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Exosomes are small nanosized biovesicles that form when multivesicular bodies and the plasma membrane fuse and are released into the surrounding body fluids. They are best known for their multifunction in mediating intercellular communication by transferring various biomolecules, including DNA, RNAs, proteins, and lipids, in a short- and long-distance manner and have been identified as health and disease messengers. Importantly, exosomes are necessary for various physiological processes in health and disease. The generation of exosomes depends on the status of the disease, which usually exhibits opposite roles by inducing enhanced cellular stress and damage. Recently, exosome-based nanotechnologies have provided unprecedented opportunities to boost the developments of exosome-related biology, chemistry, pathology, and therapeutics in different diseases based on their unique structural/compositional/morphological characteristics for next-generation nanomedicines. Herein, we provide a comprehensive overview of the recent advances in exosome nanotechnology research, including their classification, isolation and preparation, constitution, biological function, and nanobiomedical applications in disease treatment and diagnosis. Furthermore, future prospects were also concluded. This review will provide more inspiration for promoting the development of exosome-based advanced theranostic nanoplatforms and nanotechnology.

INTRODUCTION Lymphatic filariasis (LF), also known as elephantiasis, has been recognized by the world health organization and the centers for disease control and prevention as one of the neglected tropical diseases. The huge prevalence and risk of manifestation to date reflect the poor management of this disease. The disease poses vast public health and socio-economic burdens and generates a dire need for the development of a prophylactic solution for mass administration. AREAS COVERED Vaccination has been a sought-out strategy for dealing with ever-evolving infectious diseases and can be duly tuned to become a cost effective means of disease control and eventual eradication. In this review, we highlight the epidemiology of LF with the current diagnosis and treatment modules. The need for the development of a potential vaccine candidates, and challenges are discussed. The evidence presented in this review aims to enlighten the readers regarding the essential factors governing LF and its management using prophylactic measures. EXPERT OPINION The complex nature of filarial parasites is evident from the absence of a single vaccine for LF. The development and selection of an appropriate preclinical model and its translation into clinical practice is deemed to be a major task needing in-depth evaluation to formulate an effective vaccine. Explorations of the existing vaccine platforms would serve to be an apt strategy in this direction.

The expansion in the knowledge and applications of probiotics is on a constant rise over decades. The history of vaccine development, on the other hand, ranges back to the early nineteenth century and has been advancing ever since. Design of probiotic-based vaccine has been a boon and can be an important contributor in the field of immunization. Building up the human immunological tolerance has been the aim in order to achieve a superior level of human longevity. Orally deliverable vaccines have been preferred over the conventional parenteral formulations owing to their high patient compliance and ease of delivery. Bacteria and yeast are among the most prevalent microbiota utilized as probiotics, and owing to their significant immunomodulatory effects, they have garnered attention as promising candidates for developing edible vaccine. A legion of organisms has been regarded as safe for human consumption, thereby encouraging their adoption into probiotic-based vaccine development. A variety of bacteria- and yeast-based edible probiotic vaccines are highlighted in this chapter catering to a plethora of physiological conditions in humans. The chapter is majorly devoted to representation of the most frequently applied strategies involving bacteria and yeast in the conception of oral probiotic vaccines, both preclinically and clinically. Despite the presence of conglomerate vaccine-based strategies, a quest for newer probiotic oral vaccine platforms still persists.

Tolerance induction is central to the suppression of autoimmunity. Here, we engineered the preferential uptake of nano-conjugated autoantigens by spleen-resident macrophages to re-introduce self-tolerance and suppress autoimmunity. The brain autoantigen, myelin oligodendrocyte glycoprotein (MOG), was conjugated to 200 or 500 nm silica nanoparticles (SNP) and delivered to the spleen and liver-resident macrophages of experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis. MOG-SNP conjugates significantly reduced signs of EAE at a very low dose (50 μg) compared to the higher dose (>800 μg) of free-MOG. This was associated with reduced proliferation of splenocytes and pro-inflammatory cytokines secretion, decreased spinal cord inflammation, demyelination and axonal damage. Notably, biodegradable porous SNP showed an enhanced disease suppression assisted by elevated levels of regulatory T cells and programmed-death ligands (PD-L1/2) in splenic and lymph node cells. Our results demonstrate that targeting nano-conjugated autoantigens to tissue-resident macrophages in lymphoid organs can effectively suppress autoimmunity.

The intranasal pathway, with its inherent virtues of circumvention of blood-brain barrier, evasion of hepatic/first-pass metabolism, noninvasiveness, and ease of administration, has attracted a great deal of attention in the field of drug delivery to the brain. With the advent of nanotechnology, few of the limitations associated with intranasal delivery like mucociliary clearance, nasal irritation, and limited absorption across the nasal epithelium could be overcome by careful design of nanocarriers that can be even targeted to specific regions of the brain. A host of therapeutic agents including drugs, peptides, nucleic acids, and nanocarriers encapsulating various cargo have been investigated for administration via intranasal pathway, and a few of them have been already approved in clinical use. Treatment of innumerous brain-related diseases/disorders like cancer, migraine, cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, and several other neurodegenerative disorders has been attempted using this mode of administration. However, this alternate pathway has been sparsely explored for diagnostic or theranostic applications involving the brain. In this chapter, we discuss about the intranasal pathway from a diagnostic and theranostic aspect and present examples of brain-related diseases that would benefit from intranasal imaging and theranostic approaches.

Glioblastoma multiforme (GBM) is the most common and aggressive form of the primary brain tumors in humans. The intricate pathophysiology, the development of resistance by tumor cells, and the inability of the drugs to effectively cross the blood-brain and blood-tumor barriers result in poor prognosis for GBM patients, with a median survival time of only 1 to 2 years. Nose-to-brain delivery offers an attractive, noninvasive strategy to enhance drug penetration or transport novel drug/gene carriers into the brain. Although the exact mechanism of intranasal delivery remains elusive, the olfactory and trigeminal nerve pathways have been found to play a vital role in circumventing the traditional barriers of brain targeting. This review discusses the intranasal pathway as a novel domain for delivering drugs and nanocarriers encapsulating drugs/genes, as well as stem cell carriers specifically to the glioma cells. Considering the fact that most of these studies are still in preclinical stage, translating such intranasal delivery strategies from bench to bedside would be a critical step for better management and prognosis of GBM. Graphical abstract.

In the recent past, there has been a marked increase in the research utilizing nature as a “bio-laboratory” for eco-friendly synthesis of nanoparticles with controlled morphologies and unique properties. Several biotemplates sourced from plants, microorganisms, marine ecosystem, etc., have been explored for the biosynthesis of metallic and metal oxide nanoparticles. These bionanoparticles have been utilized for a diverse range of applications including catalysis, solar energy, water treatment, nanotherapeutics, drug delivery, diagnostics, etc. This chapter deals with the use of marine resources for the development of bionanoparticles for anticancer applications. The marine ecosystem provides abundant bioactives that may have a significant impact in the development of pharmaceutical and nanotechnology products. Marine algae and microorganisms have been widely studied for their natural ability to sequester metal ions and synthesize inorganic nanoparticles either intracellularly or extracellularly. Marine polysaccharides represent a new class of biomaterials that is still underutilized and have the potential to act as reducing as well as stabilizing agents influencing the surface properties of the biosynthesized nanoparticles. They also have been explored for surface modification of prepared nanoparticles for conferring biocompatibility and surface functionality. The exact mechanism of biosynthesis of nanoparticles using different marine resources is yet to be elucidated. In addition, although these green nanoparticles have been reported to have inherent biocompatibility and selective toxicity to cancer cells, a mechanistic approach to unravel their exact mode of action, comprehensive toxicity studies, and clinical trials are warranted before they can be put to clinical use.

The discovery of new therapeutic agents and targets depending upon the pathophysiology of various diseases has necessitated the delivery of therapeutic molecules to specific cellular sub-compartments. The efficiency of various treatments can be improved by carefully designing new therapeutic strategies involving modifications of nanocarriers enabling organelle-specific targeting of bioactives. In order to do that, in-depth studies to unravel the pathophysiology of diseases, internalization and intracellular trafficking pathways, as well as the time-dependent fate and release of encapsulated cargo from nanocarriers within the organelles are much needed. Despite the interdisciplinary efforts from the fields of medicine, materials science, and engineering, and the development of various nanomedicines with a precise control over their physical and chemical attributes, the subcellular targeted delivery still presents formidable challenges. Further, considering the fact that drug repurposing is now gaining interest, an intersection of nanocarriers and drug repurposing would provide key benefits like reduced time, cost, and risk in developing safer and more effective treatments for several indications. The significant opportunities and challenges in further progress toward bench-to-bedside translation of organelle-targeted nanomedicines are discussed in this chapter.

Layer-by-layer (LbL) technique was employed to modify the surface of doxorubicin (Dox)-loaded bovine serum albumin (BSA) nanoparticles using hyaluronic acid (HA) to enable targeted delivery to overexpressed CD44 receptors in metastatic breast cancer cells. LbL technique offers a versatile approach to modify the surface of colloidal nanoparticles without any covalent modification. Dox-loaded BSA (Dox Ab) nanoparticles optimized for their size, zeta potential, and drug encapsulation efficiency were prepared by modified desolvation technique. The cellular uptake and cytotoxicity of the LbL coated Dox Ab nanoparticles were analyzed in CD44 overexpressing breast cancer cell line MDA-MB-231. Nanoparticles with HA as the final layer (Dox Ab HA) showed maximum cellular uptake in MDA-MB-231 cells owing to the CD44 receptor-mediated endocytosis and hence, exhibited more cytotoxicity as compared to free Dox. Further, luciferase-transfected MDA-MB-231 cells were used to induce tumor in BALB/c female nude mice to enable whole body tumor imaging. The mice were imaged before and after Dox treatment to visualize the tumor growth. The in vivo biodistribution of Dox Ab HA nanoparticles in nude mice showed maximum accumulation in tumor, and importantly, better tumor reduction in comparison with free Dox, thus paving the way for improved drug delivery into tumors.

Enzyme-and pH-responsive polyelectrolyte nanocapsules having diameters in the range of 200 +/- 20 nm were fabricated by means of Layer-by-Layer assembly of biopolymers, protamine, and heparin, and then loaded with anticancer drug doxorubicin. The incorporation of the FDA-approved peptide drug protamine as a wall component rendered the capsules responsive to enzyme stimuli. The stimuli-responsive drug release from these nanocapsules was evaluated, and further modulation of capsule permeability to avoid premature release was demonstrated by crosslinking the wall components. The interaction of the nanocapsules with cancer cells was studied using MCF-7 breast cancer cells. These capsules were readily internalized and disintegrated inside the cells, culminating in the release of the loaded doxorubicin and subsequent cell death as observed by confocal microscopy and MTT Assay. The bioavailability studies performed using BALB/c mice revealed that the encapsulated doxorubicin exhibited enhanced bioavailability compared to free doxorubicin. Our results indicate that this stimuli-responsive system fabricated from clinically used FDA-approved molecules and exhibiting minimal premature release has great potential for drug-delivery applications.