Radiotherapy Metastatic Prostate Cancer Cell Lines Treated with Gold Nanorods Modulate miRNA Signatures.

MicroRNA (miRNA) modulation has been identified as a promising strategy for improving the response of human prostate cancer (PCa) to radiotherapy (RT). Studies have shown that mimics or inhibitors of miRNAs could modulate the sensitivity of PCa cells to RT. In addition, pegylated gold nanoparticles have been studied as a therapeutic approach to treat PCa cells and/or vehicles for carrying miRNAs to the inside of cells. Therefore, we evaluated the capacity of hypofractionated RT and pegylated gold nanorods (AuNPr-PEG) to modulate the miRNA signature on PCa cells. Thus, RT-qPCR was used to analyze miRNA-95, miRNA-106-5p, miRNA-145-5p, and miRNA-541-3p on three human metastatic prostate cell lines (PC3, DU145, and LNCaP) and one human prostate epithelial cell line (HprEpiC, a non-tumor cell line) with and without treatment. Our results showed that miRNA expression levels depend on cell type and the treatment combination applied using RT and AuNPr-PEG. In addition, cells pre-treated with AuNPr-PEG and submitted to 2.5 Gy per day for 3 days decreased the expression levels of miRNA-95, miRNA-106, miRNA-145, and miRNA-541-3p. In conclusion, PCa patients submitted to hypofractionated RT could receive personalized treatment based on their metastatic cellular miRNA signature, and AuNPr-PEG could be used to increase metastatic cell radiosensitivity.

Chitosan/Alginate Nanogels Containing Multicore Magnetic Nanoparticles for Delivery of Doxorubicin.

In this study, multicore-like iron oxide (Fe3O4) and manganese ferrite (MnFe2O4) nanoparticles were synthesized and combined with nanogels based on chitosan and alginate to obtain a multimodal drug delivery system. The nanoparticles exhibited crystalline structures and displayed sizes of 20 ± 3 nm (Fe3O4) and 11 ± 2 nm (MnFe2O4). The Fe3O4 nanoparticles showed a higher saturation magnetization and heating efficiency compared with the MnFe2O4 nanoparticles. Functionalization with citrate and bovine serum albumin was found to improve the stability and modified surface properties. The nanoparticles were encapsulated in nanogels, and provided high drug encapsulation efficiencies (~70%) using doxorubicin as a model drug. The nanogels exhibited sustained drug release, with enhanced release under near-infrared (NIR) laser irradiation and acidic pH. The nanogels containing BSA-functionalized nanoparticles displayed improved sustained drug release at physiological pH, and the release kinetics followed a diffusion-controlled mechanism. These results demonstrate the potential of synthesized nanoparticles and nanogels for controlled drug delivery, offering opportunities for targeted and on-demand release in biomedical applications.

Development of a novel electrochemical biosensor based on plastic antibodies for detection of STEAP1 biomarker in cancer.

STEAP1 is a cell surface protein of the STEAP family whose main function focuses on intercellular communication and cell growth. STEAP1 is considered a promising putative biomarker and a candidate target for prostate cancer treatment. For specific and selective detection of STEAP1, a molecularly imprinted polymers (MIP) was developed on a screen-printed electrode (C-SPE) whose surface was modified with a nanocomposite based on carbon nanotubes decorated with dendritic platinum nanoparticles (CNTs- PAH /Pt). Then, the MIPs were produced on the modified C-SPE by electropolymerization of a mixture of STEAP1 and a monomer (pyrrole-2-carboxylic acid). Then, the protein was removed from the polymeric network by enzymatic treatment with trypsin, which created the specific template cavities for further STEAP1 detection. Electrochemical techniques such as EIS and CV were used to follow the chemical modification steps of C-SPE. The analytical performance of the biosensor was evaluated by SWV in PBS buffer and in lysates of neoplastic prostate cancer cells (LNCaP) extracts. The MIP material showing a linear range from 130 pg/ml to 13 µg/ml. Overall, the biosensor exhibits essential properties such as selectivity, sensitivity and reproducibility for its application in medical and clinical research diagnosis and/or prognosis of prostate cancer.

Metabolic Disruption of Gold Nanospheres, Nanostars and Nanorods in Human Metastatic Prostate Cancer Cells.

Nanomaterials offer a broad spectrum of applications in biomedicine. The shapes of gold nanoparticles could modulate tumor cell behavior. Spherical (AuNPsp), stars (AuNPst) and rods (AuNPr) shapes of polyethylene glycol coated-gold nanoparticles (AuNPs-PEG) were synthesized. Metabolic activity, cellular proliferation, and reactive oxygen species (ROS) were measured and the impact of AuNPs-PEG in metabolic enzymes function was evaluated by RT-qPCR in PC3, DU145, and LNCaP prostate cancer cells. All AuNPs were internalized, and the different morphologies of AuNPs showed to be an essential modulator of metabolic activity. For PC3 and DU145, the metabolic activity of AuNPs was found to rank in the following order from lowest to highest: AuNPsp-PEG, AuNPst-PEG, and AuNPr-PEG. Regarding LNCaP cells, the AuNPst-PEG were less toxic, followed by AuNPsp-PEG and AuNPr-PEG, but it seems not to be dose-dependent. The proliferation was lower in AuNPr-PEG in PC3 and DU145 cells but was stimulated around 10% in most conditions (0.001-0.1 mM) in LNCaP cells (not statistically significant). For 1 mM, LNCaP cells showed a significant decrease in proliferation only for AuNPr-PEG. The outcomes of the current study demonstrated that different AuNPs conformations influence cell behavior, and the correct size and shape must be chosen considering its final application in the field of nanomedicine.

Application of Gold Nanoparticles as Radiosensitizer for Metastatic Prostate Cancer Cell Lines.

More than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.

Nanostructured Heterogeneous Catalysts for Bioorthogonal Reactions.

Bioorthogonal chemistry has inspired a new subarea of chemistry providing a powerful tool to perform novel biocompatible chemospecific reactions in living systems. Following the premise that they do not interfere with biological functions, bioorthogonal reactions are increasingly applied in biomedical research, particularly with respect to genetic encoding systems, fluorogenic reactions for bioimaging, and cancer therapy. This Minireview compiles recent advances in the use of heterogeneous catalysts for bioorthogonal reactions. The synthetic strategies of Pd-, Au-, and Cu-based materials, their applicability in the activation of caged fluorophores and prodrugs, and the possibilities of using external stimuli to release therapeutic substances at a specific location in a diseased tissue are discussed. Finally, we highlight frontiers in the field, identifying challenges, and propose directions for future development in this emerging field.

Oxidative Precipitation Synthesis of Calcium-Doped Manganese Ferrite Nanoparticles for Magnetic Hyperthermia.

Superparamagnetic nanoparticles are of high interest for therapeutic applications. In this work, nanoparticles of calcium-doped manganese ferrites (CaxMn1-xFe2O4) functionalized with citrate were synthesized through thermally assisted oxidative precipitation in aqueous media. The method provided well dispersed aqueous suspensions of nanoparticles through a one-pot synthesis, in which the temperature and Ca/Mn ratio were found to influence the particles microstructure and morphology. Consequently, changes were obtained in the optical and magnetic properties that were studied through UV-Vis absorption and SQUID, respectively. XRD and Raman spectroscopy studies were carried out to assess the microstructural changes associated with stoichiometry of the particles, and the stability in physiological pH was studied through DLS. The nanoparticles displayed high values of magnetization and heating efficiency for several alternating magnetic field conditions, compatible with biological applications. Hereby, the employed method provides a promising strategy for the development of particles with adequate properties for magnetic hyperthermia applications, such as drug delivery and cancer therapy.

Plasmonic lipogels: driving co-assembly of composites with peptide-based gels for controlled drug release.

Supramolecular short peptide-based gels are promising materials for the controlled release of drugs (e.g. chemotherapeutic drugs) owing to the biocompatibility and similarity to cell matrix. However, the drug encapsulation and control over its release, mainly the hydrophilic drugs, can be a cumbersome task. This can be overcome through encapsulation/compartmentalization of drugs in liposomes, which can also enable spatiotemporal control and enhanced drug release through a trigger, such as photothermia. Having this in mind, we explored the assembly of silica-coated gold nanoparticles and liposomes (storage units) with dehydropeptide-based hydrogels as a proof-of-concept to afford peptide-based NIR light-responsive lipogels. Several liposomes compositions were assessed that displayed influence on the final assembly properties by combining with silica-coated gold nanorods (∼106 nm). Gold nanospheres (∼11 nm) were used to study the preparation method, which revealed the importance of initially combine liposomes with nanoparticles and then the gelator solution to achieve a closer proximity of the nanoparticles to the liposomes. The control over a hydrophilic model drug, 5(6)-carboxyfluorescein, was only achieved by its encapsulation in liposomes, in which the presence of silica-coated nanorods further enabled the use of photothermia to induce the liposomes phase transition and stimulate the drug release. Further, both composites, the liposomes and silica-coated gold nanorods, induced a lower elastic modulus, but also provided an enhanced gelation kinetics. Hereby, this work advances fabrication strategies for the development of short peptide-based hydrogels towards on-demand, sustained and controlled release of hydrophilic drugs through photothermia under NIR light irradiation.

Synergistic Interaction of Clusters of Iron Oxide Nanoparticles and Reduced Graphene Oxide for High Supercapacitor Performance.

Supercapacitors have been recognized as one of the more promising energy storage devices, with great potential use in portable electronics and hybrid vehicles. In this study, a composite made of clusters of iron oxide (Fe3O4-γFe2O3) nanoparticles and reduced graphene oxide (rGO) has been developed through a simple one-step solvothermal synthesis method for a high-performance supercapacitor electrode. Electrochemical assessment via cyclic voltammetry, galvanostatic charge-discharge experiments, and electrochemical impedance spectroscopy (EIS) revealed that the Fe3O4-γFe2O3/rGO nanocomposite showed much higher specific capacitance than either rGO or bare clusters of Fe3O4-γFe2O3 nanoparticles. In particular, specific capacitance values of 100 F g-1, 250 F g-1, and 528 F g-1 were obtained for the clusters of iron oxide nanoparticles, rGO, and the hybrid nanostructure, respectively. The enhancement of the electrochemical performance of the composite material may be attributed to the synergistic interaction between the layers of graphene oxide and the clusters of iron oxide nanoparticles. The intimate contact between the two phases eliminates the interface, thus enabling facile electron transport, which is key to attaining high specific capacitance and, consequently, enhanced charge-discharge time. Performance evaluation in consecutive cycles has demonstrated that the composite material retains 110% of its initial capacitance after 3000 cycles, making it a promising candidate for supercapacitors.

Tuning the drug multimodal release through a co-assembly strategy based on magnetic gels.

Self-assembled short peptide-based gels are highly promising drug delivery systems. However, implementing a stimulus often requires screening different structures to obtain gels with suitable properties, and drugs might not be well encapsulated and/or cause undesirable effects on the gel's properties. To overcome this challenge, a new design approach is presented to modulate the release of doxorubicin as a model chemotherapeutic drug through the interplay of (di)phenylalanine-coated magnetic nanoparticles, PEGylated liposomes and doxorubicin co-assembly in dehydropeptide-based gels. The composites enable an enhancement of the gelation kinetics in a concentration-dependent manner, mainly through the use of PEGylated liposomes. The effect of the co-assembly of phenylalanine-coated nanoparticles with the hydrogel displays a concentration and size dependence. Finally, the integration of liposomes as doxorubicin storage units and of nanoparticles as composites that co-assemble with the gel matrix enables the tuneability of both passive and active doxorubicin release through a thermal, and a low-frequency alternating magnetic field-based trigger. In addition to the modulation of the gel properties, the functionalization with (di)phenylalanine improves the cytocompatibility of the nanoparticles. Hereby, this work paves a way for the development of peptide-based supramolecular systems for on-demand and controlled release of drugs.

Tuning Peptide-Based Hydrogels: Co-Assembly with Composites Driving the Highway to Technological Applications.

Self-assembled peptide-based gels provide several advantages for technological applications. Recently, the co-assembly of gelators has been a strategy to modulate and tune gel properties and even implement stimuli-responsiveness. However, it still comprises limitations regarding the required library of compounds and outcoming properties. Hence, efforts have been made to combine peptide-based gels and (in)organic composites (e.g., magnetic nanoparticles, metal nanoparticles, liposomes, graphene, silica, clay, titanium dioxide, cadmium sulfide) to endow stimuli-responsive materials and achieve suitable properties in several fields ranging from optoelectronics to biomedical. Herein, we discuss the recent developments with composite peptide-based gels including the fabrication, tunability of gels' properties, and challenges on (bio)technological applications.

The Influence of miRNAs on Radiotherapy Treatment in Prostate Cancer - A Systematic Review.

In the last years, extensive investigation on miRNomics have shown to have great advantages in cancer personalized medicine regarding diagnosis, treatment and even clinical outcomes. Prostate cancer (PCa) is the second most common male cancer and about 50% of all PCa patients received radiotherapy (RT), despite some of them develop radioresistance. Here, we aim to provide an overview on the mechanisms of miRNA biogenesis and to discuss the functional impact of miRNAs on PCa under radiation response. As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. Identification of miRNAs panel can be thus considered an upcoming and potentially useful strategy in PCa diagnosis, given that radioresistance biomarkers, in both prognosis and therapy still remains a challenge.

Dual biorecognition by combining molecularly-imprinted polymer and antibody in SERS detection. Application to carcinoembryonic antigen.

This work reports the innovative combination of a molecularly-imprinted polymer (MIP) and a natural antibody for the accurate surface-enhanced Raman spectroscopy (SERS) detection of carcinoembryonic antigen (CEA). The MIP material acted as a pre-concentration scheme for the target protein, while the natural antibody was responsible to signal the presence of CEA on the MIP platform. Gold-based screen-printed electrodes were used as substrate and gallic acid (GA) was used herein for the first time in the assembly of a MIP film, by electropolymerization, in the presence of CEA. This layer was further covered by a second ultra-thin film of electropolymerized benzoic acid (BA), to avoid non-specific binding. The rebinding features of the MIP film were evaluated by electrochemical impedance spectroscopy (EIS) and a linear response was observed from 1 to 1000 ng/mL. For a sensitive SERS detection, the MIP film was first incubated in sample containing CEA and next incubated in SERS tag. For the SERS tag, gold nanostars (AuNSs) were employed as metal support, coupled to 4-aminothiophenol (4-ATP) as Raman reporter and to a natural antibody for CEA as recognition element. The overall system showed a sensitive response down to 1.0 ng/mL, which was different from the blank signal. Overall, the innovative approach presented herein combines the advantages of using two different targeting elements for CEA. The costs and time of MIP production were substantially low due to selection of electropolymerization approach and the proposal described herein may be extended to other target molecules.

Controlled drug delivery systems for cancer based on mesoporous silica nanoparticles.

The implementation of nanotechnology in medicine has opened new research horizons particularly in the field of therapeutic delivery. Mesoporous silica particles have emerged as biocompatible drug delivery systems with an enormous potential in the treatment of cancer among many other pathologies. In this review, we focus on the unique properties of these particles as chemotherapy delivery carriers. Here, we summarize the general characteristics of these nanomaterials - including their physicochemical properties and customizable surfaces - different stimuli that can be used to trigger targeted drug release, biocompatibility and finally, the drawbacks of these types of nanomaterials, highlighting some of the most important features of mesoporous silica nanoparticles in drug delivery.

Tobacco Mosaic Virus-Functionalized Mesoporous Silica Nanoparticles, a Wool-Ball-like Nanostructure for Drug Delivery.

The design of versatile tools to improve cell targeting and drug delivery in medicine has become increasingly pertinent to nanobiotechnology. Biological and inorganic nanocarrier drug delivery systems are being explored, showing advantages and disadvantages in terms of cell targeting and specificity, cell internalization, efficient payload delivery, and safety profiles. Combining the properties of a biological coating on top of an inorganic nanocarrier, we hypothesize that this hybrid system would improve nanoparticle-cell interactions, resulting in enhanced cell targeting and uptake properties compared to the bare inorganic nanocarrier. Toward this goal, we engineered a hierarchical assembly featuring the functionalization of cargo-loaded mesoporous silica nanoparticles (MSNPs) with tobacco mosaic virus (TMV) as a biological coating. The MSNP functions as a delivery system because the porous structure enables high therapeutic payload capacity, and TMV serves as a biocompatible coating to enhance cell interactions. The resulting MSNP@TMV nanohybrids have a wool-ball-like appearance and demonstrate enhanced cell uptake, hence cargo delivery properties. The MSNP@TMV have potential for medical applications such as drug delivery, contrast agent imaging, and immunotherapy.

SERS assisted ultra-fast peptidic screening: a new tool for drug discovery.

Herein we present a direct label-free ultra-fast method for the identification and classification of the active members of a combinatorial library directly on the solid support used for their synthesis. The method is based on the appropriate functionalization of polyethylene glycol grafted polystyrene (TentaGel®) microbeads with Au@Ag nanoparticles, the use of these materials directly as solid-phase supports for the synthesis of combinatorial libraries of peptides and the subsequent SERS analysis for identification of each peptide on each bead.