Cancer Nanovaccines: Nanomaterials and Clinical Perspectives.

Cancer nanovaccines represent a promising frontier in cancer immunotherapy, utilizing nanotechnology to augment traditional vaccine efficacy. This review comprehensively examines the current state-of-the-art in cancer nanovaccine development, elucidating innovative strategies and technologies employed in their design. It explores both preclinical and clinical advancements, emphasizing key studies demonstrating their potential to elicit robust anti-tumor immune responses. The study encompasses various facets, including integrating biomaterial-based nanocarriers for antigen delivery, adjuvant selection, and the impact of nanoscale properties on vaccine performance. Detailed insights into the complex interplay between the tumor microenvironment and nanovaccine responses are provided, highlighting challenges and opportunities in optimizing therapeutic outcomes. Additionally, the study presents a thorough analysis of ongoing clinical trials, presenting a snapshot of the current clinical landscape. By curating the latest scientific findings and clinical developments, this study aims to serve as a comprehensive resource for researchers and clinicians engaged in advancing cancer immunotherapy. Integrating nanotechnology into vaccine design holds immense promise for revolutionizing cancer treatment paradigms, and this review provides a timely update on the evolving landscape of cancer nanovaccines.

Targeted therapies for HPV-associated cervical cancer: Harnessing the potential of exosome-based chipsets in combating leukemia and HPV-mediated cervical cancer.

Exosomes play a crucial role in intercellular communication and have emerged as significant vehicles for transporting disease-specific biomarkers. This feature provides profound insights into the progression of diseases and the responses of patients to treatments. For example, in leukemia, exosomes convey critical information through the carriage of specific proteins and nucleic acids. In the case of human papillomavirus (HPV)-mediated cervical cancer, exosomes are particularly useful for noninvasive detection as they transport high-risk HPV DNA and specific biomolecules, which can be indicators of the disease. Despite their vast potential, there are several challenges associated with the use of exosomes in medical diagnostics. These include their inherent heterogeneity, the need for enhanced sensitivity in detection methods, the establishment of standardization protocols, and the requirement for cost-effective scalability in their application. Addressing these challenges is crucial for the effective implementation of exosome-based diagnostics. Future research and development are geared towards overcoming these obstacles. Efforts are concentrated on refining the processes of biomarker discovery, establishing comprehensive regulatory frameworks, developing convenient point-of-care devices, exploring methods for multimodal detection, and conducting extensive clinical trials. The ultimate goal of these efforts is to inaugurate a new era of precision diagnostics within healthcare. This would significantly improve patient outcomes and reduce the burden of diseases such as leukemia and HPV-mediated cervical cancer. The integration of exosomes with cutting-edge technology holds the promise of significantly reinforcing the foundations of healthcare, leading to enhanced diagnostic accuracy, better disease monitoring, and more personalized therapeutic approaches.

Chitosan lecithin nanocomposite based electrochemical biosensor for glycine detection in biological matrices.

Increased glycine concentrations are associated with altered metabolism of cancer cells and is reflected in the bodily fluids of the brain cancer patients. Various studies have been conducted in past to detect glycine as an imaging biomarker via NMR Spectroscopy tools. However, the use is limited because of the low concentration and different in vivo detection due to overlapping of peaks with myo-inositol in same spectral position. Alongside, little is known about the electrochemical potential of Glycine as a biomarker for brain cancer. The prime impetus of this study was to check the feasibility of glycine as non-invasive biomarker for brain cancer. A divergent approach to detect glycine "non-enzymatically" via unique chitosan lecithin nanocomposite has been utilised during this study. The electrochemical inactivity at provided potential that prevented glycine to get oxidized or reduced without mediator was compensated utilising the chitosan-lecithin nanocomposite. Thus, a redox mediator (Prussian blue) was used for high sensitivity and indirect detection of glycine. The chitosan nanoparticles-lecithin nanocomposite is used as a matrix. The electrochemical analysis of the onco-metabolomic biomarker (glycine) utilizing cyclic voltammetry in glycine spiked multi-Purpose artificial urine was performed to check distribution of glycine over physiological range of glycine. A wide linear range of response varying over the physiological range from 7 to 240 µM with a LOD 8.5 µM was obtained, showing potential of detection in biological samples. We have further evaluated our results via simulating the interaction of mediator and matrix with Glycine by HOMO-LUMO band fluctuations.

Revolutionizing Cancer Treatment: The Promising Horizon of Zein Nanosystems.

Various nanomaterials have recently become fascinating tools in cancer diagnostic applications because of their multifunctional and inherent molecular characteristics that support efficient diagnosis and image-guided therapy. Zein nanoparticles are a protein derived from maize. It belongs to the class of prolamins possessing a spherical structure with conformational properties similar to those of conventional globular proteins like ribonuclease and insulin. Zein nanoparticles have gained massive interest over the past couple of years owing to their natural hydrophilicity, ease of functionalization, biodegradability, and biocompatibility, thereby improving oral bioavailability, nanoparticle targeting, and prolonged drug administration. Thus, zein nanoparticles are becoming a promising candidate for precision cancer drug delivery. This review highlights the clinical significance of applying zein nanosystems for cancer theragnostic─moreover, the role of zein nanosystems for cancer drug delivery, anticancer agents, and gene therapy. Finally, the difficulties and potential uses of these NPs in cancer treatment and detection are discussed. This review will pave the way for researchers to develop theranostic strategies for precision medicine utilizing zein nanosystems.

Role of Exosomes in Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is a fundamental process driving cancer metastasis, transforming non-motile cells into a motile population that migrates to distant organs and forms secondary tumors. In recent years, cancer research has revealed a strong connection between exosomes and the EMT. Exosomes, a subpopulation of extracellular vesicles, facilitate cellular communication and dynamically regulate various aspects of cancer metastasis, including immune cell suppression, extracellular matrix remodeling, metastasis initiation, EMT initiation, and organ-specific metastasis. Tumor-derived exosomes (TEXs) and their molecular cargo, comprising proteins, lipids, nucleic acids, and carbohydrates, are essential components that promote EMT in cancer. TEXs miRNAs play a crucial role in reprogramming the tumor microenvironment, while TEX surface integrins contribute to organ-specific metastasis. Exosome-based cancer metastasis research offers a deeper understanding about cancer and an effective theranostic platform development. Additionally, various therapeutic sources of exosomes are paving the way for innovative cancer treatment development. In this Review, we spotlight the role of exosomes in EMT and their theranostic impact, aiming to inspire cancer researchers worldwide to explore this fascinating field in more innovative ways.

Unlocking Exosome-Based Theragnostic Signatures: Deciphering Secrets of Ovarian Cancer Metastasis.

Ovarian cancer (OC) is a common gynecological cancer worldwide. Unfortunately, the lack of early detection methods translates into a substantial cohort of women grappling with the pressing health crisis. The discovery of extracellular vesicles (EVs) (their major subpopulation exosomes, microvesicles, and apoptotic bodies) has provided new insights into the understanding of cancer. Exosomes, a subpopulation of EVs, play a crucial role in cellular communication and reflect the cellular status under both healthy and pathological conditions. Tumor-derived exosomes (TEXs) dynamically influence ovarian cancer progression by regulating uncontrolled cell growth, immune suppression, angiogenesis, metastasis, and the development of drug and therapeutic resistance. In the field of OC diagnostics, TEXs offer potential biomarkers in various body fluids. On the other hand, exosomes have also shown promising abilities to cure ovarian cancer. In this review, we address the interlink between exosomes and ovarian cancer and explore their theragnostic signature. Finally, we highlight future directions of exosome-based ovarian cancer research.

Revolutionizing Human papillomavirus (HPV)-related cancer therapies: Unveiling the promise of Proteolysis Targeting Chimeras (PROTACs) and Proteolysis Targeting Antibodies (PROTABs) in cancer nano-vaccines.

Personalized cancer immunotherapies, combined with nanotechnology (nano-vaccines), are revolutionizing cancer treatment strategies, explicitly targeting Human papilloma virus (HPV)-related cancers. Despite the availability of preventive vaccines, HPV-related cancers remain a global concern. Personalized cancer nano-vaccines, tailored to an individual's tumor genetic mutations, offer a unique and promising solution. Nanotechnology plays a critical role in these vaccines by efficiently delivering tumor-specific antigens, enhancing immune responses, and paving the way for precise and targeted therapies. Recent advancements in preclinical models have demonstrated the potential of polymeric nanoparticles and high-density lipoprotein-mimicking nano-discs in augmenting the efficacy of personalized cancer vaccines. However, challenges related to optimizing the nano-carrier system and ensuring safety in human trials persist. Excitingly, the integration of nanotechnology with Proteolysis-Targeting Chimeras (PROTACs) provides an additional avenue to enhance the effectiveness of personalized cancer treatment. PROTACs selectively degrade disease-causing proteins, amplifying the impact of nanotechnology-based therapies. Overcoming these challenges and leveraging the synergistic potential of nanotechnology, PROTACs, and Proteolysis-Targeting Antibodies hold great promise in pursuing novel and effective therapeutic solutions for individuals affected by HPV-related cancers.

Functionalized manganese iron oxide nanoparticles: a dual potential magneto-chemotherapeutic cargo in a 3D breast cancer model.

Localized heat generation from manganese iron oxide nanoparticles (MIONPs) conjugated with chemotherapeutics under the exposure of an alternating magnetic field (magneto-chemotherapy) can revolutionize targeted breast cancer therapy. On the other hand, the lack of precise control of local temperature and adequate MIONP distribution in laboratory settings using the conventional two-dimensional (2D) cellular models has limited its further translation in tumor sites. Our current study explored advanced 3D in vitro tumor models as a promising alternative to replicate the complete range of tumor characteristics. Specifically, we have focused on investigating the effectiveness of MIONP-based magneto-chemotherapy (MCT) as an anticancer treatment in a 3D breast cancer model. To achieve this, chitosan-coated MIONPs (CS-MIONPs) are synthesized and functionalized with an anticancer drug (doxorubicin) and a tumor-targeting aptamer (AS1411). CS-MIONPs with a crystallite size of 16.88 nm and a specific absorption rate (SAR) of 181.48 W g-1 are reported. In vitro assessment of MCF-7 breast cancer cell lines in 2D and 3D cell cultures demonstrated anticancer activity. In the 2D and 3D cancer models, the MIONP-mediated MCT reduced cancer cell viability to about 71.48% and 92.2%, respectively. On the other hand, MIONP-mediated MCT under an AC magnetic field diminished spheroids' viability to 83.76 ± 2%, being the most promising therapeutic modality against breast cancer.

Advancement in Biopolymer Assisted Cancer Theranostics.

Applications of nanotechnology have increased the importance of research and nanocarriers, which have revolutionized the method of drug delivery to treat several diseases, including cancer, in the past few years. Cancer, one of the world's fatal diseases, has drawn scientists' attention for its multidrug resistance to various chemotherapeutic drugs. To minimize the side effects of chemotherapeutic agents on healthy cells and to develop technological advancement in drug delivery systems, scientists have developed an alternative approach to delivering chemotherapeutic drugs at the targeted site by integrating it inside the nanocarriers like synthetic polymers, nanotubes, micelles, dendrimers, magnetic nanoparticles, quantum dots (QDs), lipid nanoparticles, nano-biopolymeric substances, etc., which has shown promising results in both preclinical and clinical trials of cancer management. Besides that, nanocarriers, especially biopolymeric nanoparticles, have received much attention from researchers due to their cost-effectiveness, biodegradability, treatment efficacy, and ability to target drug delivery by crossing the blood-brain barrier. This review emphasizes the fabrication processes, the therapeutic and theragnostic applications, and the importance of different biopolymeric nanocarriers in targeting cancer both in vitro and in vivo, which conclude with the challenges and opportunities of future exploration using biopolymeric nanocarriers in onco-therapy with improved availability and reduced toxicity.

Raman Spectroscopy: A Tool for Molecular Fingerprinting of Brain Cancer.

Brain cancer is one of those few cancers with very high mortality and low five-year survival rate. First and foremost reason for the woes is the difficulty in diagnosing and monitoring the progression of brain tumors both benign and malignant, noninvasively and in real time. This raises a need in this hour for a tool to diagnose the tumors in the earliest possible time frame. On the other hand, Raman spectroscopy which is well-known for its ability to precisely represent the molecular markers available in any sample given, including biological ones, with great sensitivity and specificity. This has led to a number of studies where Raman spectroscopy has been used in brain tumors in various ways. This review article highlights the fundamentals of Raman spectroscopy and its types including conventional Raman, SERS, SORS, SRS, CARS, etc. are used in brain tumors for diagnostics, monitoring, and even theragnostics, collating all the major works in the area. Also, the review explores how Raman spectroscopy can be even more effectively used in theragnostics and the clinical level which would make them a one-stop solution for all brain cancer needs in the future.

Photothermal therapy using graphene quantum dots.

The rapid development of powerful anti-oncology medicines have been possible because of advances in nanomedicine. Photothermal therapy (PTT) is a type of treatment wherein nanomaterials absorb the laser energy and convert it into localized heat, thereby causing apoptosis and tumor eradication. PTT is more precise, less hazardous, and easy-to-control in comparison to other interventions such as chemotherapy, photodynamic therapy, and radiation therapy. Over the past decade, various nanomaterials for PTT applications have been reviewed; however, a comprehensive study of graphene quantum dots (GQDs) has been scantly reported. GQDs have received huge attention in healthcare technologies owing to their various excellent properties, such as high water solubility, chemical stability, good biocompatibility, and low toxicity. Motivated by the fascinating scientific discoveries and promising contributions of GQDs to the field of biomedicine, we present a comprehensive overview of recent progress in GQDs for PTT. This review summarizes the properties and synthesis strategies of GQDs including top-down and bottom-up approaches followed by their applications in PTT (alone and in combination with other treatment modalities such as chemotherapy, photodynamic therapy, immunotherapy, and radiotherapy). Furthermore, we also focus on the systematic study of in vitro and in vivo toxicities of GQDs triggered by PTT. Moreover, an overview of PTT along with the synergetic application used with GQDs for tumor eradication are discussed in detail. Finally, directions, possibilities, and limitations are described to encourage more research, which will lead to new treatments and better health care and bring people closer to the peak of human well-being.

Clinical Theranostics Trademark of Exosome in Glioblastoma Metastasis.

Glioblastoma (GBM) is an aggressive type of cancer that has led to the death of a large population. The traditional approach fails to develop a solution for GBM's suffering life. Extensive research into tumor microenvironments (TME) indicates that TME extracellular vesicles (EVs) play a vital role in cancer development and progression. EVs are classified into microvacuoles, apoptotic bodies, and exosomes. Exosomes are the most highlighted domains in cancer research. GBM cell-derived exosomes participate in multiple cancer progression events such as immune suppression, angiogenesis, premetastatic niche formation (PMN), ECM (extracellular matrix), EMT (epithelial-to-mesenchymal transition), metastasis, cancer stem cell development and therapeutic and drug resistance. GBM exosomes also carry the signature of a glioblastoma-related status. The exosome-based GBM examination is part of the new generation of liquid biopsy. It also solved early diagnostic limitations in GBM. Traditional therapeutic approaches do not cross the blood-brain barrier (BBB). Exosomes are a game changer in GBM treatment and it is emerging as a potential platform for effective, efficient, and specific therapeutic development. In this review, we have explored the exosome-GBM interlink, the clinical impact of exosomes on GBM biomarkers, the therapeutics signature of exosomes in GBM, exosome-based research challenges, and future directions in GBM. Therefore, the GBM-derived exosomes offer unique therapeutic opportunities, which are currently under preclinical and clinical testing.

Antimicrobial and anti-biofilm activities of bio-inspired nanomaterials for wound healing applications.

Chronic wounds are ubiquitously inhabited by bacteria, and they remain a challenge as they cause significant discomfort and because their treatment consumes huge clinical resources. To reduce the burden that chronic wounds place upon both patients and health services, a wide variety of approaches have been devised and investigated. Bioinspired nanomaterials have shown great success in wound healing when compared to existing approaches, showing better ability to mimic natural extracellular matrix (ECM) components and thus to promote cell adhesion, proliferation, and differentiation. Wound dressings that are based on bioinspired nanomaterials can be engineered to promote anti-inflammatory mechanisms and to inhibit the formation of microbial biofilms. We consider the extensive potential of bioinspired nanomaterials in wound healing, revealing a scope beyond that covered previously.

Targeting the tumor microenvironment: Potential strategy for cancer therapeutics.

Cellular and stromal components including tumor cells, immune cells, mesenchymal cells, cancer-linked fibroblasts, and extracellular matrix, constituent tumor microenvironment (TME). TME plays a crucial role in reprogramming tumor initiation, uncontrolled proliferation, invasion and metastasis as well as response to therapeutic modalities. In recent years targeting the TME has developed as a potential strategy for treatment of cancer because of its life-threatening functions in restricting tumor development and modulating responses to standard-of-care medicines. Cold atmospheric plasma, oncolytic viral therapy, bacterial therapy, nano-vaccine, and repurposed pharmaceuticals with combination therapy, antiangiogenic drugs, and immunotherapies are among the most effective therapies directed by TME that have either been clinically authorized or are currently being studied. This article discusses above-mentioned therapies in light of targeting TME. We also cover problems related to the TME-targeted therapies, as well as future insights and practical uses in this rapidly growing field.

Promise of dostarlimab in cancer therapy: Advancements and cross-talk considerations.

In recent years, immunotherapy for cancer treatment using monoclonal antibodies has shown clinical success, particularly with programmed cell death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1). Dostarlimab, an immune checkpoint inhibitor, interacts with adaptive immunity by binding to human PD-1, inhibiting PD-L1 and PD-L2 interactions, and cross-talk with adaptive immunity. Recent clinical trials have shown that dostarlimab is effective in treating mismatch repair deficiency (dMMR) in endometrial cancer patients, leading to its approval in the United States and the European Union in 2021. This article provides a comprehensive overview of dostarlimab, its therapeutic ability, and the different indications for which it is being used. Dostarlimab could serve as a potential alternative to many cancer treatments that frequently have severe consequences on patients' quality of life.

Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics.

Exosomes are the phospholipid-membrane-bound subpopulation of extracellular vesicles derived from the plasma membrane. The main activity of exosomes is cellular communication. In cancer, exosomes play an important rolefrom two distinct perspectives, one related to carcinogenesis and the other as theragnostic and drug delivery tools. The outer phospholipid membrane of Exosome improves drug targeting efficiency. . Some of the vital features of exosomes such as biocompatibility, low toxicity, and low immunogenicity make it a more exciting drug delivery system. Exosome-based drug delivery is a new innovative approach to cancer treatment. Exosome-associated biomarker analysis heralded a new era of cancer diagnostics in a more specific way. This Review focuses on exosome biogenesis, sources, isolation, interrelationship with cancer and exosome-related cancer biomarkers, drug loading methods, exosome-based biomolecule delivery, advances and limitations of exosome-based drug delivery, and exosome-based drug delivery in clinical settings studies. The exosome-based understanding of cancer will change the diagnostic and therapeutic approach in the future.

Temozolomide Resistance: A Multifarious Review on Mechanisms Beyond O-6-Methylguanine-DNA Methyltransferase.

BACKGROUND: Chemotherapy with the oral alkylating agent temozolomide still prevails as a linchpin in the therapeutic regimen of glioblastoma alongside radiotherapy. Because of the impoverished prognosis and sparse chemotherapeutic medicaments associated with glioblastoma, the burgeoning resistance to temozolomide has made the whole condition almost irremediable. OBJECTIVE: The present review highlights the possible mechanisms of drug resistance following chemotherapy with temozolomide. METHODS: The review summarizes the recent developments, as published in articles from Scopus, PubMed, and Web of Science search engines. DESCRIPTION: One of the prime resistance mediators, O-6-methylguanine-DNA methyltransferase, upon activation, removes temozolomide-induced methyl adducts bound to DNA and reinstates genomic integrity. In the bargain, neoteric advances in the conception of temozolomide resistance have opened the door to explore several potential mediators like indirect DNA repair systems, efflux mechanisms, epigenetic modulation, microenvironmental influences, and autophagy-apoptosis processes that constantly lead to the failure of chemotherapy. CONCLUSION: This review sheds light on recent discoveries, proposed theories, and clinical developments in the field of temozolomide resistance to summarize the complex and intriguing involvement of oncobiological pathways.

Application of Mn x Fe1-x Fe2O4 (x = 0-1) Nanoparticles in Magnetic Fluid Hyperthermia: Correlation with Cation Distribution and Magnetostructural Properties.

Optimization of manganese-substituted iron oxide nanoferrites having the composition Mn x Fe1-x Fe2O4 (x = 0-1) has been achieved by the chemical co-precipitation method. The crystallite size and phase purity were analyzed from X-ray diffraction. With increases in Mn2+ concentration, the crystallite size varies from 5.78 to 9.94 nm. Transmission electron microscopy (TEM) analysis depicted particle sizes ranging from 10 ± 0.2 to 13 ± 0.2 nm with increasing Mn2+ substitution. The magnetization (M s) value varies significantly with increasing Mn2+ substitution. The variation in the magnetic properties may be attributed to the substitution of Fe2+ ions by Mn2+ ions inducing a change in the superexchange interaction between the A and B sublattices. The self-heating characteristics of Mn x Fe1-x Fe2O4 (x = 0-1) nanoparticles (NPs) in an AC magnetic field are evaluated by specific absorption rate (SAR) and intrinsic loss power, both of which are presented with varying NP composition, NP concentration, and field amplitudes. Mn0.75Fe0.25Fe2O4 exhibited superior induction heating properties in terms of a SAR of 153.76 W/g. This superior value of SAR with an optimized Mn2+ content is presented in correlation with the cation distribution of Mn2+ in the A or B position in the Fe3O4 structure and enhancement in magnetic saturation. These optimized Mn0.75Fe0.25Fe2O4 NPs can be used as a promising candidate for hyperthermia applications.

Novel epigenetic therapeutic strategies and targets in cancer.

The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical innovations in next generation sequencing. RNA interference, histone modification, DNA methylation and chromatin remodelling are epigenetic processes that control gene expression without causing mutations in the DNA. Although epigenetic abnormalities are thought to be a symptom of cell tumorigenesis and malignant events that impact tumor growth and drug resistance, physicians believe that related processes might be a key therapeutic target for cancer treatment and prevention due to the reversible nature of these processes. A plethora of novel strategies for addressing epigenetics in cancer therapy for immuno-oncological complications are currently available - ranging from basic treatment to epigenetic editing. - and they will be the subject of this comprehensive review. In this review, we cover most of the advancements made in the field of targeting epigenetics with special emphasis on microbiology, plasma science, biophysics, pharmacology, molecular biology, phytochemistry, and nanoscience.