Aptamer-Enabled Nanomaterials for Therapeutics, Drug Targeting and Imaging

A wide variety of nanomaterials have emerged in recent years with advantageous properties for a plethora of therapeutic and diagnostic applications. Such applications include drug delivery, imaging, anti-cancer therapy and radiotherapy. There is a critical need for further components which can facilitate therapeutic targeting, augment their physicochemical properties, or broaden their theranostic applications. Aptamers are single-stranded nucleic acids which have been selected or evolved to bind specifically to molecules, surfaces, or cells. Aptamers can also act as direct biologic therapeutics, or in imaging and diagnostics. There is a rich field of discovery at the interdisciplinary interface between nanomaterials and aptamer science that has significant potential across biomedicine. Herein, we review recent progress in aptamer-enabled materials and discuss pending challenges for their future biomedical application.

Functionalized Nanomaterials as Tailored Theranostic Agents in Brain Imaging

Functionalized nanomaterials of various categories are essential for developing cancer nano-theranostics for brain diseases; however, some limitations exist in their effectiveness and clinical translation, such as toxicity, limited tumor penetration, and inability to cross blood–brain and blood-tumor barriers. Metal nanomaterials with functional fluorescent tags possess unique properties in improving their functional properties, including surface plasmon resonance (SPR), superparamagnetism, and photo/bioluminescence, which facilitates imaging applications in addition to their deliveries. Moreover, these multifunctional nanomaterials could be synthesized through various chemical modifications on their physical surfaces via attaching targeting peptides, fluorophores, and quantum dots (QD), which could improve the application of these nanomaterials by facilitating theranostic modalities. In addition to their inherent CT (Computed Tomography), MRI (Magnetic Resonance Imaging), PAI (Photo-acoustic imaging), and X-ray contrast imaging, various multifunctional nanoparticles with imaging probes serve as brain-targeted imaging candidates in several imaging modalities. The primary criteria of these functional nanomaterials for translational application to the brain must be zero toxicity. Moreover, the beneficial aspects of nano-theranostics of nanoparticles are their multifunctional systems proportioned towards personalized disease management via comprising diagnostic and therapeutic abilities in a single biodegradable nanomaterial. This review highlights the emerging aspects of engineered nanomaterials to reach and deliver therapeutics to the brain and how to improve this by adopting the imaging modalities for theranostic applications.

Radioactive nuclei for β + γ PET and theranostics: selected candidates

Positron emission tomography (PET) is an established medical diagnostic imaging method. Continuous improvements are aimed at refining image reconstruction, reducing the amount of radioactive tracer and combining with targeted therapy. Time-of-flight (TOF)-PET provides the localization of the tracer through improved time resolution, nuclear physics may contribute to this goal via selection of radioactive nuclei emitting additional γ-rays. This additional radiation, when properly detected, localizes the decay of the tracer at the line of response (LoR) determined by two detected 511 keV quanta. Selected candidates are presented. Some are particularly interesting, as they are strong candidates for theranostic applications.

Humanization, Radiolabeling and Biodistribution Studies of an IgG1-Type Antibody Targeting Uncomplexed PSA for Theranostic Applications

Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A”-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications.

Wet chemical development of CuO/GO nanocomposites: its augmented antimicrobial, antioxidant, and anticancerous activity

This study employed a bottom-up technique to synthesize copper oxide (CuO) nanoparticles over hydrophilic graphene oxide (GO) nanosheets. The CuO/GO nanocomposite has been prepared using two selected precursors of copper nitrate and citric acid with an intermittent mixing of GO solutions. The synthesized Nanocomposites were characterized using different biophysical techniques like FT-IR, NMR, FE-SEM, and HR-TEM analyses. FT-IR analyses confirm the nanocomposites’ successful formation, which is evident from the functional groups of C=C, C-O, and Cu-C stretching vibrations. Morphological analyses reveal the depositions of CuO nanoparticles over the planar rough GO sheets, which has been elucidated from the FE-SEM and HR-TEM analyses supported by respective EDAX analyses. The antimicrobial activities have been evident from the surface roughness and damages seen from the FE-SEM analyses. The CuO/GO sheets were tested against Gram-positive (e.g., Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa). It is evident that the intrinsic antibacterial activity of CuO/GO sheets, when combined in equal proportions, elicited a robust antibacterial activity when tested over Gram –ve representative bacteria Escherichia coli. The antioxidant behaviour of synthesized CuO/GO nanocomposite was evaluated by scavenging the free radicals of DPPH and ABTS. Moreover, the cytotoxic activity was also studied against epidermoid carcinoma cell line A-431. A brief mathematical formulation has been proposed in this study to uncover the possibilities of using the nanocomposites as potential drug candidates in theranostic applications in disease treatment and diagnosis. This study would help uncover the electronic properties that play in the nano-scaled system at the material-bio interface, which would aid in designing a sensitive nano-electromechanical device bearing both the therapeutic and diagnostic attributes heralding a new horizon in the health care systems.

Application in Nanomedicine of Manganese-Zinc Ferrite Nanoparticles

Besides the study and the medical application of iron oxide nanoparticles, ferrites produced with zinc and manganese are of particular interest for their properties. The introduction of these elements into the crystalline structure of the magnetic particle generates some changes in the material properties, enhancing their potential use in theranostic applications. This review will cover the most important aspects of the preparation of these materials, taking into account the different methods of synthesis, and will analyze the most promising results in their use in MRI, magnetic hyperthermia and other emerging applications.

Theranostic Applications of Nanomaterials in Alzheimer’s Disease: A multifunctional Approach

: The blood–brain barrier (BBB) prevents the transfer of many therapeutic drugs across the brain. Therefore, the leading treatment strategies of Alzheimer’s disease (AD) are seen often unsuccessful. A further challenge is to achieve specific targetability across BBB and diagnosis. Herein, theranostic based strategies are emerging to combine therapeutic, targeting, and diagnostic capabilities. Recent nanotechnological advancements enable a common podium for formulation and development of efficient theranostics. This can be attained by engineering of some of the properties of nanomaterials, thus enabling them to become an efficient and suitable theranostic. In this review, we are discussing the various novel approaches of theranostic nanomaterials owing to multimodal functionality across the brain as an effective and probable treatment as well as early (timely) diagnosis of Alzheimer’s disease. In this respect, we conducted a PubMed search to review the latest development in theranostic nanomaterials especially for Alzheimer’s (major type of dementia) therapy that led us to discuss the present theranostic nanomaterials utilizing drug carriers and include cargo, targeting ligands, and imaging agents for delivery to particular tissues, cells, or subcellular components. Our focus is on strategies for syntheses, but we will also consider the challenges and prospects associated with this evolving technology. The current review includes knowledge of the history, overview of AD, and therapeutics with a future approach of using theranostic nanomaterials as personalized medicines.

Fibroblast-Activated Protein Inhibitor PET/CT: Cancer Diagnosis and Management

Fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), is a novel target for molecular imaging of various tumors. Recently, the development of several small-molecule FAP inhibitors for radiolabeling with 68Ga has resulted in the emergence of studies evaluating its clinical role in cancer imaging. Preliminary findings have demonstrated that, in contrast to radiotracers taking advantage of cancer-specific targets such as PSMA and DOTATATE, FAPs as a target are the most promising that can compete with 18FDG in terms of widespread indications. They also have the potential to overcome the shortcomings of 18FDG, particularly false-positive uptake due to inflammatory or infectious processes, low sensitivity in certain cancer types, and radiotherapy planning. In addition, the attractive theranostic properties may facilitate the treatment of many refractory cancers. This review summarizes the current FAP variants and related clinical studies, focusing on radiopharmacy, dosimetry, and diagnostic and theranostic applications.