The aim of this study was to evaluate the cytotoxicity and immune-stimulatory effect of Mesoporous silica nanoparticle (MSN) Nano-adjuvant on pro-inflammatory cytokines and pattern recognition receptors (PRR) genes expression in Caco-2/PBMC co-culture model. MSNs were synthesized and characterized by scanning electron microscope (SEM), Brunauer Emmett Teller (BET) and Barrett Joyner Halenda (BJH) techniques. The BET specific surface area of MSNs was around 947 m 2 /g and the total pore volume and average pore diameter were 1.5 cm 3 /g and 8.01 nm, respectively. At the concentration of 10 µg/mL, MSN showed a low and time-dependent cytotoxicity on Caco-2 cells, while no cytotoxic effect was observed for 0.1 and 1 µg/mL concentrations after 24, 48 and 72 h. The expression of pro-inflammatory cytokines genes (IL-1, IL-8 and TNF-α) in co-cultures treated with different concentrations of MSN showed a dose-dependent significant increase up to 17.44, 2.722 and 4.34 folds, respectively, while the expression augmentation of IL-1 gene was significantly higher than the others. This indicates slight stimulation of intestinal inflammation. Different concentrations of MSN significantly increased TLR4 and NOD2 expression to 4.14 and 2.14 folds, respectively. NOD1 was not affected significantly. It can be concluded that MSN might increase protective immune responses against antigens as a vaccine adjuvant candidate. It seems that stimulation of TNF-α, IL-1, and IL-8 expression in enterocytes probably transpires through the agonistic activity of MSN for TLRs including TLR4, while NOD2-associated signaling pathways are also involved. This study provides an overall picture of MSN as a novel and potent oral adjuvant for mucosal immunity.
Cancer nanotheranostics aims at providing alternative approaches to traditional cancer diagnostics and therapies. In this context, plasmonic nanostructures especially gold nanostructures are intensely explored due to their tunable shape, size and surface plasmon resonance (SPR), better photothermal therapy (PTT) and photodynamic therapy (PDT) ability, effective contrast enhancing ability in Magnetic Resonance imaging (MRI) and Computed Tomography (CT) scan. Despite rapid breakthroughs in gold nanostructures based theranostics of cancer, the translation of gold nanostructures from bench side to human applications is still questionable. The major obstacles that have been facing by nanotheranostics are specific targeting, poor resolution and photoinstability during PTT etc. In this regard, various encouraging studies have been carried out recently to overcome few of these obstacles. Use of gold nanocomposites also overcomes the limitations of gold nanostructure probes and emerged as good nanotheranostic probe. Hence, the present article discusses the advances in gold nanostructures based cancer theranostics and mainly emphasizes on the importance of gold nanocomposites which have been designed to decipher the past questions and limitations of in vivo gold nanotheranostics.
Green nanotechnology has drawn major attention because of its ecofriendly and economical biosynthetic protocols. Synthesis of gold nanoparticles (AuNPs) using plant secondary metabolites is considered as a safer and cheaper option. Plants contain phytochemicals that has been used traditionally for treatment of various diseases, and proved to be non-toxic to healthy tissues. These phytochemicals play an important role in bio-reduction processes as reducing and stabilizing agents, and renders NPs selective toxicity towards diseased tissues. The study reports on the synthesis of AuNPs using Acai berry (AB) and Elderberry (EB) extracts and their anti-cancer properties. Formation of berry-AuNPs was confirmed through measurement of physico-chemical properties. The stability of the AuNPs was tested in biocompatible solutions. Anti-cancer activity of berry extracts and AuNPs was evaluated on the prostate (PC-3) and pancreatic (Panc-1) cancer cells. The berry extracts did not show toxicity to the cells, except for AB extracts on PC-3 cells at higher concentrations. The berry-AuNPs showed potential anti-cancer activities, and these effects could be further exploited for treatment of both the prostate and pancreatic cancers. Further studies are required to study the NP mechanism of action and specificity, as well as identify the phytochemicals involved in the synthesis of AuNPs.
Globally, approximately 1 in 4 cancers in women are diagnosed as breast cancer (BC). Despite significant advances in the diagnosis and therapy BCs, many patients develop metastases or relapses. Hence, novel therapeutic strategies are required, that can selectively and efficiently kill malignant cells. Direct targeting of the genetic and epigenetic aberrations that occur in BC development is a promising strategy to overcome the limitations of current therapies, which target the tumour phenotype. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, composed of only an easily modifiable single guide RNA (sgRNA) sequence bound to a Cas9 nuclease, has revolutionised genome editing due to its simplicity and efficiency compared to earlier systems. CRISPR/Cas9 and its associated catalytically inactivated dCas9 variants facilitate the knockout of overexpressed genes, correction of mutations in inactivated genes, and reprogramming of the epigenetic landscape to impair BC growth. To achieve efficient genome editing in vivo , a vector is required to deliver the components to target cells. Gold nanomaterials, including gold nanoparticles and nanoclusters, display many advantageous characteristics that have facilitated their widespread use in theranostics, as delivery vehicles, and imaging and photothermal agents. This review highlights the therapeutic applications of CRISPR/Cas9 in treating BCs, and briefly describes gold nanomaterials and their potential in CRISPR/Cas9 delivery.
Globally, approximately 1 in 4 cancers in women are diagnosed as breast cancer (BC). Despite significant advances in the diagnosis and therapy BCs, many patients develop metastases or relapses. Hence, novel therapeutic strategies are required, that can selectively and efficiently kill malignant cells. Direct targeting of the genetic and epigenetic aberrations that occur in BC development is a promising strategy to overcome the limitations of current therapies, which target the tumour phenotype. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, composed of only an easily modifiable single guide RNA (sgRNA) sequence bound to a Cas9 nuclease, has revolutionised genome editing due to its simplicity and efficiency compared to earlier systems. CRISPR/Cas9 and its associated catalytically inactivated dCas9 variants facilitate the knockout of overexpressed genes, correction of mutations in inactivated genes, and reprogramming of the epigenetic landscape to impair BC growth. To achieve efficient genome editing in vivo, a vector is required to deliver the components to target cells. Gold nanomaterials, including gold nanoparticles and nanoclusters, display many advantageous characteristics that have facilitated their widespread use in theranostics, as delivery vehicles, and imaging and photothermal agents. This review highlights the therapeutic applications of CRISPR/Cas9 in treating BCs, and briefly describes gold nanomaterials and their potential in CRISPR/Cas9 delivery.
Excitotoxicity is a primary pathological process that occurs during stroke, traumatic brain injury (TBI), and global brain ischemia such as perinatal asphyxia. Excitotoxicity is triggered by an overabundance of excitatory neurotransmitters within the synapse, causing a detrimental cascade of excessive sodium and calcium influx, generation of reactive oxygen species, mitochondrial damage, and ultimately cell death. There are multiple potential points of intervention to combat excitotoxicity and downstream oxidative stress, yet there are currently no therapeutics clinically approved for this specific purpose. For a therapeutic to be effective against excitotoxicity, the therapeutic must accumulate at the disease site at the appropriate concentration at the right time. Nanotechnology can provide benefits for therapeutic delivery, including overcoming physiological obstacles such as the blood–brain barrier, protect cargo from degradation, and provide controlled release of a drug. This review evaluates the use of nano-based therapeutics to combat excitotoxicity in stroke, TBI, and hypoxia–ischemia with an emphasis on mitigating oxidative stress, and consideration of the path forward toward clinical translation.
In the last decade, the area of “omics research” has received tremendous recognition and found significances in the field of biomedicine. And so did develop the technologies for analyzing various kinds of biomolecules. The advances made in omics tools are quite diverse and advanced. In this chapter, we give an overview of two most common approaches used for the analysis of biomolecules, namely, electrospray ionization and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The conventional MALDI approach for biomolecular analysis relies on organic matrices for ionization of analytes, which have several disadvantages in analysis of small molecules. Here we discuss the types and application of nanomaterials in laser desorption/ionization mass spectrometry in the analysis of biomolecules. Additionally, examples of nanomaterial-assisted mass spectrometry imaging are discussed. Together this chapter provides insights into mass spectrometry and significance of nanomaterials in analysis of biomolecules, which have large-scale implications in the field of biomedicine.
Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide. The burden of TB is alarmingly high in developing countries, where diagnosis latent TB infection (LTBI), Extra-pulmonary tuberculosis (EPTB), drug-resistant tuberculosis (DR-TB), HIV-associated TB, and paediatric TB is still a challenge. This is mainly due to delayed or misdiagnosis of TB, which continues to fuel its worldwide epidemic. The ideal diagnostic test is still unavailable, and conventional methods remain a necessity for TB diagnosis, though with poor diagnostic ability. The nanoparticles have shown potential for the improvement of drug delivery, reducing treatment frequency and diagnosis of various diseases. The engineering of antigens/antibody nanocarriers represents an exciting front in the field of diagnostics, potentially flagging the way toward development of better diagnostics for TB. This chapter discusses the presently available tests for TB diagnostics and also highlights the recent advancement in the nanotechnology-based detection tests for M. tuberculosis.
Nanomedicine is emerging as a potential solution for many medical science problems and will drastically change the face of diagnostics, imaging, therapeutics, and drug delivery in the near future. The elevated use of inorganic and organic nanomaterials in medicinal science leads toward the development of potentially advanced and successful technologies. Nanomaterials are proven to be efficient drug carriers for the delivery of drug to the target site as well as for diagnostics of unnatural events in body. The conjugation of nanoparticles such as gold nanoparticles with antibiotics is found to accelerate the response of drugs severalfold. Similarly, in cancer imaging and therapy, the application of nanomaterials such as gold and iron oxide opens new dimensions of opportunities. There are certainly many challenges in front of researchers which need to be addressed such as compatibility, specificity, and toxicity of nanomaterials. The major pharmaceutical industries around the globe are presently more focused on the scientific research and developmental aspects of nanomedicine which is one of the major reasons of delayed or slow commercialization of nanomedicine in the market. It is believed that these under-research and under-trial drugs and technologies will soon get translated and be available in the market with the bright face of medicinal science.
Viral nanoparticles (VNPs) are versatile systems for the delivery of vaccines and other therapeutic agents for the treatment of diseases such as cancer or those related to the immune-system, degenerative diseases, and infections caused due to agents like viruses, bacteria, and fungi. Additionally, the VNPs are also used in molecular diagnostics, in the development of films and arrays for applications in electronics and tissue engineering, the design of data storage devices, and devices for tissue-specific imaging and therapy. The ability of viruses and bacteriophages to invade and infect different kinds of host cells empower them as suitable nanocarriers wherein they are able to cross biological barriers that obstruct drug delivery. VNPs are generally produced by genetic or chemical engineering by inserting heterologous sequences or ligands of interest into surface-exposed loops of the capsid protein (CPs). The CPs of viruses are the protein-building blocks that can self-assemble and are inherently biodegradable. The capsids that are generated artificially using the modified version of the CPs are known as virus-like particles (VLPs) to which ligands, peptides, and other agents are conjugated to generate VNPs. VNPs can self-assemble either as discrete structures or may organize themselves into films and arrays. Specific formulations of VNPs loaded with biomolecules such as antibodies and aptamers or biomimetics significantly improve efficacy and function by modulating tissue localization. The potential of VNP-based vaccine therapy is yet to be fully explored and it is expected that it will continue to evolve with more effective design and applicability for the treatment of various diseases.
AIDS is one of the most dreaded diseases of the twenty-first century caused by human immunodeficiency virus (HIV). Recently, there are reports which show decline in new infections due to better access to anti-retroviral drugs. Still on a daily basis, ~2356 new HIV infections are being reported globally. New treatments and anti-HIV drugs are being continuously developed with the aim to control and cure AIDS. The anti-HIV drugs that are in use usually target HIV entry and replication inside the host cells. However, these drugs are only partially effective in slowing the rate of HIV replication. Nevertheless, the virus manages to replicate at much slower rates even when anti-retroviral treatment is ongoing. The HIV seropositives who are on anti-retroviral treatment for long periods of time are now developing different kinds of other complications including neuroAIDS. The latest development in HIV therapy is a novel kind of bone marrow transplantation from donors who have a homozygous mutation in CCR5 gene.
Nanoparticles are three-dimensional particulates different from their parent compound and possess novel electrical, magnetic, and optical properties. They have applications in a variety of areas like medicine, engineering, environmental remediation, etc. Small particle size and high surface area further increase the exposure of NPs to humans through inhalation and dermal absorption. Use of NPs in our daily life is increasing everyday as a part of cosmetics, food, etc. Exposure of humans to NPs can cause modulation or alterations in cell signaling process. These NPs penetrate into the cell and disrupt normal functions. In recent years, there is a lack of information about the possible hazardous effect of nanoparticles on human health and disruption of endocrine system. NPs cause hormonal disruption, neurological and immune disorders, impact fertility, and act as endocrine disruptive chemicals (EDCs). EDCs disrupt the body’s normal function due to their ability to block or mimic a hormone’s natural function. EDCs include industrial (bisphenol A, PCB, plasticizers, dioxins, etc.) and synthetic chemicals (pesticides, solvents, etc.). Exposure of humans to EDCs is unavoidable, so there is a serious need to identify the compounds that have high impact on human health especially by acting through the hormonal system to alter cell signaling and functions. This review summarizes different types of NPs and their potential impact on hormone signaling and functioning of major systems in the human body.
The resurgence of bacteria that are resistant to most of all available antibiotics is a major challenge faced by scientists recently. Further research needs to be compelled to decipher other novel therapy to kill such multidrug-resistant bacteria. This nature of bacteriophage and the mechanisms of phage infection of bacteria are discussed herein. Also, we examined an existing body or research indicating the potential for a widespread application of phages as treatment therapy for many bacterial infections. Phages could be exploited as templates in efforts to fabricate nanomaterials for diverse application. Thus, mixed therapy of both phages and nanomaterials are in development and are used recently in vivo. Application of phage therapy-based nanoscience in breast cancer is discussed herein.
It is now well established that most of the tumors are heterogeneous in nature that comprise a population of cancer stem cells (CSCs) and differentiated cancer cells. Like normal stem cells, CSCs have also self-renewal, proliferation, and differentiation capacities that are responsible for the development of drug resistance and relapse. Therefore, targeting CSCs is essential for the elimination of tumor recurrence condition. Although several anti-CSC therapeutics have been used in clinics, they are found to have limited efficacy due to poor solubility, lesser stability, and short circulation time in the blood. Therefore, tools in nanomedicines are being used to tackle these limitations. Recently, nanodrug carriers have been used to target CSCs and somewhat eliminate drug resistance by targeting CSC metabolism, inhibiting drug transporters, disturbing CSC survival pathways, etc. Even with these progress, the challenges for targeting CSCs by nanomedicines still remain and open up plenty of space for further development and improvement in synthesizing drug carriers with higher efficacy. In this chapter, we summarize about CSCs and their biological characterization toward resistance, then discuss several anti-CSC therapeutic approaches based on nanomedicines in the current state of research and development, and finally overview their future directions.
The application of nanotechnology in cancer management is being studied for specifically targeting cancer cells and destroying them with minimum damage to healthy tissues or using the nanoscale devices to detect cancer cells before they have formed tumors. Since the nanoparticles are much smaller than human cells, they easily move in and out of most cells just like large biomolecules of our body and can easily interact with other molecules on the surface as well as inside of the cells. Though the technology is not more than four decades old, it has produced substantial number of nanodiagnostic and nanotherapeutic agents with higher efficiency and safety. Nanotechnology has given a new insight for cancer treatment because of its potential to overcome the side effects of chemotherapeutic agents. An array of nanovehicle platforms can be designed which can specifically target the cancerous tissues, have high drug-loading capacities, and are favorable for endocytic intracellular uptake.
