Current Topics in Medicinal Chemistry - Volume 20, Issue 30, 2020

Incorporating nanotechnology into fluorescent imaging and magnetic resonance imaging (MRI) has shown promising potential for accurate diagnosis of cancer at an earlier stage than the conventional imaging modalities. Molecular imaging (MI) aims to quantitatively characterize, visualize, and measure the biological processes or living cells at molecular and genetic levels. MI modalities have been exploited in different applications including noninvasive determination and visualization of diseased tissues, cell trafficking visualization, early detection, treatment response monitoring, and in vivo visualization of living cells. High-affinity molecular probe and imaging modality to detect the probe are the two main requirements of MI. Recent advances in nanotechnology and allied modalities have facilitated the use of nanoparticles (NPs) as MI probes. Within the extensive group of NPs, fluorescent NPs play a prominent role in optical molecular imaging. The fluorescent NPs used in molecular and cellular imaging can be categorized into three main groups including quantum dots (QDs), upconversion, and dyedoped NPs. Fluorescent NPs have great potential in targeted theranostics including cancer imaging, immunoassay- based cells, proteins and bacteria detections, imaging-guided surgery, and therapy. Fluorescent NPs have shown promising potentials for drug and gene delivery, detection of the chromosomal abnormalities, labeling of DNA, and visualizing DNA replication dynamics. Multifunctional NPs have been successfully used in a single theranostic modality integrating diagnosis and therapy. The unique characteristics of multifunctional NPs make them potential theranostic agents that can be utilized concurrently for diagnosis and therapy. This review provides the state of the art of the applications of nanotechnologies in early cancer diagnosis focusing on fluorescent NPs, their synthesis methods, and perspectives in clinical theranostics.

Central nervous system (CNS) cancers are among the most common and treatment-resistant diseases. The main reason for the low treatment efficiency of the disorders is the barriers against targeted delivery of anticancer agents to the site of interest, including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). BBB is a strong biological barrier separating circulating blood from brain extracellular fluid that selectively and actively prevents cytotoxic agents and majority of anticancer drugs from entering the brain. BBB and BBTB are the major impediments against targeted drug delivery into CNS tumors. Nanotechnology and its allied modalities offer interesting and effective delivery strategies to transport drugs across BBB to reach brain tissue. Integrating anticancer drugs into different nanocarriers improves the delivery performance of the resultant compounds across BBB. Surface engineering of nanovehicles using specific ligands, antibodies and proteins enhances the BBB crossing efficacy as well as selective and specific targeting to the target cancerous tissues in CNS tumors. Multifunctional nanoparticles (NPs) have brought revolutionary advances in targeted drug delivery to brain tumors. This study reviews the main anatomical, physiological and biological features of BBB and BBTB in drug delivery and the recent advances in targeting strategies in NPs-based drug delivery for CNS tumors. Moreover, we discuss advances in using specific ligands, antibodies, and surface proteins for designing and engineering of nanocarriers for targeted delivery of anticancer drugs to CNS tumors. Finally, the current clinical applications and the perspectives in the targeted delivery of therapeutic molecules and genes to CNS tumors are discussed.

Parkinson’s disease (PD) is one of the most prevalent and severe neurodegenerative disease affecting more than 6.1 million people globally. It is characterized by age-related progressive deterioration of neurological functions caused by neuronal damage or neuronal death. During PD, the dopamineproducing cells in the substantia nigra region of the brain degenerate, which leads to symptoms like resting tremors and rigidity. Treatment of PD is very challenging due to the blood-brain barrier, which restricts the drug from reaching the brain. Conventional drug delivery systems possess a limited capacity to cross the blood barrier, leading to low bioavailability and high toxicity (due to off-site drug release). Therefore, it becomes necessary to accelerate the development of novel drug delivery systems, including nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, and solid lipid nanoparticles for the treatment of PD. Exosomes are biological lipid bilayer membrane vesicles produced by nearly all mammalian cells. The characteristics of vesicles are unique to their cell of origin and are primarily involved in intracellular communication. Exosomes, due to their nanoscale size, could easily permeate across the central nervous system, which makes them ideal for targeting the neurons in the substantia nigra. Exosomes could be efficient drug carrier systems for brain targeting, which can increase the efficacy of the drug and minimize the side effects. The review aims at providing a broad updated view of exosomes and their application in the treatment of PD.

Traditional Chinese Medicine (TCM) is one of the ancient and most accepted alternative medicinal systems in the world for the treatment of health ailments. World Health Organization recognizes TCM as one of the primary healthcare practices followed across the globe. TCM utilizes a holistic approach for the diagnosis and treatment of cancers. The tumor microenvironment (TME) surrounds cancer cells and plays pivotal roles in tumor development, growth, progression, and therapy resistance. TME is a hypoxic and acidic environment that includes immune cells, pericytes, fibroblasts, endothelial cells, various cytokines, growth factors, and extracellular matrix components. Targeting TME using targeted drug delivery and nanoparticles is an attractive strategy for the treatment of solid tumors and recently has received significant research attention under precise medicine concept. TME plays a pivotal role in the overall survival and metastasis of a tumor by stimulating cell proliferation, preventing the tumor clearance by the immune cells, enhancing the oncogenic potential of the cancer cells, and promoting tumor invasion. Hepatocellular Carcinoma (HCC) is one of the major causes of cancer-associated deaths affecting millions of individuals worldwide each year. TCM herbs contain several bioactive phytoconstituents with a broad range of biological, physiological, and immunological effects on the system. Several TCM herbs and their monomers have shown inhibitory effects in HCC by controlling the TME. This study reviews the fundamentals and applications of targeting strategies for immunosuppressing TME to treat cancers. This study focuses on TME targeting strategies using TCM herbs and the molecular mechanisms of several TCM herbs and their monomers on controlling TME.

Nanotechnology and its allied modalities have brought revolution in tissue engineering and bone healing. The research on translating the findings of the basic and preclinical research into clinical practice is ongoing. Advances in the synthesis and design of nanomaterials along with advances in genomics and proteomics, and tissue engineering have opened a bright future for bone healing and orthopedic technology. Studies have shown promising outcomes in the design and fabrication of porous implant substrates that can be exploited as bone defect augmentation and drug-carrier devices. However, there are dozens of applications in orthopedic traumatology and bone healing for nanometer-sized entities, structures, surfaces, and devices with characteristic lengths ranging from tens 10s of nanometers to a few micrometers. Nanotechnology has made promising advances in the synthesis of scaffolds, delivery mechanisms, controlled modification of surface topography and composition, and biomicroelectromechanical systems. This study reviews the basic and translational sciences and clinical implications of the nanotechnology in tissue engineering and bone diseases. Recent advances in NPs assisted osteogenic agents, nanocomposites, and scaffolds for bone disorders are discussed.