Immune checkpoint inhibitors (ICIs) are revolutionizing the treatment of many cancers and have demonstrated their potential as 'cancer terminators'. However, ICI treatment also has constraints, such as its immune-related adverse events (irAEs) and therapeutic resistance. These drawbacks are gradually being overcome through better knowledge of the immune system, history of disease, duration of treatment, combinational drug regimes, adequate biomarkers, and effective patient response monitoring. In this review, we discuss the present ICI therapy landscape and its therapeutic outcomes for various diseases. We also highlight biomarkers related to the ICI response.
Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.
A tumor serves as a major avenue in drug development owing to its complexity. Conventional therapies against tumors possess limitations such as suboptimal therapeutic efficacy and extreme side effects. These display poor pharmacokinetics and lack specific targeting, with non-specific distribution resulting in systemic toxicity. Therefore, nanocarriers targeted against cancers are increasingly being explored. Nanomedicine aids in maintaining a balance between efficacy and toxicity by specifically accumulating in tumors. Nanotherapeutics possess advantages such as increased solubility of chemotherapeutics, encapsulation of multiple drugs and improved biodistribution, and can ensure tumor-directed drug delivery and release via the approaches of passive targeting and active targeting. This review aims to offer a general overview of the current advances in tumor-targeting nanocarriers for clinical and diagnostic use.
Gold nanoparticles (AuNPs) have garnered much attention as contrast agents for computerized tomography (CT) because of their facile synthesis and surface functionalization, in addition to their significant X-ray attenuation and minimal cytotoxicity. Cell labeling using AuNPs and tracking of the labeled cells using CT has become a time-efficient and cost-effective method. Actively targeted AuNPs can enhance CT contrast and sensitivity, and further reduce the radiation dosage needed during CT imaging. In this review, we summarize the state-of-the-art use of AuNPs in CT for cell tracking, including the precautionary steps necessary for their use and the difficulty in translating the process into clinical use.
Interest is increasing in the use of nanotheranostics as diagnosis, imaging and therapeutic tools for stroke management, but movement to the clinic remains challenging.
Peptides and proteins have emerged as potential therapeutic agents and, in the search for the best treatment regimen, the oral route has been extensively evaluated because of its non-invasive and safe nature. The physicochemical properties of peptides and proteins along with the hurdles in the gastrointestinal tract (GIT), such as degrading enzymes and permeation barriers, are challenges to their delivery. To address these challenges, several conventional and novel approaches, such as nanocarriers, site-specific and stimuli specific delivery, are being used. In this review, we discuss the challenges to the oral delivery of peptides and the approaches used to tackle these challenges.
Smart nanocarriers obtained from bacteria and viruses offer excellent biomimetic properties which has led to significant research into the creation of advanced biomimetic materials. Their versatile biomimicry has application as biosensors, biomedical scaffolds, immobilization, diagnostics, and targeted or personalized treatments. The inherent natural traits of biomimetic and bioinspired bacteria- and virus-derived nanovesicles show potential for their use in clinical vaccines and novel therapeutic drug delivery systems. The past few decades have seen significant progress in the bioengineering of bacteria and viruses to manipulate and enhance their therapeutic benefits. From a pharmaceutical perspective, biomimetics enable the safe integration of naturally occurring bacteria and virus particles to achieve high, stable rates of cellular transfection/infection and prolonged circulation times. In addition, biomimetic technologies can overcome safety concerns associated with live-attenuated and inactivated whole bacteria or viruses. In this review, we provide an update on the utilization of bacterial and viral particles as drug delivery systems, theranostic carriers, and vaccine/immunomodulation modalities.
The successful regulatory authority approval rate of drug candidates in the drug development pipeline is crucial for determining pharmaceutical research and development (R&D) efficiency. Regulatory authorities include the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceutical and Food Safety Bureau Japan (PFSB), among others. Optimal drug metabolism and pharmacokinetics (DMPK) properties influence the progression of a drug candidate from the preclinical to the clinical phase. In this review, we provide a comprehensive assessment of essential concepts, methods, improvements, and challenges in DMPK science and its significance in drug development. This information provides insights into the association of DMPK science with pharmaceutical R&D efficiency.
Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.
Aging is one of the major risk factors for most neurodegenerative disorders including Parkinson's disease (PD). More than 10 million people are affected with PD worldwide. One of the predominant factors accountable for progression of PD pathology could be enhanced accumulation of senescent cells in the brain with the progress of age. Recent investigations have highlighted that senescent cells can ignite PD pathology via increased oxidative stress and neuroinflammation. Senolytics are agents that kill senescent cells. This review mainly focuses on understanding the pathological connection between senescence and PD, with emphasis on some of the recent advances made in the area of senolytics and their evolution to potential clinical candidates for future pharmaceuticals against PD.
The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities.
Cryptides are a subfamily of bioactive peptides embedded latently in their parent proteins and have multiple biological functions. Cationic cryptides could be used as modern drugs in both infectious diseases and cancers because their mechanism of action is less likely to be affected by genetic mutations in the treated cells, therefore addressing a current unmet need in these two areas of medicine. In this review, we present the current understanding of cryptides, methods to mine them sustainably using available online databases and prediction tools, with a particular focus on their antimicrobial and anticancer potential, and their potential applicability in a clinical setting.