Bionanotechnology: Next-Generation Therapeutic Tools

Biomaterial is a growing family of materials with specific physicochemical properties. Significant studies have been made to characterize the potential in vivo and in vitro toxicity of biomaterials. The cytotoxicity may be attributed to variations in the physicochemical properties, target cell types, particle dispersion methods, etc. The reported cytotoxicity effects mainly include the impact on the biological system and organ-specific toxicity such as CNS toxicity, lung toxicity, cardiac toxicity, dermal toxicity, gastrointestinal toxicity, etc. Despite cellular toxicity, the immunological effects of biomaterials, such as the activation of pulmonary macrophages and associated inflammation, have been extensively studied. In this chapter, the latest research results on the toxicological profiles of nanomaterials, highlighting both the cellular toxicities and the immunological effects, have been incorporated. This analysis also offers details on the overall status, patterns, and research needs for dealing with the toxicological behavior of biomaterials. 

 Because of their nano-size, biological compatibility, and ability to precisely engineer antigens displayed, payloads packaged, and destinations targeted, nanobiomaterials are gaining traction as next-generation therapeutic tools. Oncolytic viruses were the first to be exploited in cancer immunotherapy because these are natural cell killers and, in some cases, highly selective for cancerous cells. Further, oncolytic viruses can be engineered to encode immune-stimulators and therapeutic genes. However, for oncolytic viruses to work, it is essential to develop these as viable viruses with the ability to infect. This raises safety concerns and poses hurdles in regulatory approval. To circumvent this limitation, non-replicating viruses and virus-like particles have been explored for immunotherapeutic applications. The advantage of these is their inability to infect mammals, thereby eliminating bio-safety concerns. Nonetheless, concerns related to toxicity need to be addressed in each case. Several virus-like particle candidates are currently in preclinical development stages and show promise for clinical use via intertumoral administration, also referred to as vaccination in situ. In cases where in situ administration is not possible due to the absence of solid tumours or inaccessibility of the tumour, nano-biomaterials for systemic administration are desired, and extracellular vesicles fit this bill. Exosomes, in particular, can provide controlled abscopal effects – a property desirable for the treatment of metastatic cancer. This chapter discusses the state-of-the-art in the development of nano-biomaterials for immunotherapy. With a plethora of candidates in development and over two hundred clinical trials ongoing worldwide, nanobiomaterials hold great promise as effective cancer immunotherapies with minimal side effects.

Cancer consists of a wide range of diseases that are mainly driven by the continuous unregulated proliferation of cancer cells. Current treatment options include the use of chemotherapies, radiotherapy, and surgery. Recently, there was an increased interest in applying nanoparticles (NPs) in cancer diagnosis and treatment. NPs are materials in the size range 1 to 100 nm and can be classified based on their properties, shape, or size. They have attracted wide attention because of their versatile physicochemical properties, nanoscale sizes, high surface-to-volume ratios, favourable drug release profiles, and targeting modifications. Nanotechnology can be used to improve the personalisation of cancer diagnosis and treatment by enhancing the detection of cancer-specific biomarkers, imaging of tumours and their metastases, specific drug delivery to target cells, and real-time observation of treatment progression. This chapter will highlight the main types of lipid NPs with their preparation methods. The clinical applications of these lipid NPs in cancer diagnosis and treatment will be presented along with the currently approved drugs based on these NPs.

Despite global efforts for decades, the number of cancer cases is still on the rise. Although in recent times there has been significant improvement in immunotherapy, chemotherapy remains standard care for cancer patients alongside radiation and surgery. Chemotherapeutic drugs and diagnostic agents (MRI, PET, Ultrasound) lack specificity and often suffer from poor solubility and unwanted biodistribution. This results in unnecessary high dose requirements, systemic toxicity, and compromised quality of life for the patients. Beside therapy, early diagnosis is essential for the successful treatment and cure of cancer patients, just like any other disease. Therefore, a suitable delivery vehicle is always needed for the theranostic agents. Viral vectors are routinely used for the delivery of genetic material. But parallelly, nanoparticles made with biodegradable, non-toxic, and non-immunogenic polymers are often used as a carrier of chemotherapy drugs, diagnostic agents as well as genetic materials. Once decorated with specific ligands, these nanocontainers can deliver cargo molecules to target tissue and organs with high precision.

 Magnetic Nanoparticles (MNPs) have gained interest within the research community due to their therapeutic potential in a variety of medical applications. MNPs are generally composed of a metallic core stabilized by the addition of an outer shell that can be further functionalized through the absorbance or conjugation of various targeting ligands. The magnetic properties of these nanoparticles can be utilized for imaging, localized drug delivery, and enhanced diagnostic detection. This chapter highlights the applications of MNPs to enhance magnetic resonance imaging (MRI) capabilities and improve the delivery of therapeutic agents to difficult-to-reach areas in the body. In addition, recent advances in the use of MNPs in stem cell therapy for both the tracking and monitoring of stem cell distribution in the body and improving engraftment and differentiation in stem cell therapy are discussed. Finally, examples of the incorporation of MNPs in diagnostic assays to improve rapid and realtime detection capabilities of many diseases, including cancer, cardiovascular diseases, and pathogen infections, are provided. 

Theranostic nanomaterials hold the potential to revolutionize future disease management. Recent progress in nanomaterials technology and aptamer-base- -targeting molecules have promoted efficient theranostics models. Aptamers are unique three-dimensional structures consisting of oligonucleotide (25-80 nt) polymers. They are comparable to monoclonal antibodies in their receptor-driven binding efficacy toward specific target receptors and binding ability to specific target molecules with high affinity and specificity. Aptamers have several other advantages, including prolonged shelf life, little or no variation from batch to batch, and ease of chemical modifications for enhanced stability and targeting capacity. Owing to the advantages mentioned above, aptamers are attracting great attention in diverse applications ranging from therapy, drug delivery, diagnosis, and functional genomics as well as biosensing. Herein, the aim is to give an overview of aptamers, highlight the opportunities of their application as means of effective therapeutic tools as well as functionalize them as potential diagnostic probes. Furthermore, the diverse modifications of aptamers for theranostic purposes, including therapeutic agents and targeted delivery nanomaterials, are comprehensively summarized.

The recent accomplishment of the human genome and DNA discovery has led to the diagnosis of many diseases caused by imperfections in genes. These diseases involve gross disturbances in the number or arrangement of a person's chromosomes. Hence, gene therapy has become a promising new therapy for the treatment of somatic diseases, for example, malignant tumours [1], severe infectious diseases, such as AIDS [2], and many genetic disorders, including haemophilia and cystic fibrosis [3]. Gene therapy introduces a gene into human cells to replace, delete, or correct gene function to produce a therapeutic protein with the desired action. This adjustable gene can be used to cure any disease. In 1990, a gene therapy clinic was initiated to find treatment for severe combined immunodeficiency (SCID). However, the first success of gene therapy was not observed until 2000 when Cavazzana calvo et al. [4] reported a success using gene therapy for the treatment of SCID [4]. While it has been 30 years since the first gene therapy trial, gene therapy is still a high-risk treatment, and only a few drugs have been approved, such as Glybera® , Gendicine®, and Strimvelis® .

Nanomaterials have contributed to significant advancements in the realms of biotechnology and medicine. A holistic examination of the different biocompatible nanocomposites is discussed in this chapter. Their compatibility with state-of-the-art engineering techniques, such as additive manufacturing to design practical surgical implants, is also discussed. The importance and potential of nanocomposites and manufacturing processes in implantable medical device industries are also thoroughly considered. Nanomaterials' unique characteristics contrast with their large counterparts, such as high surfaces, reactivity, and reproducibility. Their incorporation in matrices has shown that the resultant composites' mechanical, chemical, and physical properties can be improved.Consequently, a wide variety of technical technologies, such as energy products, biomedical applications, micro-electrical equipment etc., have been intensively researched. Furthermore, the foundation for many new medicines and surgical instruments, including nanorobots, has been built on nanobiotechnology. It has been utilized in almost every medical sector, and its usage in the treatment of different diseases, such as cancer, neurobiology, cardiovascular disorders, joint and bone disorders, eye diseases, and infectious diseases, has been evident through different studies. Nanobiotechnology can promote diagnostics and the advancement of customized medicine, i.e., prescribing unique therapeutics that are tailored to an individual's needs. Many advances have already begun, and a definite effect on medicine practice will be felt in a decade.