ε m is that of the medium, and results in intense absorption and scattering of electromagnetic radiation. [19] Gold is of particular interest to biomedical applications because, in addition to being bioinert, its refractive index satisfies the plasmon resonance condition in the visible range, around 530 nm. With a departure from restrictions of the Rayleigh approximation, particle shape and size further control the spectral position of the plasmon resonance, leading to the optical tunability of such particles throughout the visible to near-infrared range, with opportunities for imaging and therapeutic applications. However, concerns regarding unknown toxicities and elimination routes of nanoparticles [20] led to investigation of the hydrodynamic diameter as a critical parameter in design of diagnostic and therapeutic nanoparticles. Consequently proposed criteria of nanoparticles' clinical utility include "degradability to clearable components", i.e., to particles having hydrodynamic diameter of 5-6 nm or less, clearable by renal filtration. [18] Currently investigated plasmon resonant nanostructures do not meet these criteria (Table 1).In response to this challenge we demonstrate preparation of plasmon resonant nanoshells comprised of an array of gold clusters that upon degradation yield components of a clearable size ( Figure 1a) The optical properties of this composite shell are no longer that of solid

Gold Nanomaterials at Work in Biomedicine

“…These studies clearly demonstrate that Au nanostructures can not only act as carriers for the drugs, but also serve as transducers to trigger the release of drugs in a delivery system. 611 A number of traits have been identified for MDR ( Figure 43A), including increased efflux pumping of drugs by the overexpressed ATP-binding cassette (ABC) transporters, reduced intracellular accumulation of drugs by non-ABC drug transporters, blocked apoptosis, repair of drug-induced DNA damage, metabolic modification, and detoxification by drugmetabolizing enzymes. 613,614,616 Among these, the overexpression of P-glycoprotein, a member of the ABC superfamily, has been recognized as one of the most common causes of MDR.…”

“…611 The important role of Kupffer cells was widely emphasized for the clearance of nanoparticles from the bloodstream, as they are the cells that can actively capture and process particulate materials in the liver. However, Kupffer cells are not actively involved in the process of hepatic clearance of Au nanoparticles from the body because Au can hardly be broken down by the catabolic mechanism and will ultimately accumulate in Kupffer cells.…”

Vibration-assisted optical injection of a single fluorescent sensor into a target cell

“…Before the injection experiment, the surface of the sensor was modified by functional liposome layers. Lipid layers have been used for encapsulation and controlled delivery of soluble drugs [14] and polymer particles [15] into cells for lipofection. Lipofection, as shown in Fig.2, is a technique used to inject biological particles into a cell by means of liposomes, which can easily merge with the cell membrane since they are both made of a phospholipid bilayer.…”

Gold cluster-labeled thermosensitive liposmes enhance triggered drug release in the tumor microenvironment by a photothermal effect

“…Briefly, the composition of lipids Gold coating on the liposomal surface was carried out by plasmon resonance coating methods [26,27]. The gold (III) chloride solution (65 µL of 100 mM) was added to 1 mL of the liposomal solution and was gently stirred.…”