Titanium-Based Nanoarchitectures for Sonodynamic Therapy-Involved Multimodal Treatments.

Sonodynamic therapy (SDT) has considerably revolutionized the healthcare sector as a viable noninvasive therapeutic procedure. It employs a combination of low-intensity ultrasound and chemical entities, known as a sonosensitizer, to produce cytotoxic reactive oxygen species (ROS) for cancer and antimicrobial therapies. With nanotechnology, several unique nanoplatforms are introduced as a sonosensitizers, including, titanium-based nanomaterials, thanks to their high biocompatibility, catalytic efficiency, and customizable physicochemical features. Additionally, developing titanium-based sonosensitizers facilitates the integration of SDT with other treatment modalities (for example, chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy), hence increasing overall therapeutic results. This review summarizes the most recent developments in cancer therapy and tissue engineering using titanium nanoplatforms mediated SDT. The synthesis strategies and biosafety aspects of Titanium-based nanoplatforms for SDT are also discussed. Finally, various challenges and prospects for its further development and potential clinical translation are highlighted.

Chitosan-Grafted-Poly(N-vinylcaprolactam)-Decorated Fe3O4@SiO2 Core-Shell Nanoformulation as an Efficient Drug Delivery System for Poorly Soluble Drugs.

Hydrocortisone, a commonly used anti-inflammatory drug, has limited aqueous solubility and several side effects. To address this challenge, as a proof-of-concept, this article demonstrates the development of a controlled-release drug delivery system (DDS) for hydrocortisone using chitosan-grafted poly(N-vinylcaprolactam) (CS-g-PNVCL)-coated core-shell Fe3O4@SiO2 nanoformulations (NFs). Reported magnetic nanoparticles (NPs) were synthesized and modified with silica, PNVCL, and CS precursors to enhance the biocompatibility of DDS and drug-loading efficiency. The release rate of hydrocortisone from Fe3O4@SiO2@CS-g-PNVCL NFs was observed to be higher at lower pH values, and the smart polymer coating demonstrated temperature responsiveness, facilitating drug release at higher temperatures. Fe3O4@SiO2@CS-g-PNVCL NFs exhibited a cell viability of around 97.2 to 87.3% (5-100 µg/mL) after 24-48 h, while the hydrocortisone-NFs had a cell viability of around 93.2 to 82.3%. Our findings suggest that CS-g-PNVCL-coated Fe3O4@SiO2 NPs effectively enhance the solubility, loading capacity, and targeted delivery of poorly soluble drugs, thereby improving their therapeutic efficacy and bioavailability.

Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to Ex Vivo and In Vivo Tissues.

Driven by regulatory authorities and the ever-growing demands from industry, various artificial tissue models have been developed. Nevertheless, there is no model to date that is capable of mimicking the biomechanical properties of the skin whilst exhibiting the hydrophilicity/hydrophobicity properties of the skin layers. As a proof-of-concept study, tissue surrogates based on gel and silicone are fabricated for the evaluation of microneedle penetration, drug diffusion, photothermal activity, and ultrasound bioimaging. The silicone layer aims to imitate the stratum corneum while the gel layer aims to mimic the water-rich viable epidermis and dermis present in in vivo tissues. The diffusion of drugs across the tissue model is assessed, and the results reveal that the proposed tissue model shows similar behavior to a cancerous kidney. In place of typical in vitro aqueous solutions, this model can also be employed for evaluating the photoactivity of photothermal agents since the tissue model shows a similar heating profile to skin of mice when irradiated with near-infrared laser. In addition, the designed tissue model exhibits promising results for biomedical applications in optical coherence tomography and ultrasound imaging. Such a tissue model paves the way to reduce the use of animals testing in research whilst obviating ethical concerns.

Detection of Dopamine Receptors Using Nanoscale Dendrimer for Potential Application in Targeted Delivery and Whole-Body Imaging: Synthesis and In Vivo Organ Distribution.

Dopamine is one of the most important neurotransmitters released by neurons in the central nervous system, and a variety of neurological illnesses and mental disorders are associated with impairments in the secretion and functionality of dopamine. Dopamine, depending on the type of receptors, can act as a stimulant or an inhibitor. In this study, dendrimer-conjugated dopamine was utilized as a chelating agent for Technetium-99m to investigate the organ distribution of this compound in vivo using the single-photon emission computed tomography (SPECT) technique. For this purpose, dendrimers were synthesized using polyethylene glycol diacid and citric acid precursors, and dopamine was conjugated to the dendrimer using EDC/NHS cross-linker. The results showed no sign of toxicity of the dopamine-functionalized dendrimers on HEK-293 cell lines. The optimization of labeling conditions was conducted using the experimental design method (i.e., conjugate value, pH, and the amount of reducing agent), and then labeling efficiency was evaluated by thin-layer chromatography (TLC). Finally, the study of organ distribution in normal mice using SPECT imaging and comparing it with gene expression in different organs revealed that dopamine D1 receptors exhibited the highest accumulation in the liver and that the drug retained its specificity.

Novel G-CSF conjugated anionic globular dendrimer: Preparation and biological activity assessment.

The most crucial role of granulocyte colony-stimulating factor (G-CSF) in the body is to increase the strength of immune system. In recent years, research on the use of nanoparticles in pharmaceuticals has been considered, most of which have been for drug-loading purposes. In this study, a novel G-CSF conjugated dendrimer was synthesized and characterized using different techniques. In vitro cytotoxicity was assessed on A549 and L929 cells, while abnormal toxicity was studied in mice. In vitro and in vivo biological activities were assessed in NFS60 cells and rats, respectively. In addition, in vivo distribution, plasma half-life, and histopathological effect were studied in rat. The characterization tests confirmed the successful conjugation. There was no difference between G-CSF cytotoxicity before and after conjugation, and no difference with the control group. No mice showed abnormal toxicity. Although in vitro biological activity revealed both conjugated and free G-CSF promote proliferation cells, biological activity decreased significantly after conjugation about one-third of the unconjugated form. Nonetheless, in vivo biological activity of conjugated G-CSF increased by more than 2.5-fold relative to the unconjugated form, totally. Fortunately, no histopathologic adverse effect was observed in vital rat tissues. Also, in vivo distribution of the conjugate was similar to the native protein with an enhanced terminal half-life. Our data revealed that G-CSF conjugated dendrimer could be considered as a candidate to improve the in vivo biological activity of G-CSF. Moreover, multivalent capability of the dendrimer may be used for other new potentials of G-CSF in future perspectives.

Chlorambucil-Chitosan Nano-Conjugate: An Efficient Agent Against Breast Cancer Targeted Therapy.

BACKGROUND: Discovering new chemotherapy drugs and techniques with the least side effects is one of the most important and challenging issues in recent years worldwide. Chlorambucil is an anticancer drug that is still commonly used as a primary treatment in treating some cancers, but it can cause side effects. OBJECTIVE: In this study, we decided to use chitosan as a carrier to enhance the uptake of chlorambucil and reduce the toxicity of this drug. METHODS: After producing this nanoconjugate compound and analysing its structure by FTIR, DLS and AFM analysis, we investigated the therapeutic and biological effects of this nanoconjugate compound on the MCF-7 cell line (breast cancer). RESULTS: The results of the MTT assay showed that this nanoconjugate compound not only retained its anticancer effect against chlorambucil but also showed less abnormal toxicity. In addition, in vitro cellular uptake by flow cytometry indicated the better uptake final product into the MCF-7 cells. The detection of apoptosis induced cell death was confirmed by RT-PCR. CONCLUSION: This study has created a prospective pathway for targeting cancer cells using chitosan.

Novel radiopharmaceutical (Technetium-99m)-(DOTA-NHS-ester)-Methionine as a SPECT-CT tumor imaging agent.

Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals. In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high. Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice.