Impacts of oxidative stress and anti-oxidants on the development, pathogenesis, and therapy of sickle cell disease: A comprehensive review.

Sickle cell disease (SCD) is the most severe monogenic hemoglobinopathy caused by a single genetic mutation that leads to repeated polymerization and depolymerization of hemoglobin resulting in intravascular hemolysis, cell adhesion, vascular occlusion, and ischemia-reperfusion injury. Hemolysis causes oxidative damage indirectly by generating reactive oxygen species through various pathophysiological mechanisms, which include hemoglobin autoxidation, endothelial nitric oxide synthase uncoupling, reduced nitric oxide bioavailability, and elevated levels of asymmetric dimethylarginine. Red blood cells have a built-in anti-oxidant system that includes enzymes like sodium dismutase, catalase, and glutathione peroxidase, along with free radical scavenging molecules, such as vitamin C, vitamin E, and glutathione, which help them to fight oxidative damage. However, these anti-oxidants may not be sufficient to prevent the effects of oxidative stress in SCD patients. Therefore, in line with a recent FDA request that the focus to be placed on the development of innovative therapies for SCD that address the root cause of the disease, there is a need for therapies that target oxidative stress and restore redox balance in SCD patients. This review summarizes the current state of knowledge regarding the role of oxidative stress in SCD and the potential benefits of anti-oxidant therapies. It also discusses the challenges and limitations of these therapies and suggests future directions for research and development.

Advances in biomedical applications of vitamin D for VDR targeted management of obesity and cancer.

BACKGROUND: 1,25(OH)2D3 is a fat-soluble vitamin, involved in regulating Ca2+ homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is the result of abnormal lipid deposition due to the prolonged positive energy balance and increases the risk of several cancer types. Furthermore, it has been associated with vitamin D deficiency and defined as a low 25(OH)2D3 blood level. In addition, 1,25(OH)2D3 plays vital roles in Ca2+-Pi and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes. SCOPE AND APPROACH: The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH)2D3-deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery. KEY FINDINGS AND CONCLUSIONS: Several studies have revealed that cancer development in a background of 1,25(OH)2D3 deficient obesity involves the VDR gene. Moreover, 1,25(OH)2D3 is also known to influence several cellular processes, including differentiation, proliferation, and adhesion. The multifaceted physiology of obesity has improved our understanding of the cancer therapeutic targets. However, currently available anti-cancer drugs are notorious for their side effects, which have raised safety issues. Thus, there is interest in developing 1,25(OH)2D3-based therapies without any side effects.

The role of NF-κB in breast cancer initiation, growth, metastasis, and resistance to chemotherapy.

Breast cancer (BC) is the second most fatal disease and is the prime cause of cancer allied female deaths. BC is caused by aberrant tumor suppressor genes and oncogenes regulated by transcription factors (TFs) like NF-κB. NF-κB is a pro-inflammatory TF that crucially alters the expressions of various genes associated with inflammation, cell progression, metastasis, and apoptosis and modulates a network of genes that underlie tumorigenesis. Herein, we focus on NF-κB signaling pathways, its regulators, and the rationale for targeting NF-κB. This review also includes TFs that maintain NF-κB crosstalk and their roles in promoting angiogenesis and metastasis. In addition, we discuss the importance of combination therapies, resistance to treatment, and potential novel therapeutic strategies including nanomedicine that targets NF-κB.

HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer.

HOX transcript antisense intergenic RNA (HOTAIR) is an oncogenic non-coding RNA whose expression is strongly correlated with the tumor grade and prognosis of a variety of carcinomas including breast cancer (BC). HOTAIR regulates various target genes via sponging and epigenetic mechanisms and controls various oncogenic cellular and signaling mechanisms including metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by a variety of transcriptional and epigenetic mechanisms. In this review, we describe the regulatory mechanisms that govern HOTAIR expression during cancer development and explore how HOTAIR drives BC development, metastasis, and drug resistance. In the final section of this review, we focus on the role of HOTAIR in BC management, therapeutic treatment, and prognosis, highlighting its potential therapeutic applications.

A Novel and Cost-Effective CsVO3 Quantum Dots for Optoelectronic and Display Applications.

Quantum dots (QDs) have an unparalleled ability to mimic true colors due to their size-tunable optical and electronic properties, which make them the most promising nanoparticles in various fields. Currently, the majority of QDs available in the market are cadmium, indium, and lead-based materials but the toxicity and unstable nature of these QDs restricts their industrial and practical applications. To avoid using heavy metal ions, especially cadmium, the current research is focused on the fabrication of perovskite and vanadate QDs. Herein, we report the facile synthesis of a novel and cost-effective CsVO3 QDs for the first time. The sizes of the CsVO3 QDs produced were tuned from 2 to 10 nm by varying the reaction temperature from 140 to 190 °C. On increasing QD size, a continuous red shift was observed in absorption and emission spectra, signifying the presence of quantum confinement. In addition, along with CsVO3 QDs, the CsVO3 nanosheets self-assembled microflower-like particles were found as residue after the centrifugation; the X-ray diffraction indicated an orthorhombic structure. Under 365 nm excitation, these CsVO3 microflower-like particles exhibited broad emission with CIE coordinates in the white emission region. The acquired results suggest that CsVO3 QDs may represent a new class of cadmium-free materials for optoelectronic and biomedical applications.

Evolution of Highly Biocompatible and Thermally Stable YVO4:Er3+/Yb3+ Upconversion Mesoporous Hollow Nanospheriods as Drug Carriers for Therapeutic Applications.

In recent times, upconversion nanomaterials with mesoporous hollow structures have gained significant interest as a prospective nano-platform for cancer imaging and therapeutic applications. In this study, we report a highly biocompatible YVO4:1Er3+/10Yb3+ upconversion mesoporous hollow nanospheriods (YVO4:Er3+/Yb3+ UC-MHNSPs) by a facile and rapid self-sacrificing template method. The Rietveld analysis confirmed their pure phase of tetragonal zircon structure. Nitrogen adsorption-desorption isotherms revealed the mesoporous nature of these UC-MHNSPs and the surface area is found to be ~87.46 m2/g. Under near-infrared excitation (980 nm), YVO4:Er3+/Yb3+ UC-MHNSPs showed interesting color tunability from red to green emission. Initially (at 0.4 W), energy back transfer from Er3+ to Yb3+ ions leads to the strong red emission. Whereas at high pump powers (1 W), a fine green emission is observed due to the dominant three-photon excitation process and traditional energy transfer route from Er3+ to Yb3+ ions. The bright red light from the membrane of HeLa cells confirmed the effective cellular uptake of YVO4:Er3+/Yb3+ UC-MHNSPs. The resonant decrease in cell viability on increasing the concentration of curcumin conjugated YVO4:Er3+/Yb3+ UC-MHNSPs established their excellent antitumor activity. Therefore, the acquired results indicate that these YVO4:Er3+/Yb3+ UC-MHNSPs are promising drug carriers for bioimaging and various therapeutic applications.

Nanoparticles mediated tumor microenvironment modulation: current advances and applications.

The tumor microenvironment (TME) plays a key role in cancer development and emergence of drug resistance. TME modulation has recently garnered attention as a potential approach for reprogramming the TME and resensitizing resistant neoplastic niches to existing cancer therapies such as immunotherapy or chemotherapy. Nano-based solutions have important advantages over traditional platform and can be specifically targeted and delivered to desired sites. This review explores novel nano-based approaches aimed at targeting and reprogramming aberrant TME components such as macrophages, fibroblasts, tumor vasculature, hypoxia and ROS pathways. We also discuss how nanoplatforms can be combined with existing anti-tumor regimens such as radiotherapy, immunotherapy, phototherapy or chemotherapy to enhance clinical outcomes in solid tumors.

Engineered nanoparticles for imaging and drug delivery in colorectal cancer.

Colorectal cancer (CRC) is one of the deadliest diseases worldwide due to a lack of early detection methods and appropriate drug delivery strategies. Conventional imaging techniques cannot accurately distinguish benign from malignant tissue, leading to frequent misdiagnosis or diagnosis at late stages of the disease. Novel screening tools with improved accuracy and diagnostic precision are thus required to reduce the mortality burden of this malignancy. Additionally, current therapeutic strategies, including radio- and chemotherapies carry adverse side effects and are limited by the development of drug resistance. Recent advances in nanotechnology have rendered it an attractive approach for designing novel clinical solutions for CRC. Nanoparticle-based formulations could assist early tumor detection and help to overcome the limitations of conventional therapies including poor aqueous solubility, nonspecific biodistribution and limited bioavailability. In this review, we shed light on various types of nanoparticles used for diagnosis and drug delivery in CRC. In addition, we will explore how these nanoparticles can improve diagnostic accuracy and promote selective drug targeting to tumor sites with increased efficiency and reduced cytotoxicity against healthy colon tissue.

Nanomaterials multifunctional behavior for enlightened cancer therapeutics.

Cancer is an outrageous disease with uncontrolled differentiation, growth, and migration to the other parts of the body. It is the second-most common cause of death both in the U.S. and worldwide. Current conventional therapies, though much improved and with better prognosis, have several limitations. Chemotherapeutic agents, for instance, are cytotoxic to both tumor and healthy cells, and the non-specific distribution of drugs at tumor sites limits the dose administered. Nanotechnology, which evolved from the coalescence and union of varied scientific disciplines, is a novel science that has been the focus of much research. This technology is generating more effective cancer therapies to overcome biomedical and biophysical barriers against standard interventions in the body; its unique magnetic, electrical, and structural properties make it a promising tool. This article reviews endogenous- and exogenous-based stimulus-responsive drug delivery systems designed to overcome the limitations of conventional therapies. The article also summarizes the study of nanomaterials, including polymeric, gold, silver, magnetic, and quantum dot nanoparticles. Though an array of drug delivery systems has so far been proposed, there remain many challenges and concerns that should be addressed in order to fill the gaps in the field. Prominence is given to drug delivery systems that employ external- and internal-based stimuli and that are emerging as promising tools for cancer therapeutics in clinical settings.

Horizons of nanotechnology applications in female specific cancers.

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.

Folate-conjugated nanovehicles: Strategies for cancer therapy.

Cancer theranostics represents a strategy that aims at combining diagnosis with therapy through the simultaneous imaging and targeted delivery of therapeutics to cancer cells. Recently, the folate receptor alpha has emerged as an attractive theranostic target due to its overexpression in multiple solid tumors and its great functional versatility. In fact, it can be incorporated into folate-conjugated nano-systems for imaging and drug delivery. Hence, it can be used along the line of personalized clinical strategies as both an imaging tool and a delivery method ensuring the selective transport of treatments to tumor cells, thus highlighting its theranostic qualities. In this review, we will explore these theranostic characteristics in detail and assess their clinical potential. We will also discuss the technological advances that have allowed the design of sophisticated folate-based nanocarriers harboring various chemical properties and suited for the transport of various therapeutic agents.

Folate-targeted immunotherapies: Passive and active strategies for cancer.

The glycoprotein FRα is a membrane-attached transport protein that is shielded from the immune system in healthy cells. However, it is upregulated in various malignancies, involved in cancer development and is also immunogenic. Furthermore, FRα is a tumor-associated antigen endowed with unique properties, thus rendering it a suitable target for immunotherapeutic development in cancer. Various anti- FRα immunotherapeutic strategies are thus currently being developed and clinically assessed for the treatment of various solid tumors. These approaches include passive anti-FRα immunotherapies, such as monoclonal antibodies, or active immunotherapies, such as CART, folate haptens and vaccines. In this review, we will explore the advances in the field of FRα-based immune therapies and discuss both their successes and shortcomings in the clinical setting.