Recent Progress in Pharmaceutical Nanobiotechnology: A Medical Perspective

Bio-inspired nanotechnology (biomimetic nanotechnology) is defined as the acquisition of nanomaterials or nanodevices and systems using the principles of biology during design or synthesis. Transferring a mechanism, an idea, or a formation from living systems to inanimate systems is an essential strategy. In this context, nanoparticles inspired by nature have many advantages, such as functionality, biocompatibility, low toxicity, diversity, and tolerability. It is known that biomimetic approaches have been used in materials science since ancient times. Today, it plays a crucial role in the development of drug delivery systems, imaging, and diagnostics in medical science. There is no doubt that interest and research in biomimetic approaches, which is an innovative approach and inspired by nature, will continue in the field of medicine and life sciences hereafter. Within the scope of this chapter, polymeric nanomedicines, monoclonal antibodies and related structures, cell and cell-membrane-derived biomimetic nanomedicines, bacteria-inspired nanomedicines, viral biomimetic nanomedicines, organelle-related nanomedicines, nanozymes, protein corona, and nanomedicine concepts and new developments will be elucidated.

Lipid nanocarriers have recently arisen with a wide range of uses and research areas, with the advantages they offer in virtue of their unique properties. They are easily synthesized, scaled up, biodegradable, proper to transport many bioactive components, have a high loading capacity, and are convenient for various routes of administration (parenteral, oral, dermal, ocular, etc.). These carriers overcome the problems of bioactive substances such as low solubility, plasma half-life and bioavailability, and side effects, as well as providing controlled release, local delivery, and targeting. Lipid-based nanoparticular systems can be categorized into two basic classes, vesicular and non-vesicular. While liposomes are the most widely used vesicular structures, solid lipid nanoparticles and nano-structured lipid carriers are non-vesicular nanocarriers. These nanocarriers have many medical uses, such as cancer therapy, gene therapy, photodynamic therapy, treatment of infectious diseases and neurodegenerative diseases, vaccines, imaging, etc. It is essential that the synthesis method of lipid-based nanocarriers and the components from which they are composed are selected in accordance with the medical application area and characterization studies are carried out. In this article, liposomes, solid lipid nanoparticles and nano-structured lipid carriers will be discussed as lipid-based nanocarriers, synthesis and characterization methods will be emphasized and examples from medical applications will be given.

The progress in nanoscience and advances in the fabrication, characterization, and modification of materials at the nanoscale have paved the way for the production and use of nanoparticles with different properties. Today, the chemical agents used in many therapies cannot achieve the desired effectiveness due to dose-dependent toxicity, low solubility and bioavailability, damage to non-target organs and tissues due to non-specificity, and side effects. Nanoparticle systems produced in different forms and compositions are one of the main approaches used to eliminate the negative aspects of conventional chemical agents. Among these nanoparticle systems, metallic nanoparticles represent a promising approach. During the last two decades, metallic nanoparticles (MNPs) have drawn great attention due to their optical, electrical, and physicochemical properties as well as their size-dependent properties. The large surface to volume ratio and surface reactivity of metallic nanoparticles provide great potential for combining them with different biological/chemical agents, as well as they can also be formulated as a bioactive nanoplatform alone. In this regard, the present chapter summarizes the general aspects of metallic nanoparticles, common methods for synthesis, and various applications in the biomedical field.

 The idea of using light as a therapeutic tool has been popular for thousands of years. Scientific discoveries in line with technological innovations have contributed to the advancement of photodynamic therapy as a therapeutic modality. Photodynamic therapy is based on the generation of highly reactive species that alter the molecular systematics of cells through interactions between light, photosensitizer, and molecular oxygen. It has a minimally invasive protocol that can be combined with other clinical methods or can be stand-alone. The development of photosensitizers with the integration of nanotechnological approaches has provided favorable results over the years in malignant and non-malignant diseases by facilitating target-site action, selectivity, and controllable drug release. This chapter presents a review of photodynamic therapy with its important aspects; history, mechanism of action, cellular effects, integration into nanoscale drug delivery systems, and combinational therapeutic approaches in cancer. 

Extracellular vesicles are molecules secreted by cells, wrapped in phospholipids and carrying some types of RNA, DNA and protein in their inner region. Extracellular vesicles are classified as apoptotic bodies, microvesicles, and exosomes based on their extent and formation process. Exosomes, which have the smallest structure, have received more attention than other extracellular vesicles. Exosomes contain different types of molecules in their structures. Cell membranes comprise a lipid bilayer and contain different cargo molecules and different surface receptors, depending on the cells of origin where biogenesis takes place. The biogenesis of exosomes begins within the endosomal system. Then they mature and are released out of the cell. The biogenesis of exosomes may be associated with the ESCRT complex and may depend on many molecules other than the ESCRT complex. Exosomes excreted by the origin cells are taken up by the target cells in different ways and show their effects. The effects of exosomes on their target cells may vary according to the cargo molecules they carry. They participate in cell-to-cell communication by sending different signals to distant or nearby target cells. Exosomes have a variety of pathological and physiological effects on disease and health. They have different effects on many diseases, especially cancer. They play an active role in cancer development, tumor microenvironment, angiogenesis, drug resistance and immune system. There are many diseases that can be used as a biomarker due to increased secretion from cells of origin in pathological conditions. In addition, exosomes can be utilized as drug transportation systems due to their natural structure. In addition, they are potential candidates as effective vaccines because of their effects on immune system cells or the effects of exosomes secreted from immune system cells.

Investigations to ascertain the physiological roles of carbohydrates in biological systems are being given more importance each day. Basically, carbohydrates are biomolecules with a wide range of biological functions, although they represent the primary energy source for metabolic processes. Carbohydrates are found as structural components in connective tissue in animal organisms. They also act as structural elements in both plant and bacterial cell walls. In the cell, they bind to lipids and proteins to form glycoconjugates called glycolipids, glycopeptides, glycoproteins and peptidoglycans. By binding to lipids and proteins on the cell surface, they perform as molecules that support intercellular adhesion and intercellular communication. Glycobiology is the science that investigates the structure, biosynthesis, and impacts of glycans on biological functions. In biology, glycoconjugates serve a variety of key roles. In mammalian cells, the majority of proteins are glycosylated, and this explains how proteins perform their various functions. In the future, these techniques will be crucial for the identification and treatment of specific diseases. The most major area of progress in glycobiology is the development of carbohydrate-based medicines.
Some diseases, including cancer, can be diagnosed via altered cell surface glycosylation pathways as a biomarker. Therefore, regulating glycosylation mechanisms and understanding the phenotypic characteristics of glycoconjugates are crucial steps in the design of novel strategies.
This chapter discusses the biosynthesis of glycoconjugates, their wide range of biological functions, and their significance for therapy

This review outlines major cancer targeting strategies for nanoparticle systems. Targeted therapies have superiority over conventional chemotherapy or radiotherapy methods. Nanoparticles as drug nanocarriers enable drug delivery to the tumoral regions. For targeted drug delivery, nanoparticles are designed and tailored depending on the cancer and the purpose of the targeting mechanism. In this review, nanoparticle targeting for cancer therapy was summarized into three sections: passive, active, and physical targeting. Each issue was described and discussed with recent nanoparticular studies and their findings. In addition, a combination of targeting with diagnostics and theranostics was also presented.

A tumor consists of not only cancer cells but also an ecosystem including different subpopulations. Cancer stem cells (CSCs) are a rare subpopulation in the tumor cell population. Traditional therapies, such as chemotherapy and radiotherapy target cancer cells except for CSCs. Therefore, the self-renewal and colony formation capacity of CSCs provides the recurrence of tumors as well as drug resistance. Different strategies are used to eradicate CSCs with the knowledge of CSC properties. The recent technologic revolution gives a chance to design nanoscale medicines for the effective treatment of CSCs. Nanoparticle-based delivery systems improve the transport of traditional therapeutic drugs across biological barriers with maximum bioavailability, less toxicity, and side effects, and take advantage in combination with specific CSC targets, controlled and site-specific release. This chapter summarizes the current models of CSCs, the molecular mechanisms leading to metastases and drug resistance of CSCs, strategies to target CSCs, examples of currently approved nanomedicine drugs and future perspectives.

Glioblastoma is one of the most aggressive and deadly types of cancer. The blood-brain barrier is the biggest obstacle to overcome in glioblastoma treatment. Nanomedicine, which describes the use of nanostructures in medicine, has significant potential for glioblastoma. Nanomedicine provides advantages in crossing the blood-brain barrier, increasing the amount and effectiveness of drugs reaching the cancer site, monitoring diagnosis and treatment through imaging agents, and increasing the effectiveness of treatments in combination applications. This chapter reviews current nanotechnology research in glioblastoma over the past few years. 

When NPs are included in a Biological environment, they associate with a large number of circulating proteins. As a result, they interact dynamically with each other. This structure, which is defined as PC, affects the physical parameters of NPs and causes positive or negative effects on them. PC composition is affected by many properties of NPs, such as size, shape, and surface charge. Therefore, various surface modifications on NPs directly affect PC formation and nature. Although many studies have been carried out to understand the formation and composition of the resulting PC structure, this area still maintains its popularity as a research topic. This review aims to briefly give an idea about the effect of proteins in metabolism on NPs designed as carrier molecules, the determination of these protein structures and the final fate of NPs after PC formation. 

Biosensors are analytical apparatus utilized for the qualitative and quantitative detection of various biological or non-biological analytes. Early diagnosis of diseases (cancer, infectious disease), monitoring environmental pollution, and ensuring food safety are very important in terms of individual and public health. Therefore, it is also crucial to detect these markers sensitively and accurately, with cheap and simple methods, especially despite limited resources. Nanoparticles, thanks to their nano size, provide wide areas of biosensing and amplify signals. In most of the works, it was observed that the limit of detection (LOD) value decreased and the selectivity improved in biosensors prepared using nanosystems compared to conventional sensors. In this respect, the results give us hope for the use of nanosystems in biosensors. In this section, the subject of biosensors is briefly mentioned and mainly studies on the use of nanoparticular/nanovesicular systems in the field of biosensors are included.

As our knowledge of developing technology and human biology increases, the need for changes in our perspectives on diseases and treatment modalities has emerged. The individual variation of diseases at the molecular level has long led to the abandonment of the one-fits-to-all approach. These changes at the molecular level are illuminated using -omics technologies and are among the most powerful tools in precision medicine. The discovery of new drug targets and biomarkers results in the structural elucidation of targets. Thus, it has been possible to develop new drug molecules as well as to select the appropriate drug for the target, the appropriate dose, and, when necessary, the appropriate drug combination. Awareness of the changes in diseases at the molecular level has also updated clinical research designs to make precision medicine applicable. In this section, information and examples of developments in precision medicine, diagnosis and treatment in precision medicine, as well as -omics technologies and other technologies are presented.

The safety and efficacy of each drug candidate, including nanomedicine considered for pharmaceutical use, primarily must be determined in vitro. In this context, the most widely used method is cytotoxicity tests, which include cell culture studies. It examines the parameters of membrane integrity, metabolite incorporation, structural alteration, survival and growth in tissue culture, enzyme assays, and the capacity for transplantation within the scope of viability tests. Within the scope of cell culture studies, tests related to apoptosis, which are effective in proper cell cycle, immune system and embryonic development, are also included. Another way to detect cell viability is to detect the biomolecules it expresses. Determination of protein expression is one of the preferred methods in this sense. Within the scope of this chapter, there is information about cell culture-based methods under these main subjects, which are applied to nanomedicines.

Imaging is developing very quickly in various study bases. Nowadays, due to the desire for the technology coming to imaging, it is widely used to detect molecular and structural targets in in vivo studies. The aim of developing new non-invasive imaging methods is to provide affordable, high-resolution images with minimal known side effects for studying the biological processes of living organisms. For this purpose, X-ray-based computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (UI), Nuclear imaging methods (positron emission tomography (PET), single-photon emission computed tomography (SPECT)), and optical imaging, are techniques widely used in imaging. Each of these has unique advantages and drawbacks. The background of imaging techniques and their developments have been shown in this chapter and we discuss in detail the use of optical imaging through bioluminescence, fluorescence, and Cerenkov luminescence techniques in various diseases for preclinical applications, early clinical diagnosis, treatment, and clinical studies.