The use of nanoparticles for targeted drug delivery in non-small cell lung cancer.

Lung cancer is a global health problem affecting millions of people each year. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with various conventional treatment available in the clinic. Application of these treatments alone often results in high rates of cancer reoccurrence and metastasis. In addition, they can cause damage to healthy tissues, resulting in many adverse effects. Nanotechnology has emerged as a modality for the treatment of cancer. When used in combination with nanoparticles, it is possible to improve the pharmacokinetic and pharmacodynamic profiles of pre-existing drugs used in cancer treatment. Nanoparticles have physiochemical properties such as small size which allowing passage through challenging areas of the body, and large surface area allows for higher doses of drugs to be brought to the tumor site. Nanoparticles can be functionalized which involves modifying the surface chemistry of the particles and allows for the conjugation of ligands (small molecules, antibodies, and peptides). Ligands can be chosen for their ability to target components that are specific to or are upregulated in cancer cells, such as targeting receptors on the tumor surface that are highly expressed in the cancer. This ability to precisely target the tumor can improve the efficacy of drugs and decrease toxic side effects. This review will discuss approaches used for targeting drugs to tumors using nanoparticles, provide examples of how this has been applied in the clinic and highlight future prospects for this technology.

Study and Preparation of Multifunctional Poly(L-Lysine)@Hyaluronic Acid Nanopolyplexes for the Effective Delivery of Tumor Suppressive MiR-34a into Triple-Negative Breast Cancer Cells.

Non-viral gene delivery using exogenous microRNAs is a potential strategy for fighting cancers with poor prognosis and which lack specific therapies, such as triple-negative breast cancer (TNBC). Herein we report the synthesis of six nontoxic electrostatic polymeric nanocapsules (P1 to P6) for microRNA delivery in TNBC cells. 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy (SEM) were used to characterize the nanopolyplexes, synthesized with Poly(L-Lysine) and hyaluronic acid (Ha). Studies on the activity of the ternary HA/PLI/miRNA-34 nanopolyplexes towards TNBC cell line MDA-MB-231 were conducted. The nanopolyplexes mediated intracellular restoration of tumor suppressor miR34a was evaluated by using Western blotting to quantify the expression level of the Bcl-2 protein. The results suggest that the P5, with a ratio PLI/Ha of 0.05, was the most promising for the delivery of miR-34a into TNBC cells; the P5 nanocapsules were able to reduce Bcl-2 expression at a protein level, and had an effect in the overall cell viability after 24 h treatment.

Synthesis of Gold Functionalised Nanoparticles with the Eranthis hyemalis Lectin and Preliminary Toxicological Studies on Caenorhabditis elegans.

The lectin found in the tubers of the Winter Aconite (Eranthis hyemalis) plant (EHL) is a Type II Ribosome Inactivating Protein (RIP). Type II RIPs have shown anti-cancer properties and have great potential as therapeutic agents. Similarly, colloidal gold nanoparticles are successfully used in biomedical applications as they can be functionalised with ligands with high affinity and specificity for target cells to create therapeutic and imaging agents. Here we present the synthesis and characterization of gold nanoparticles conjugated with EHL and the results of a set of initial assays to establish whether the biological effect of EHL is altered by the conjugation. Gold nanoparticles functionalised with EHL (AuNPs@EHL) were successfully synthesised by bioconjugation with citrate gold nanoparticles (AuNPs@Citrate). The conjugates were analysed by UV-Vis spectroscopy, Dynamic Light Scattering (DLS), Zeta Potential analysis, and Transmission Electron Microscopy (TEM). Results indicate that an optimal functionalisation was achieved with the addition of 100 µL of EHL (concentration 1090 ± 40 µg/mL) over 5 mL of AuNPs (concentration [Au°] = 0.8 mM). Biological assays on the effect of AuNPs@EHL were undertaken on Caenorhabditis elegans, a free-living nematode commonly used for toxicological studies, that has previously been shown to be strongly affected by EHL. Citrate gold nanoparticles did not have any obvious effect on the nematodes. For first larval stage (L1) nematodes, AuNPs@EHL showed a lower biological effect than EHL. For L4 stage, pre-adult nematodes, both EHL alone and AuNPs@EHL delayed the onset of reproduction and reduced fecundity. These assays indicate that EHL can be conjugated to gold nanoparticles and retain elements of biocidal activity.

Green and Red Fluorescent Dyes for Translational Applications in Imaging and Sensing Analytes: A Dual-Color Flag.

Invited for this month's cover picture is the BIOSCOPE group of Professors Carlos Lodeiro and José Luis Capelo at the REQUIMTE/UCIBIO-LAQv-FCT University NOVA of Lisbon (Portugal), and their collaborators. The cover picture is devoted to Translational Research, and shows the Portuguese Flag represented by the interaction between cells and Janus gold/silver nanoparticles functionalized with rhodamine (red) and Fluorescein (green) dyes as tools for biomedical translational research. Read the full text of their Review at 10.1002/open.201700135.

Green and Red Fluorescent Dyes for Translational Applications in Imaging and Sensing Analytes: A Dual-Color Flag.

Red and green are two of the most-preferred colors from the entire chromatic spectrum, and red and green dyes are widely used in biochemistry, immunohistochemistry, immune-staining, and nanochemistry applications. Selective dyes with green and red excitable chromophores can be used in biological environments, such as tissues and cells, and can be irradiated with visible light without cell damage. This critical review, covering a period of five years, provides an overview of the most-relevant results on the use of red and green fluorescent dyes in the fields of bio-, chemo- and nanoscience. The review focuses on fluorescent dyes containing chromophores such as fluorescein, rhodamine, cyanine, boron-dipyrromethene (BODIPY), 7-nitobenz-2-oxa-1,3-diazole-4-yl, naphthalimide, acridine orange, perylene diimides, coumarins, rosamine, Nile red, naphthalene diimide, distyrylpyridinium, benzophosphole P-oxide, benzoresorufins, and tetrapyrrolic macrocycles. Metal complexes and nanomaterials with these dyes are also discussed.

Unraveling the Organotellurium Chemistry Applied to the Synthesis of Gold Nanomaterials.

Long-term preservation of the properties of gold nanoparticles in both solution and the dry powder form can be difficult. We have overcome this challenge by using organotellurium derivatives as both reducing agents and stabilizers in the synthesis of gold nanoparticles. This new synthetic protocol takes advantage of the photochemical and oxidative properties of diphenyl ditelluride (Ph2Te2), which, so far, have never been exploited in the synthesis of gold nanoparticles. The Au/Te core/shell (inorganic/organic) hybrid nanomaterial can be obtained in a one-step reaction, using only Ph2Te2 and HAuCl4. By modifying the reaction conditions, different resonance conditions of the gold core are achieved due to the formation of external shells with different thicknesses. The organotellurium shell can be easily removed by resuspension of the nanoparticles in environmentally friendly solvents, such as water or ethanol, making the Au core available for subsequent applications. A mechanism for the formation of core/shell nanoparticles has also been discussed.

Winter Aconite (Eranthis hyemalis) Lectin as a cytotoxic effector in the lifecycle of Caenorhabditis elegans.

The lectin found in the tubers of the Winter Aconite (Eranthis hyemalis) plant is an N-acetyl-D-galactosamine specific Type II Ribosome Inactivating Protein (RIP); Type II RIPs have shown anti-cancer properties, and hence have potential as therapeutic agents. Here we present a modified protocol for the extraction and purification of the E. hyemalis lectin (EHL) using affinity chromatography. De novo amino acid sequencing of EHL confirms its classification as a Type II Ribosome Inactivating Protein. The biocidal properties of EHL have been investigated against the nematode Caenorhabditis elegans. Arrested first stage larvae treated with EHL have shown some direct mortality, with surviving larvae subsequently showing a range of phenotypes including food avoidance, reduced fecundity, developmental delay and constitutive dauer larvae formation. Both inappropriate dauer larvae development and failure to locate to bacterial food source are consistent with the disruption of chemosensory function and the ablation of amphid neurons. Further investigation indicates that mutations that disrupt normal amphid formation can block the EHL-induced dauer larvae formation. In combination, these phenotypes indicate that EHL is cytotoxic and suggest a cell specific activity against the amphid neurons of C. elegans.

Steady-state and time-resolved investigations on pyrene-based chemosensors.

Two novel fluorescent probes bearing a single (P) and two (a podand-like structure, L) pyrene units derived from 1,5-bis(2-aminophenoxy)-3-oxopentane have been synthesized and investigated in dioxane using UV-vis absorption, and steady-state and time-resolved (in a picosecond time scale) emission spectroscopy; in the gas phase, matrix-assisted laser desorption ionization mass spectrometry was employed. In dioxane, the absorption and emission spectra of P present a unique band with maxima at 361 and 392 nm, which have been associated with the monomer absorption and emission bands, respectively. In dioxane, for compound L, an additional band with a maximum at ∼525 nm is observed; upon the addition of water, an emissive band (with maxima varying from 405 to 490 nm) appears in both P and L spectra; this is discussed in terms of the emission of a species with charge character. Upon metal addition (Cu(2+), Zn(2+), and Ag(+)) to P, a gradual quenching effect of the monomer emission is observed and found to be more pronounced with Cu(2+). In the case of L, upon the addition of metal cations, the long emission band (∼550 nm) decreases and the monomer emission band increases (with an isoemissive point at ∼450 nm) and no evidence for the intermediate band (at ∼405-490 nm) now exists. Time-resolved data in dioxane/water mixtures showed that for P and L these two fit double- and triple-exponential decay laws, respectively. With P, this has been attributed to a two-state system, which involves the monomer and a charged species, with its emission maxima varying with the polarity of the media (here mirrored by its dielectric constant), which can potentially be addressed to an exciplex-like species, whereas with L, it has been attributed to a three-state system involving, in addition to these two species, an excimer. From absorption and fluorescence excitation and time-resolved data, evidence is given for the presence of intramolecular dimer formation in the ground state.