Gold nanoparticles and gold nanorods in the landscape of cancer therapy.

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

Harnessing the Power of Stimuli-Responsive Nanoparticles as an Effective Therapeutic Drug Delivery System.

The quest for effective and reliable methods of delivering medications, with the aim of improving delivery of therapeutic agent to the intended location, has presented a demanding yet captivating field in biomedical research. The concept of smart drug delivery systems is an evolving therapeutic approach, serving as a model for directing drugs to specific targets or sites. These systems have been developed to specifically target and regulate the administration of therapeutic substances in a diverse array of chronic conditions, including periodontitis, diabetes, cardiac diseases, inflammatory bowel diseases, rheumatoid arthritis, and different cancers. Nevertheless, numerous comprehensive clinical trials are still required to ascertain both the immediate and enduring impacts of such nanosystems on human subjects. This review delves into the benefits of different drug delivery vehicles, aiming to enhance comprehension of their applicability in addressing present medical requirements. Additionally, it touches upon the current applications of these stimuli-reactive nanosystems in biomedicine and outlines future development prospects.

Recent advancement on albumin nanoparticles in treating lung carcinoma.

With the advancement of nanotechnology, many different forms of nanoparticles (NPs) are created, which specifically enhance anticancer drug delivery to tumour cells. Albumin bio-macromolecule is a flexible protein carrier for the delivery of drugs that is biodegradable, biocompatible, and non-toxic. As a result, it presents itself as an ideal material for developing nanoparticles for anticancer drug delivery. Toxicological investigations demonstrated that this novel drug delivery technique is safe for use in the human population. Furthermore, drug compatibility with the albumin nanoparticle is remarkable. The robust structure of the nanoparticle, high drug encapsulation, and customisable drug release make it a promising carrier option for the treatment of lung cancer. In this review, we summarise human serum albumin and bovine serum albumin in the targeted delivery of anticancer drugs to lung cancer cells.

Advancements in Polymeric Nanocarriers to Mediate Targeted Therapy against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a destructive disease with a poor prognosis, low survival rate and high rate of metastasis. It comprises 15% of total breast cancers and is marked by deficiency of three important receptor expressions, i.e., progesterone, estrogen, and human epidermal growth factor receptors. This absence of receptors is the foremost cause of current TNBC therapy failure, resulting in poor therapeutic response in patients. Polymeric nanoparticles are gaining much popularity for transporting chemotherapeutics, genes, and small-interfering RNAs. Due to their exclusive properties such as great stability, easy surface modification, stimuli-responsive and controlled drug release, ability to condense more than one therapeutic moiety inside, tumor-specific delivery of payload, enhanced permeation and retention effect, present them as ideal nanocarriers for increasing efficacy, bioavailability and reducing the toxicity of therapeutic agents. They can even be used as theragnostic agents for the diagnosis of TNBC along with its treatment. In this review, we discuss the limitations of already existing TNBC therapies and highlight the novel approach to designing and the functionalization of polymeric nanocarriers for the effective treatment of TNBC.

Itraconazole and Difluorinated-Curcumin Containing Chitosan Nanoparticle Loaded Hydrogel for Amelioration of Onychomycosis.

Onychomycosis is a nail infection caused by a fungus, Trichophyton mentagrophytes, that is responsible for major nail infections. The best method suited for treating such infections generally includes a topical remedy. However, conventional oral or topical formulations are associated with various limitations. Therefore, a more efficient and compatible formulation is developed in this study. The primary objective of the current study is to formulate and evaluate chitosan nanoparticle-based hydrogel for ameliorating onychomycosis. The sole purpose of this research was to increase the permeation of the lipophilic drug itraconazole and difluorinated curcumin, and its synergistic antifungal activity was also evaluated for the first time. Both in vitro and ex vivo drug release evaluations confirmed the sustained release of both drugs from the hydrogel, which is a prerequisite for treating onychomycosis. The results overall highlighted the promising activity of a synergistic approach that could be implemented for the treatment of onychomycosis. The hydrogel-based formulation serves as an effective method of delivery of drugs across the layers of the skin, resulting from its hydrating characteristics.

Advancement of cell-penetrating peptides in combating triple-negative breast cancer.

Extensive research efforts have been made and are still ongoing in the search for an ideal anti-cancer therapy. Almost all chemotherapeutics require a carrier or vehicle, a drug delivery system that can transport the drug specifically to the targeted cancer cells, sparing normal cells. Cell-penetrating peptides (CPPs) provide an effective and efficient pathway for the intra-cellular transportation of various bioactive molecules in several biomedical therapies. They are now well-recognized as facilitators of intracellular cargo delivery and have excellent potential for targeted anti-cancer therapy. In this review, we explain CPPs, recent progress in the development of new CPPs, and their utilization to transport cargoes such as imaging agents, chemotherapeutics, and short-interfering RNAs (siRNA) into tumor cells, contributing to the advancement of novel tumor-specific delivery systems.

Recent Update on the Alzheimer's Disease Progression, Diagnosis and Treatment Approaches.

Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disorder, manifested by the loss of memory and cognitive abilities, behavioral disturbance and progressive impairment of activities of daily life. The sharp rise in the number of AD patients has brought it within the top eight health issues in the world. It is associated with the distribution of misfolded aggregates of protein within the brain. However, Alois Alzheimer initially mentioned that the reduction in brain volume in AD might be associated with the "deposition of a special substance in the cortex". The resulting plaque found in extracellular space in the AD brain and hippocampus region, known as senile plaques, is the characteristic feature underlying Alzheimer's pathology, where the role of amyloid- ß (Aß) peptide formation from proteolytic cleavage of amyloid precursor protein (APP) by secretase enzyme is eminent. Therefore, this review has highlighted the molecular pathophysiology of AD with a variety of available diagnostic and treatment strategies for the management of the disease, with a focus on the advancement toward clinical research to provide new effective and safe tool in the diagnosis, treatment or management of AD.

Current Insight into the Therapeutic Potential of Phytocompounds and their Nanoparticle-Based Systems for Effective Management of Lung Cancer.

Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At present, various treatment approaches are available, such as chemotherapy, surgery, and radiotherapy, but all these approaches usually cause serious side effects like degeneration of normal cells, bone marrow depression, alopecia, extensive vomiting, etc. To overcome the aforementioned problems, researchers have focused on the alternative therapeutic approach in which various natural compounds are reported, which possessed anti-lung cancer activity. Phytocompounds exhibit their anti lung cancer activity via targeting various cell-signaling pathways, apoptosis and cell cycle arrest, and by regulating antioxidant status and detoxification. Apart from the excellent anti-cancer activity, clinical administration of phytocompounds is confined because of their high lipophilicity and low bioavailability. Therefore, researchers show their concern in the development of a stable, safe and effective approach of treatment with minimal side effects by the development of nanoparticle-based delivery of these phytocompounds to the target site. Targeted delivery of phytocompound through nanoparticles overcomes the aforementioned problems. In this article, the molecular mechanism of phytocompounds, their emerging combination therapy, and their nanoparticles-based delivery systems in the treatment of lung cancer have been discussed.

In Silico Drug Screening Based Development of Novel Formulations for Onychomycosis Management.

Onychomycosis is a prominent fungal infection that causes discoloration, thickening, and mutilation leading to the separation of the nail from the nail bed. Treatment modalities for onychomycosis may include oral, topical, or combination therapy with antifungals and at times may require chemical or surgical intervention. The burden of side effects of antifungals is enormous, and therefore using molecular docking-based drug selection in context with the target keratin protein would ensure better disease management. Ciclopirox, Amorolfine HCl, Efinaconazole, Tioconazole, and Tavaborole were submitted for assessment, revealing that Amorolfine HCl is the best fit. Consequently, two formulations (Nail lacquer and nanoemulgel) were developed from Amorolfine HCl to validate the in silico screening outcomes. The formulations were further fortified with over-the-counter ingredients vis-a-vis with vitamin E in nail lacquer and undecylenic acid in nanoemulgel for their prominent roles in improving nail health. Both the formulations were systematically designed, optimized, and characterized. Amorolfine HCl containing nanoemulgel (NEG) was developed using undecylenic acid as an oil phase and thioglycolic acid as a penetration enhancer. The quality parameters evaluated were particle size, the zeta potential for nanoemulsion (NE) (78.04 ± 4.724 nm and -0.7mV, respectively), in vitro cumulative drug release (96.74% for NE and 88.54% for NEG), and transungual permeation (about 73.49% for NEG and 54.81% for NE). Nail lacquer was evaluated for the drying time, non-volatile content, and blush test. In vitro cumulative drug release of the developed nail lacquer and comparator marketed formulations were around 81.5% and 75%, respectively. Similarly, the transungual drug permeation was 6.32 µg/cm2 and 5.89 µg/cm2, respectively, in 24 h. The in silico guided preparation of both formulations containing Amorolfine HCl and over the counter ingredients is amenable for therapeutic use against onychomycosis and will be evaluated in the in vivo model.

Recombinant deoxyribonucleoside kinase from Drosophila melanogaster can improve gemcitabine based combined gene/chemotherapy for targeting cancer cells.

A recombinant deoxyribonucleoside kinase from Drosophila melanogaster with a deletion of the last 20 amino acid residues (named DmdNKΔC20) was hypothesized as a potential therapeutic tool for gene therapy due to its broad substrate specificity and better catalytic efficiency towards nucleosides and nucleoside analogs. This study was designed to evaluate the effect of DmdNKΔC20 for sensitizing human cancer cell lines to gemcitabine and to further investigate its role in reversal of acquired drug resistance in gemcitabine-resistant cancer cell line. The DmdNKΔC20 gene was delivered to three different cancer cell lines, including breast, colon and liver cancer cells, using lipid-mediated transfection reagent. After transfection, gene expression of DmdNKΔC20 was confirmed by quantitative reverse transcription PCR (qRT-PCR) and the combined effect of DmdNKΔC20 and gemcitabine based cytotoxicity was observed by cell viability assay. We further evolved a gemcitabine-resistant breast cancer cell line (named MCF7-R) through directed evolution in the laboratory, which showed 375-fold more resistance compared with parental MCF7 cells. Upon transfection with DmdNKΔC20 gene, MCF7-R cells showed 83-fold higher sensitivity to gemcitabine compared with the control group of MCF7-R cells. Moreover, we observed 79% higher expression of p21 protein in transfected MCF7-R cells, which may indicate induction of apoptosis. Our findings highlight the importance and therapeutic potential of DmdNKΔC20 in combined gene/chemotherapy approach to target a wide range of cancers, particularly gemcitabine-resistant cancers.