Amitabha Acharya

Silica micro/nanospheres for theranostics: from bimodal MRI and fluorescent imaging probes to cancer therapy

Summary Nano-theranostics offer remarkable potential for future biomedical technology with simultaneous applications for diagnosis and therapy of disease sites. Through smart and careful chemical modifications of the nanoparticle surface, these can be converted to multifunctional tiny objects which in turn can be used as vehicle for delivering multimodal imaging agents and therapeutic material to specific target sites in vivo. In this sense, bimodal imaging probes that simultaneously enable magnetic resonance imaging and fluorescence imaging have gained tremendous attention because disease sites can be characterized quick and precisely through synergistic multimodal imaging. But such hybrid nanocomposite materials have limitations such as low chemical stability (magnetic component) and harsh cytotoxic effects (fluorescent component) and, hence, require a biocompatible protecting agent. Silica micro/nanospheres have shown promise as protecting agent due to the high stability and low toxicity. This review will cover a full description of MRI-active and fluorescent multifunctional silica micro/nanospheres including the design of the probe, different characterization methods and their application in imaging and treatment in cancer.

A bimodal molecular imaging probe based on chitosan encapsulated magneto-fluorescent nanocomposite offers biocompatibility, visualization of specific cancer cells in vitro and lung tissues in vivo

Multifunctional hybrid nanocomposite material, consists of chitosan encapsulated iron oxide (as MRI contrasting agent), CdS (as fluorescent probe) nanoparticles and podophyllotoxin (as anticancer drug) was synthesized and characterized. The TEM studies suggested the size of the NPs to be in the range of 80-100 nm. These nanocomposites were treated with different cancer cell lines viz., KB, C6 and A549 cells. Fluorescence imaging and Perls Prussian blue staining confirmed the presence of these nanocomposites inside both KB and C6 cells but not in A549 cells. Cytotoxicity experiments revealed that these biopolymer coated nanocomposites showed minimal toxicity towards cancerous cells. Further the intraperitoneal administration of one of the nanoformulations to Wistar rats suggested deposition of these nanocomposites in the lungs. The hematological, biochemical and histopathological analysis confirmed that these nanocomposites are safe to use as a novel dual mode imaging material.

A multifunctional magneto-fluorescent nanocomposite for visual recognition of targeted cancer cells

A multifunctional hybrid nanocomposite material of iron oxide nanoparticles and CdS quantum dots was synthesized by a direct amide coupling reaction. The prepared nanoparticles were characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and zeta potential studies. The TEM studies suggested that the sizes of the particles were in the range of 13.5 ± 1 nm. The energy dispersive x-ray (EDX) analysis confirmed the presence of Fe, Cd and S in the nanocomposites. To check the utility of this nanocomposite as a molecular imaging probe, these nanoparticles were further conjugated with folic acid. The folic acid conjugated nanocomposites were treated with rat glioma cells (C6, folic acid receptor over-expressing cell lines), human lung adenocarcinoma epithelial cells (A549, folic acid receptor negative cell lines) and normal mouse splenocytes for cell uptake and cytotoxicity studies. The nanoparticle internalization to C6 cells was confirmed by green fluorescence emission from these cells. Prussian blue staining studies suggested the intracellular presence of iron oxide. Further it was found that folic acid conjugated nanocomposites were significantly toxic to C6 cells only after 48 h but not to A549 cells or splenocytes. These studies indicated that the prepared nanocomposites have the potential to be used as delivery agent for magnetic and fluorescent materials towards folic acid receptor over-expressing cells and thus can find their application in the field of in vitro imaging diagnosis.

Fluorescent cadmium sulfide nanoparticles for selective and sensitive detection of toxic pesticides in aqueous medium

The detection of pesticide residues in ground water, food, or soil samples is extremely important. The currently available laboratory techniques have several drawbacks and needs to be replaced. Fluorescent chemosensors for pesticide detection were reported in the literature, with few reports published on quantum dot-based pesticide sensors, but none of these were focused toward differentiating organophosphorus and organochlorine pesticides specifically. In this respect, glutathione-coated CdS nanoparticles were synthesized and characterized. The TEM studies of the nanoparticles suggested mostly monodispersed spherical particles, with size in the range of 11.5±1 nm. The prepared fluorescent nanoparticles were found to selectively recognize organochlorine pesticide dicofol among all the other pesticides studied, by increasing the fluorescence intensity of the nanoparticles ~ 2.5 times. Similar studies carried out with organophosphorous pesticide dimethoate did not result any change in the fluorescence intensity of the nanoparticles. Further studies carried out with commercially available pesticide solutions, also confirmed similar results. The TEM, SEM, and DLS studies suggested aggregation of the nanoparticles in the presence of dicofol. Control experiments suggested possible role of both amine and carboxylic acid functional groups of glutathione in the recognition of dicofol. The limit of detection of dicofol was found to be ~ 55±11 ppb.Graphical AbstractGlutathione-coated CdS nanoparticles selectively recognize organochlorine pesticide dicofol among all the other pesticides studied, by increasing the fluorescence intensity of the nanoparticles. The TEM, SEM, and DLS studies suggested aggregation of the nanoparticles in the presence of dicofol.

Sustained delivery of BSA/HSA from biocompatible plant cellulose nanocrystals for in vitro cholesterol release from endothelial cells

Nanocomposites of plant cellulose nanocrystals (CNCs) were developed by binding model proteins BSA and HSA onto CNCs by physical adsorption and chemical conjugation methods The spectroscopy and microscopy studies confirmed the protein binding onto CNCs. Phosphate buffer saline (pH=4.0, 7.4) and simulated gastric and intestinal fluids (SGF/SIF; pH=1.1/6.5) showed maximum protein release of ∼62% over a period of time. The released proteins were found to retain both structural integrity as well as≥90% of bioactivity. Further, these cytocompatible nanocomposites showed ∼58-85% cholesterol release from HUVEC whereas no selectivity was observed for HCAEC. It is speculated that due to the presence of combination of shuttles (albumins) and sinks (CNCs and albumins), these prepared nanocomposites with increased cholesterol effluxing ability may serve as a potential candidate for future biomedical applications in pharmaceuticals.

Theragnosis: Nanoparticles as a Tool for Simultaneous Therapy and Diagnosis

Theragnostic NPs give new hope in simultaneous diagnosis and therapy of a disease at curable stage. Theragnosis is the fundamental requirement of personalized medicine. For successful theragnosis applications, the imaging agents and drugs should be efficiently delivered, resulting in adequate imaging signal or drug concentration in the targeted disease site. The selection of NPs for imaging, diagnosis and therapy was based on their biomimetic features with higher surface to volume ratio of the nanomaterials. The essential properties of nanomedicines involve early and precise diagnosis of clinical conditions providing an efficient treatment without secondary effects. Thus, nanotheragnostic probes are much better than conventional treatments where the diagnosis and therapy are way apart from each other. This chapter briefs about the recent advancement of nanotheragnosis research with future scope and associated hurdles.

Nanoscale Materials in Targeted Drug Delivery

Nanoscale materials (NSMs) are gaining attention due to their small size and unique physiochemical properties. Different approaches are used for the synthesis of NSMs. NSMs cannot be visualized by ordinary instruments. Instruments with high resolution are required for their characterisation. NSMs offer enhanced activity and specificity to encapsulate drugs. NSM are used as vehicles for site specific delivery of drugs inside the body. In this chapter, approaches for the synthesis of NSMs, and characterisation techniques for NSMs like SEM, TEM, AFM, DLS, XRD, and FTIR have been explained briefly. In addition, this chapter also covers zero dimensional one dimensional, two dimensional and three dimensional NSMs briefly. Detailed information about approaches of targeted delivery like passive and active have been covered in this chapter. NSMs like polymeric nanoparticles, metallic nanoparticles, liposomes, quantum dots, polymeric micelles, carbon nanotubes, dendrimers, and magnetic nanoparticles used in targeted drug delivery have also been explained in this chapter.

Cellular Response of Therapeutic Nanoparticles

Nanoparticles (NPs) are being extensively used in the field of nanomedicines. Different types of NPs are administered into the body by various routes. NPs come in contact with cells inside the body. Cellular response of NPs is affected by size, shape, surface chemistry, and cellular uptake pathways of NPs. In addition to this, type of cells, various cell lines, and growth media are also found to affect the cellular response of NPs. NPs induce diverse cellular responses like apoptosis, necrosis, and reactive oxygen species (ROS) production. NPs also form a protein corona inside the biological media which may alter their identity and behaviour as compared to bare NPs. In this chapter, we have made an attempt to throw light on cellular uptake pathways of NPs, monitoring of endocytic pathways followed by NPs, factors affecting cellular responses of therapeutic NPs, and protein corona formation, characterisation and its implications on fate of NPs.