Selective Uptake Into Drug Resistant Mammalian Cancer by Cell Penetrating Peptide-Mediated Delivery.

Research over the past decade has identified several of the key limiting features of multidrug resistance (MDR) in cancer therapy applications, such as evolving glycoprotein receptors at the surface of the cell that limit therapeutic uptake, metabolic changes that lead to protection from multidrug resistant mediators which enhance degradation or efflux of therapeutics, and difficulty ensuring retention of intact and functional drugs once endocytosed. Nanoparticles have been demonstrated to be effective delivery vehicles for a plethora of therapeutic agents, and in the case of nucleic acid based agents, they provide protective advantages. Functionalizing cell penetrating peptides, also known as protein transduction domains, onto the surface of fluorescent quantum dots creates a labeled delivery package to investigate the nuances and difficulties of drug transport in MDR cancer cells for potential future clinical applications of diverse nanoparticle-based therapeutic delivery strategies. In this study, eight distinct cell penetrating peptides were used (CAAKA, HSV1-VP22, HIV-TAT, HIV-gp41, Ku-70, hCT(9-32), integrin-ß3, and K-FGF) to examine the different cellular uptake profiles in cancer versus drug resistant melanoma (A375 & A375-R), mesothelioma (MSTO & MSTO-R), and glioma (rat 9L and 9L-R, and human U87 & LN18) cell lines. The results of this study demonstrate that cell penetrating peptide uptake varies with drug resistance status and cell type, likely due to changes in cell surface markers. This study provides insight into developing functional nanoplatform delivery systems in drug resistant cancer models.

Cadmium-Free Quantum Dots as Fluorescent Labels for Exosomes.

Quantum dots are attractive alternatives to organic fluorophores for the purposes of fluorescent labeling and the detection of biomarkers. They can also be made to specifically target a protein of interest by conjugating biomolecules, such as antibodies. However, the majority of the fluorescent labeling using quantum dots is done using toxic materials such as cadmium or lead due to the well-established synthetic processes for these quantum dots. Here, we demonstrate the use of indium phosphide quantum dots with a zinc sulfide shell for the purposes of labeling and the detection of exosomes derived from the THP-1 cell line (monocyte cell line). Exosomes are nano-sized vesicles that have the potential to be used as biomarkers due to their involvement in complex cell processes. However, the lack of standardized methodology around the detection and analysis of exosomes has made it difficult to detect these membrane-containing vesicles. We targeted a protein that is known to exist on the surface of the exosomes (CD63) using a CD63 antibody. The antibody was conjugated to the quantum dots that were first made water-soluble using a ligand-exchange method. The conjugation was done using carbodiimide coupling, and was confirmed using a range of different methods such as dynamic light scattering, surface plasmon resonance, fluorescent microscopy, and Fourier transform infrared spectroscopy. The conjugation of the quantum dot antibody to the exosomes was further confirmed using similar methods. This demonstrates the potential for the use of a non-toxic conjugate to target nano-sized biomarkers that could be further used for the detection of different diseases.

Interface-Dependent Selectivity in Plasmon-Driven Chemical Reactions.

Plasmonic nanoparticles can drive chemical reactions powered by sunlight. These processes involve the excitation of surface plasmon resonances (SPR) and the subsequent charge transfer to adsorbed molecular orbitals. Nonetheless, controlling the flow of energy and charge from SPR to adsorbed molecules is still difficult to predict or tune. Here, we show the crucial role of halide ions in modifying the energy landscape of a plasmon-driven chemical reaction by carefully engineering the nanoparticle-molecule interface. By doing so, the selectivity of plasmon-driven chemical reactions can be controlled, either enhancing or inhibiting the metal-molecule charge and energy transfer or by regulating the vibrational pumping rate. These results provide an elegant method for controlling the energy flow from plasmonic nanoparticles to adsorbed molecules, in situ, and selectively targeting chemical bonds by changing the chemical nature of the metal-molecule interface.

An In Vitro Investigation of Cytotoxic Effects of InP/Zns Quantum Dots with Different Surface Chemistries.

Indium phosphide quantum dots (QDs) passivated with zinc sulphide in a core/shell architecture (InP/ZnS) with different surface chemistries were introduced to RAW 264.7 murine "macrophage-like" cells to understand their potential toxicities. The InP/ZnS quantum dots were conjugated with an oligonucleotide, a carboxylic acid, or an amino-polyethylene glycol ligand, and cell viability and cell proliferation were investigated via a metabolic assay. Membrane integrity was measured through the production of lactate dehydrogenase. Fluorescence microscopy showed cellular uptake. All quantum dots exhibited cytotoxic behaviour less than that observed from cadmium- or lead-based quantum dots; however, this behaviour was sensitive to the ligands used. In particular, the amino-polyethylene glycol conjugated quantum dots proved to possess the highest cytotoxicity examined here. This provides quantitative evidence that aqueous InP/ZnS quantum dots can offer a safer alternative for bioimaging or in therapeutic applications.

Inter-ligand energy transfer in dye chromophores attached to high bandgap SiO2 nanoparticles.

Artificial light harvesters require ordered arrangement of chromophores. We covalently attach three organic chromophore ligands to silicon dioxide nanoparticles. This allows us to study inter-ligand energy transfer when attached to SiO2 nanoparticles, creating a simple system with a large ratio of donors to acceptors. Using steady-state and transient spectroscopy measurements we quantify this energy transfer between ligands. We show a maximum transfer efficiency of 30% and measure the 2D diffusion length of anthracene carboxylic acid on SiO2 to be between 0.6 and 2.2 nm.

Unraveling aminophosphine redox mechanisms for glovebox-free InP quantum dot syntheses.

The synthesis of colloidal indium phosphide quantum dots (InP QDs) has always been plagued by difficulties arising from limited P3- sources. Being effectively restricted to the highly pyrophoric tris(trimethylsilyl) phosphine (TMS3P) creates complications for the average chemist and presents a significant risk for industrially scaled reactions. The adaptation of tris(dialkylamino) phosphines for these syntheses has garnered attention, as these new phosphines are much safer and can generate nanoparticles with competitive photoluminescence properties to those from (TMS)3P routes. Until now, the reaction mechanics of this precursor were elusive due to many experimental optimizations, such as the inclusion of a high concentration of zinc salts, being atypical of previous InP syntheses. Herein, we utilize density functional theory calculations to outline a logical reaction mechanism. The aminophosphine precursor is found to require activation by a zinc halide before undergoing a disproportionation reaction to self-reduce this P(iii) material to a P(-iii) source. We use this understanding to adapt this precursor for a two-pot nanoparticle synthesis in a noncoordinating solvent outside of glovebox conditions. This allowed us to generate spherical InP/ZnS nanoparticles possessing fluorescence quantum yields >55% and lifetimes as fast as 48 ns, with tunable emission according to varying zinc halide acidity. The development of high quality and efficient InP QDs with this safer aminophosphine in simple Schlenk environments will enable a broader range of researchers to synthesize these nontoxic materials for a variety of high-value applications.

Selective assembly of Au-Fe3O4 nanoparticle hetero-dimers.

Hetero-dimeric magnetic nanoparticles of the type Au-Fe3O4 have been synthesised from separately prepared, differently shaped (spheres and cubes), monodisperse nanoparticles. This synthesis was achieved by the following steps: (a) Mono-functionalising each type of nanoparticles with aldehyde functional groups through a solid support approach, where nanoparticle decorated silica nanoparticles were fabricated as an intermediate step; (b) Derivatising the functional faces with complementary functionalities (e.g. amines and carboxylic acids); (c) Dimerising the two types of particles via amide bond formation. The resulting hetero-dimers were characterised by high-resolution TEM, Fourier transform IR spectroscopy and other appropriate methods. Graphical AbstractNano-LEGO: Assembling two types of separately prepared nanoparticles into a hetero-dimer is the first step towards complex nano-architectures. This study shows a solid support approach to combine a gold and a magnetite nanocrystal.