Investigating Tobacco's Impact on DNA Repair Genes and Risks in Oral Precancer and Cancer: A Comprehensive Research Study.

Objective: This study aimed to explore genetic variations associated with DNA repair mechanisms to enhance the management of both oral cancer (OC) and oral precancer (OPC). Methods: A cohort of 380 patients diagnosed with OC and OPC, comprising 220 males and 160 females, was analyzed. Participants were categorized based on their tobacco-chewing habits, with corresponding control groups established. Key genetic markers investigated for polymorphisms included OGG1, APE1, and XRCC1. Results: The XRCC1 Arg280H variant demonstrated significant associations with the susceptibility to both OC and OPC across various models. Further analyses, incorporating factors such as tobacco and alcohol consumption, unveiled a correlation between the XRCC1 Arg194Trp variant and an elevated risk of developing head and neck cancer. Stratified analyses also revealed an increased risk of OC or OPC based on the specific site of the cancer. Conclusion: The study underscores the importance of XRCC1 polymorphisms, particularly XRCC1 Arg280H and XRCC1 Arg194Trp, within the genetic framework of OC and OPC. Understanding these genetic associations provides valuable insights for the potential development of targeted interventions aimed at individuals predisposed to these conditions.

3D Printed Nanosensors for Cancer Diagnosis: Advances and Future Perspective.

Cancer is the leading cause of mortality worldwide, requiring continuous advancements in diagnosis and treatment. Traditional methods often lack sensitivity and specificity, leading to the need for new methods. 3D printing has emerged as a transformative tool in cancer diagnosis, offering the potential for precise and customizable nanosensors. These advancements are critical in cancer research, aiming to improve early detection and monitoring of tumors. In current times, the usage of the 3D printing technique has been more prevalent as a flexible medium for the production of accurate and adaptable nanosensors characterized by exceptional sensitivity and specificity. The study aims to enhance early cancer diagnosis and prognosis by developing advanced 3D-printed nanosensors using 3D printing technology. The research explores various 3D printing techniques, design strategies, and functionalization strategies for cancer-specific biomarkers. The integration of these nanosensors with detection modalities like fluorescence, electrochemical, and surface-enhanced Raman spectroscopy is also evaluated. The study explores the use of inkjet printing, stereolithography, and fused deposition modeling to create nanostructures with enhanced performance. It also discusses the design and functionalization methods for targeting cancer indicators. The integration of 3D-printed nanosensors with multiple detection modalities, including fluorescence, electrochemical, and surface-enhanced Raman spectroscopy, enables rapid and reliable cancer diagnosis. The results show improved sensitivity and specificity for cancer biomarkers, enabling early detection of tumor indicators and circulating cells. The study highlights the potential of 3D-printed nanosensors to transform cancer diagnosis by enabling highly sensitive and specific detection of tumor biomarkers. It signifies a pivotal step forward in cancer diagnostics, showcasing the capacity of 3D printing technology to produce advanced nanosensors that can significantly improve early cancer detection and patient outcomes.

Amelioration of breast cancer therapies through normalization of tumor vessels and microenvironment: paradigm shift to improve drug perfusion and nanocarrier permeation.

Breast cancer (BC) is the most commonly diagnosed cancer among women. Chemo-, immune- and photothermal therapies are employed to manage BC. However, the tumor microenvironment (TME) prevents free drugs and nanocarriers (NCs) from entering the tumor premises. Formulation scientists rely on enhanced permeation and retention (EPR) to extravasate NCs in the TME. However, recent research has demonstrated the inconsistent nature of EPR among different patients and tumor types. In addition, angiogenesis, high intra-tumor fluid pressure, desmoplasia, and high cell and extracellular matrix density resist the accumulation of NCs in the TME. In this review, we discuss TME normalization as an approach to improve the penetration of drugs and NCSs in the tumor premises. Strategies such as normalization of tumor vessels, reversal of hypoxia, alleviation of high intra-tumor pressure, and infiltration of lymphocytes for the reversal of therapy failure have been discussed in this manuscript. Strategies to promote the infiltration of anticancer immune cells in the TME after vascular normalization have been discussed. Studies strategizing time points to administer TME-normalizing agents are highlighted. Mechanistic pathways controlling the angiogenesis and normalization processes are discussed along with the studies. This review will provide greater tumor-targeting insights to the formulation scientists.

Combinatorial Delivery of Docetaxel- and Erlotinib-Loaded Functionalized Nanostructured Lipid Carriers for the Treatment of Triple-Negative Breast Cancer Using Quality-by-Design Approach.

This study explored the combined administration of docetaxel (DOC) and erlotinib (ERL) using nanostructured lipid carriers (NLCs), with folic acid (FA) conjugation to enhance their synergistic anticancer efficacy against triple-negative breast cancer. NLCs were developed through hot melt homogenization-ultrasound dispersion, and optimized by a quality-by-design (QbD) approach using Plackett-Burman design and Box-Behnken design. Plots were generated based on maximum desirability. Spherical, nanosized dispersions (<200 nm) with zeta potential ranging from -16.4 to -14.15 mV were observed. These nanoformulations demonstrated ~95% entrapment efficiency with around 5% drug loading. Stability tests revealed that the NLCs remained stable for 6 months under storage conditions at 4 °C. In vitro release studies indicated sustained release over 24 h, following Higuchi and Korsmeyer-Peppas models for NLCs and FA NLCs, respectively. Additionally, an in vitro pH-stat lipolysis model exhibited a nearly fivefold increase in bioaccessibility compared to drug-loaded suspensions. The DOC-ERL-loaded formulations exhibited dose- and time-dependent cytotoxicity, revealing synergism at a 1:3 molar ratio in MDA-MB-231 and 4T1 cells, with combination indices of 0.35 and 0.37, respectively. Co-treatment with DOC-ERL-loaded FA NLCs demonstrated synergistic anticancer effects in various in vitro assays.

Unravelling the role of tumor microenvironment responsive nanobiomaterials in spatiotemporal controlled drug delivery for lung cancer therapy.

Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli-physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)-that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals.

Exploration of Abiraterone acetate loaded Nanostructured lipid carriers for bioavailability improvement and circumvention of fast-fed variability.

Abiraterone acetate (ABA), a biopharmaceutical class IV drug suffers from solubility and permeability pitfalls resulting in limited oral bioavailability and positive food effect, i.e. multi-fold enhancement in drug absorption in the presence of food. This poses difficulties to physicians towards the estimation of dose and dosage regimen required for efficacious therapy of prostate cancer (PCa). Nanostructured lipid carriers (NLC) have demonstrated tremendous outcomes in enhancing the oral bioavailability of various entities along with food effect attenuation. In this study, Quality by design and multivariate analysis was employed for optimization of ABA loaded NLC (ABA NLC). The optimal size, PDI and zeta potential obtained using QbD were 134.6 nm, 0.163 and -15.7 mV respectively. Ex vivo qualitative and quantitative intestinal permeability studies demonstrated improved traversion of NLC through the intestinal segments. In vitro dissolution profile in biorelevant fast and fed gastric and intestinal media revealed minimal differences for ABA NLC compared to ABA. In vivo pharmacokinetics was performed to decipher the efficacy of ABA NLC in mitigating the food effect of ABA. The studies demonstrated 14.51-fold and 1.94-fold improvement in oral bioavailability during fasted and fed state respectively as compared to free ABA. The absorption mechanism of ABA NLC using chylomicron flow blocking approach conveyed lymphatic uptake as the major mechanism. Cmax fast/fed ratio was 0.9758 whereas, AUC fast/fed ratio was 0.9386, which being nearly equivalent, confirmed the food effect attenuation. Therefore, the results of the study demonstrate optimal pharmacokinetics of ABA NLC and its utility in circumventing the fast fed variability.

Construction, Features and Regulatory Aspects of Organ-Chip for Drug Delivery Applications: Advances and Prospective.

Organ-on-chip is an innovative technique that emerged from tissue engineering and microfluidic technologies. Organ-on-chip devices (OoCs) are anticipated to provide efficient resolutions to dealing with challenges in pharmaceutical advancement and individualized illness therapies. Organ-on-chip is an advanced method that can replicate human organs' physiological conditions and functions on a small chip. It possesses the capacity to greatly transform the drug development process by enabling the simulation of diseases and the testing of drugs. Effective integration of this advanced technical platform with common pharmaceutical and medical contexts is still a challenge. Microfluidic technology, a micro-level technique, has become a potent tool for biomedical engineering research. As a result, it has revolutionized disciplines including physiological material interpreting, compound detection, cell-based assay, tissue engineering, biological diagnostics, and pharmaceutical identification. This article aims to offer an overview of newly developed organ-on-a-chip systems. It includes single-organ platforms, emphasizing the most researched organs, including the heart, liver, blood arteries, and lungs. Subsequently, it provides a concise overview of tumour-on-a-chip systems and emphasizes their use in the evaluation of anti-cancer medications.

Resveratrol-Ampicillin Dual-Drug Loaded Polyvinylpyrrolidone/Polyvinyl Alcohol Biomimic Electrospun Nanofiber Enriched with Collagen for Efficient Burn Wound Repair.

Background: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries. Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair. Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31±0.09 mm and 12±0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10. Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.

Regulatory landscape and challenges in CAR-T cell therapy development in the US, EU, Japan, and India.

Chimeric Antigen Receptor-T cell (CAR-T) therapy has evolved as a revolutionary cancer treatment modality, offering remarkable clinical responses by harnessing the power of a patient's immune system to target and eliminate cancer cells. However, the development and commercialization of CAR-T cell therapies are accompanied by complex regulatory requirements and challenges. This therapy falls under the regulatory category of advanced therapy medicinal products. The regulatory framework and approval tools of regenerative medicine, especially CAR-T cell therapies, vary globally. The present work comprehensively analyses the regulatory landscape and challenges in CAR-T cell therapy development in four key regions: the United States, the European Union, Japan, and India. This work explores the unique requirements and considerations for preclinical studies, clinical trial design, manufacturing standards, safety evaluation, and post-marketing surveillance in each jurisdiction. Due to their complex nature, developers and manufacturers face several challenges. In India, despite advancements in treatment protocols and government-sponsorships, there are still several difficulties regarding access to treatment for the increasing number of cancer patients. However, India's first indigenously developed CAR-T cell therapy, NexCAR19, for B-cell lymphoma or leukemia, approved and available at a low cost compared to other available CAR-T therapies, raises great hope in the battle against cancer. Several strategies are proposed to address the identified hurdles from global and Indian perspectives. It discusses the benefits of aligning regulatory requirements across regions, eventually facilitating international development and enabling access to this transformative therapy.

Targeted Treatment Strategies for Mitochondria Dysfunction: Correlation with Neurological Disorders.

Mitochondria are an essential intracellular organelle for medication targeting and delivery since they seem to create energy and conduct many other cellular tasks, and mitochondrial dysfunctions and malfunctions lead to many illnesses. Many initiatives have been taken to detect, diagnose, and image mitochondrial abnormalities, and to transport and accumulate medicines precisely to mitochondria, all because of special mitochondrial aspects of the pathophysiology of cancer. In addition to the negative membrane potential and paradoxical mitochondrial dynamics, they include high temperatures, high levels of reactive oxygen species, high levels of glutathione, and high temperatures. Neurodegenerative diseases represent a broad spectrum of debilitating illnesses. They are linked to the loss of certain groups of neurons based on an individual's physiology or anatomy. The mitochondria in a cell are generally accepted as the authority with respect to ATP production. Disruption of this system is linked to several cellular physiological issues. The development of neurodegenerative disorders has been linked to mitochondrial malfunction, according to pathophysiological studies. There seems to be substantial evidence connecting mitochondrial dysfunction and oxidative stress to the development of neurodegenerative disorders. It has been extensively observed that mitochondrial malfunction triggers autophagy, which plays a role in neurodegenerative disorders. In addition, excitotoxicity and mitochondrial dysfunction have been linked to the development of neurodegenerative disorders. The pathophysiology of neurodegenerative illnesses has been linked to increased apoptosis and necrosis, as well as mitochondrial malfunction. A variety of synthetic and natural treatments have shown efficacy in treating neurodegenerative illnesses caused by mitochondrial failure. Neurodegenerative illnesses can be effectively treated with existing drugs that target mitochondria, although their precise formulations are poorly understood. Therefore, there is an immediate need to focus on creating drug delivery methods specifically targeted at mitochondria in the treatment and diagnosis of neurodegenerative disorders.

Quality by design empowered preparation of itraconazole albumin nanoparticles for prostate cancer.

The current advent explores the potential of itraconazole (ITR) in prostate cancer (PCa), by its incorporation into albumin nanoparticles (NP). ITR as a repurposed moiety has displayed tremendous potential in various cancers. However, poor aqueous solubility poses hurdles towards its clinical translation. Amorphisation of ITR was observed post-incorporation within NP matrix which could prevent its precipitation in aqueous media. ITR NP was developed using quality by design and multivariate analysis and evaluated for cellular uptake, cell proliferation inhibition and the mechanism of PCa cell inhibition. Time and concentration-dependent serum stability and hemolytic potential revealed safety of ITR NP. Morphological changes and nuclear staining studies revealed the efficacy of ITR and ITR NP in promoting growth inhibition of PC-3 cells. Superior qualitative and quantitative uptake, reactive oxygen species (ROS) and mitochondrial impairment for ITR NP in comparison with ITR and control group was observed. Cell cycle study revealed remarkable G2/M phase inhibition in PC-3 cells. ITR NP demonstrated superior anticancer potential in 3D tumoroids mimicking the micro-metastatic lesions compared to control and ITR. Hence, ITR NP can be a favorable alternative therapeutic alternative in PCa.

High mobility group box 1 cytokine targeted topical delivery of resveratrol embedded nanoemulgel for the management of atopic dermatitis.

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180-230 nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel.

Quality by design fostered fabrication of cabazitaxel loaded pH-responsive Improved nanotherapeutics against prostate cancer.

Cabazitaxel has been approved for the treatment of prostate cancer since 2010. However, its poor solubility and permeability pitfalls prevent its accumulation at the target site and promote severe adverse effects. About 90% of prostate cancer (PCa) patients suffer from bone metastasis. This advent reports the development of CBZ-loaded pH-responsive polydopamine nanoparticles (CBZ NP) against metastatic PCa cells. Quality by design (QbD) and multivariate analysis tools were employed for the optimization of CBZ NP. Amorphisation of CBZ along with metastatic microenvironment responsive release was observed thereby imparting spatial release and circumventing solubility pitfalls. CBZ NP retained its cytotoxic potential, with a significant increase in quantitative cellular uptake. Apoptotic markers observed from nuclear staining with elevated reactive oxygen species (ROS) and mitochondrial damage revealed by JC-1 staining demonstrated the efficacy of CBZ NP against PC-3 cells with good serum stability and diminished hemolysis. Cell cycle analysis revealed substantial S and G2/M phase arrest with enhancement in apoptosis was observed. Western blot studies revealed an elevation in caspase-1 and suppression in Bcl-2 indicating enhanced apoptosis compared to the control group. Substantial reduction in the diameter of 3D-Tumoroid and enhanced cell proliferation inhibition indicated the efficacy of CBZ NP in PCa. Thus, we conclude that CBZ NP could be a promising Nanotherapeutic approach for PCa.

Sulfo-butyl ether ß-cyclodextrin inclusion complexes of bosutinib: in silico, in vitro and in vivo evaluation in attenuating the fast-fed variability.

Bosutinib (BOS) is a BCS class IV drug that shows low oral bioavailability and high fast-fed variability. Various pharmaceutical formulations have been explored thus far in order to improve its bioavailability while avoiding fast-fed variability. In the present study, we explored cyclodextrin (CD) complexation strategy to overcome the aforementioned disadvantages associated with BOS. CD complexation is a simple, versatile and economic approach that enables formation of inclusion complexes, thereby improving aqueous solubility while nullifying pH-dependent solubility and fast-fed variability for poorly soluble drugs. Initially, we performed molecular dynamics and docking studies to select appropriate CD derivative. The results of in silico studies revealed that sulfo-butyl ether ß-cyclodextrin (SBE-CD) offered superior binding affinity with BOS. Further, Job's plot revealed that 1:1 stoichiometry of BOS and CD resulted in enhancement of BOS solubility up to ~ 132.6-folds. In vitro release studies in bio-relevant media (fasted and fed state simulated gastric and intestinal fluids) revealed higher drug release while overcoming its pH-dependent solubility. In vitro studies on K562 cells demonstrated a 1.83-fold enhancement in cytotoxicity due to enhanced ROS production and G2/M phase arrest.In vivo pharmacokinetic studies in Sprague-Dawley rats revealed insignificant fast-fed variability with AUCfast/fed 0.9493 and Cmaxfast/fed 0.8291 being closer to 1 in comparison with BOS. Hence, we conclude that SBE-CD complexation could be a promising approach in diminishing fast-fed variability of BOS.

Quality by design endorsed atorvastatin-loaded nanostructured lipid carriers embedded in pH-responsive gel for melanoma.

AIM: Our aim was to repurpose atorvastatin for melanoma by encapsulating in a nanostructured lipid carrier matrix to promote tumour cell internalisation and skin permeation. pH-responsive chitosan gel was employed to restrict At-NLCs in upper dermal layers. METHODS: We utilised a quality by design approach for encapsulating At within the NLC matrix. Further, cellular uptake and cytotoxicity was evaluated along with pH-responsive release and ex vivo skin permeation. RESULTS: Cytotoxicity assay showed 3.13-fold enhanced cytotoxicity on melanoma cells compared to plain drug with nuclear staining showing apoptotic markers. In vitro, release studies showed 5.9-fold rapid release in chitosan gel matrix at pH 5.5 compared to neutral pH. CONCLUSIONS: At-NLCs prevented precipitation, promoted skin permeation, and SK-MEL 28 cell internalisation. The localisation of NLCs on the upper dermal layer due to electrostatic interactions of skin with chitosan gel diminished the incidence of untoward systemic effects.

Supramolecular self-assembled peptide-engineered nanofibers: A propitious proposition for cancer therapy.

Cancer is a devastating disease that causes a substantial number of deaths worldwide. Current therapeutic interventions for cancer include chemotherapy, radiation therapy, or surgery. These conventional therapeutic approaches are associated with disadvantages such as multidrug resistance, destruction of healthy tissues, and tissue toxicity. Therefore, there is a paradigm shift in cancer management wherein nanomedicine-based novel therapeutic interventions are being explored to overcome the aforementioned disadvantages. Supramolecular self-assembled peptide nanofibers are emerging drug delivery vehicles that have gained much attention in cancer management owing to their biocompatibility, biodegradability, biomimetic property, stimuli-responsiveness, transformability, and inherent therapeutic property. Supramolecules form well-organized structures via non-covalent linkages, the intricate molecular arrangement helps to improve tissue permeation, pharmacokinetic profile and chemical stability of therapeutic agents while enabling targeted delivery and allowing efficient tumor imaging. In this review, we present fundamental aspects of peptide-based self-assembled nanofiber fabrication their applications in monotherapy/combinatorial chemo- and/or immuno-therapy to overcome multi-drug resistance. The role of self-assembled structures in targeted/stimuli-responsive (pH, enzyme and photo-responsive) drug delivery has been discussed along with the case studies. Further, recent advancements in peptide nanofibers in cancer diagnosis, imaging, gene therapy, and immune therapy along with regulatory obstacles towards clinical translation have been deliberated.

Biogenic synthesis of gold nanoparticles using dual extract of tulsi-Vinca for breast cancer tumor regression in mice.

Aim: This work aims to synthesize the gold nanoparticles (GNPs) using a dual extract of tulsi and Vinca (T+V-Gold) for breast cancer tumor regression. Methods: The GNPs were synthesized and characterized for their microscopic, spectroscopic and crystalline properties. Further, the GNPs were investigated for in vitro and in vivo studies for the treatment of the 4T1-induced triple-negative breast cancer murine model. Results: The GNPs for 4T1 tumor-challenged mice resulted in delayed tumor development and lower tumor burden, with T+V-Gold demonstrating the highest prevention of tumor spread. The antitumor effect of T+V-Gold is highly significant in the glutathione family antioxidants glutathione S-transferase and glutathione in tumor tissue samples. Conclusion: The bioefficacy and anticancer outcomes of T+V-Gold nanoformulation can be used as therapeutic agents and drug-delivery vehicles.

A silicon photomultiplier based compact gamma spectrometer for environmental gamma radiation monitoring networks.

In this paper, the details of the development and performance characterisation of a compact, low-power gamma spectrometer for environmental gamma radiation monitoring networks are presented. To reduce the power consumption and the size of the spectrometer, a gamma detector comprising a silicon photomultiplier coupled to a Gd3Ga3Al2O12:Ce,B (GGAG:Ce,B) scintillator has been used for gamma spectrometry. Initially, a Monte Carlo simulation study was carried out to verify the suitability of the 5 mm × 5 mm × 5 mm GGAG:Ce,B crystal for spectrometry of gamma sources in the energy range 60-1332 keV. For minimising the power consumption, the signal processing electronics has been custom designed. This electronics was realised using standard off-the-shelf components to reduce the cost. The developed spectrometer is of size 16 cm × 10 cm × 6 cm, weighs 600 g and consumes 600 mW power. The spectrometer is developed such that it could be directly interfaced with GSM/Xbee for wireless communication with the radiation monitoring networks. The lower-level discriminator threshold of the system is 40 keV and the total electronic noise is <20 keV. The experimentally measured sensitivity of the spectrometer for 137Cs (662 keV) is 2.4 cps/µGy/h at 3.5 V overvoltage. The spectrometer offers excellent linearity over the measured energy range of 60-1332 keV and an energy resolution of ~10% for 662 keV gamma-ray at room temperature.

Neutrophil membrane-based nanotherapeutics: Propitious paradigm shift in the management of cancer.

Cancer is the leading cause of death across the globe, with 19.3 million new cancer cases and 10 million deaths in the year 2020. Conventional treatment modalities have numerous pitfalls, such as off-site cytotoxicity and poor bioavailability. Nanocarriers (NCs) have been explored to deliver various therapeutic moieties such as chemotherapeutic agents and photothermal agents, etc. However, several limitations, such as rapid clearance by the reticuloendothelial system, poor extravasation into the tumor microenvironment, and low systemic half-life are roadblocks to successful clinical translation. To circumvent the pitfalls of currently available treatment modalities, neutrophil membrane (NM)-based nanotherapeutics have emerged as a promising platform for cancer management. Their versatile features such as natural tumor tropism, tumor-specific accumulation, and prevention from rapid clearance owing to their autologous nature make them an effective anticancer NCs. In this manuscript, we have discussed various methods for isolation, coating and characterization of NM. We have discussed the role of NM-coated nanotherapeutics as neoadjuvant and adjuvant in different treatment modalities, such as chemotherapy, photothermal and photodynamic therapies with rationales behind their inclusion. Clinical hurdles faced during the bench-to-bedside translation with possible solutions have been discussed. We believe that in the upcoming years, NM-coated nanotherapeutics will open a new horizon in cancer management.

3D printable, injectable amyloid-based composite hydrogel of bovine serum albumin and aloe vera for rapid diabetic wound healing.

Protein-based biomaterials, particularly amyloids, have sparked considerable scientific interest in recent years due to their exceptional mechanical strength, excellent biocompatibility and bioactivity. In this work, we have synthesized a novel amyloid-based composite hydrogel consisting of bovine serum albumin (BSA) and aloe vera (AV) gel to utilize the medicinal properties of the AV gel and circumvent its mechanical frangibility. The synthesized composite hydrogel demonstrated an excellent porous structure, self-fluorescence, non-toxicity, and controlled rheological properties. Moreover, this hydrogel possesses inherent antioxidant and antibacterial properties, which accelerate the rapid healing of wounds. The in vitro wound healing capabilities of the synthesized composite hydrogel were evaluated using 3T3 fibroblast cells. Moreover, the efficacy of the hydrogel in accelerating chronic wound healing via collagen crosslinking was investigated through in vivo experiments using a diabetic mouse skin model. The findings indicate that the composite hydrogel, when applied, promotes wound healing by inducing collagen deposition and upregulating the expression of vascular endothelial growth factor (VEGF) and its receptors. We also demonstrate the feasibility of the 3D printing of the BSA-AV hydrogel, which can be tailored to treat various types of wound. The 3D printed hydrogel exhibits excellent shape fidelity and mechanical properties that can be utilized for personalized treatment and rapid chronic wound healing. Taken together, the BSA-AV hydrogel has great potential as a bio-ink in tissue engineering as a dermal substitute for customizable skin regeneration.