Fluorescent carbon quantum dots-based prodrug nanosponges with outstanding tumor-specific drug delivery and imaging

Carbon quantum dots (CQD)-based nanosponges have been widely designed for tumor theranostic application recently. However, the drug content is usually lower with the shorter dynamic covalent linkers while the longer hydrophilic dynamic covalent linkers led to a significant premature drug leakage. Here, a hydrophobic linear reducible-responsive linker with two terminal aldehyde group was designed to crosslink the hydrazine-functionalized PEGylated CQDs (Hy-CQD-PEG), resulting in Hy-CQDss-PEG nanosponges. After doxorubicin (DOX) conjugation, the DOX-Hy-CQDss-PEG prodrug nanosponges were obtained with DOX content of 18.76 % and hydrodynamic diameter of 140 nm, respectively. The DOX-Hy-CQDss-PEG nanosponges were stable in the normal physiological medium with very low drug leakage and fluorescence, while they could disintegrate in the tumor intracellular microenvironment, releasing DOX and the hydrazine-functionalized CQDs for theranostic application.     

Emerging Plasmonic Assemblies Triggered by DNA for Biomedical Applications

Plasmonic gold nanocrystal represents plasmonic metal nanomaterials, and has a variety of unique and beneficial properties, such as optical signal enhancement, catalytic activity, and photothermal properties tuned by local temperature, which are useful in physical, chemical, and biological applications. In addition, the inherent properties of predictable programmability, sequence specificity, and structural plasticity provide DNA nanostructures with precise controllability, spatial addressability, and targeting recognition, serving as ideal ligands to link or position building blocks during the self-assembly process. Self-assembly is a common technique for the organization of prefabricated and discrete nanoparticle blocks for the construction of extremely sophisticated nanocomposites. To this end, the integration of DNA nanotechnology with Au nanomaterials, followed by assembly of DNA-functionalized Au nanomaterials can form novel functional Au nanomaterials that are difficult to obtain through conventional methods. Here, recent progress in DNA-assembled Au nanostructures of various shapes is summarized, and their functions are discussed. The fabrication strategies that employ DNA for the self-assembly of Au nanostructures, including dimers, tetramers, satellites, nanochains, and other nanostructures with more complex geometric configurations are first described. Then, the characteristic optical properties and applications of biosensing, bioimaging, drug delivery, and therapy are discussed. Finally, the remaining challenges and prospects are elucidated.     

Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.     

In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model

Recent biotechnological applications in the field of clinical oncology led to the identification of new biomarkers as molecular targets of cancer, and to broad developments in the field of personalized medicine. Aptamers are oligonucleotides (ssDNA or RNA) that are selected to specifically recognize a molecular target with high affinity and specificity. Based on this, new horizons for their use as molecular imaging probes are being explored. The objective of this work was to evaluate the Sgc8-c aptamer conjugated with Alexa Fluor 647 fluorophore as an imaging probe in a colon tumor xenograft mouse model, with potential application in molecular imaging. In this study, the LS174T cell line was used to induce colorectal adenocarcinoma in nude mice. After confirmation of PTK7 overexpression by immunohistochemistry, in vivo studies were performed. Pharmacokinetic, in vivo and ex vivo biodistribution imaging, and a competition assay were evaluated by fluorescence imaging. In vivo visualization of the probe in the tumors was assessed two hours after aptamer probe administration, exhibiting excellent tumor-to-background ratios in biodistribution studies and high specificity in the competition test. Our results demonstrated the functionality of Scg8-c as an imaging probe for colon cancer, with potential clinical applications.     

Simultaneous Activation of Short‐Wave Infrared (SWIR) Light and Paramagnetism by a Functionalized Shell for High Penetration and Spatial Resolution Theranostics

Nanoparticle emitting short‐wave infrared (SWIR) light has received increased attention in the molecular imaging field due to its deeper tissue penetration, fast imaging, high sensitivity, and resolution. The simultaneously activated SWIR excited directly by an 808 nm laser and T₁‐weighted magnetic resonance imaging (MRI) signal are found in one single‐shell nanoparticle NaErF₄@NaGdF₄ (Er@Gd), which is used as a dual‐modality imaging contrast agent in vivo to accurately determine the position of tumors. The conjugated cypate is then aggregated on the surface of Er@Gd@SiO₂‐Cy/bovine serum albumin. With the guidance of dual modality imaging, photothermal therapy is effectively used to ablate tumors in a mouse model. The design of single‐shell nanomaterial activation of SWIR imaging and MRI signals is expected to provide a new strategy for high penetration and spatial resolution cancer theranostics.     

A Novel Nanoprobe for Multimodal Imaging Is Effectively Incorporated into Human Melanoma Metastatic Cell Lines

To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T₁ relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.