Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis.

Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM-1 s-1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.

Nanotheranostic Probe Built on Methylene Blue Loaded Cucurbituril [8] and Gold Nanorod: Targeted Phototherapy in Combination with SERS Imaging on Breast Cancer Cells.

Recent advancements in a nanoarchitecture platform for safe and effective targeted phototherapy in a synergistic fashion is an absolute necessity in localized cancer therapy. Photothermal and photodynamic therapies (PTT and PDT) are considered as the most promising localized therapeutic intervention for cancer management as they have no long-term side effects and are minimally invasive and affordable. Herein, we have demonstrated a tailor-made nanotheranostic probe in which macrocyclic host cucurbituril [8] (CB[8]) is placed as a glue between two gold nanorods (GNRs) within ∼3 nm gaps in linear nanoassemblies with exquisitely sensitive plasmonics that exert combined phototherapy to investigate the therapeutic progression on human breast cancer cells. Photosensitizer methylene blue was positioned on CB[8] to impart the PDT effect, whereas GNR was responsible for PTT on a single laser trigger ensuring the synchronized phototherapy. Furthermore, the nanoconstruct was tagged with targeting anti-Her2 monoclonal antibody (MB-CB[8]@GNR-anti-Her2) for localized PTT and PDT on Her2 positive SKBR3 cells, subsequent cellular recognition by surface-enhanced Raman spectroscopy (SERS) platform, and further assessment of the combined intracellular phototherapy. Hence, the current strategy is definitely marked as a proof-of-concept straightforward approach that implies the perfect nature of the combined phototherapy to achieve an efficient cancer treatment.

Asialoglycoprotein receptor targeted optical and magnetic resonance imaging and therapy of liver fibrosis using pullulan stabilized multi-functional iron oxide nanoprobe.

Early diagnosis and therapy of liver fibrosis is of utmost importance, especially considering the increased incidence of alcoholic and non-alcoholic liver syndromes. In this work, a systematic study is reported to develop a dual function and biocompatible nanoprobe for liver specific diagnostic and therapeutic applications. A polysaccharide polymer, pullulan stabilized iron oxide nanoparticle (P-SPIONs) enabled high liver specificity via asialogycoprotein receptor mediation. Longitudinal and transverse magnetic relaxation rates of 2.15 and 146.91 mM-1 s-1 respectively and a size of 12 nm, confirmed the T2 weighted magnetic resonance imaging (MRI) efficacy of P-SPIONs. A current of 400A on 5 mg/ml of P-SPIONs raised the temperature above 50 °C, to facilitate effective hyperthermia. Finally, a NIR dye conjugation facilitated targeted dual imaging in liver fibrosis models, in vivo, with favourable histopathological results and recommends its use in early stage diagnosis using MRI and optical imaging, and subsequent therapy using hyperthermia.

Nanohybrids of Magnetically Intercalated Optical Metamaterials for Magnetic Resonance/Raman Imaging and In Situ Chemodynamic/Photothermal Therapy.

Target-specific reactive oxygen species (ROS)-based cancer treatments with high therapeutic efficacy and minimal side effects have been identified recently as a potentially effective cancer management strategy. Herein, we report the fabrication of a targeted nanotheranostic agent built on an iron oxide nanoparticle-decorated graphene-gold hybrid [plasmonic magnetic nanoprobe (PMNP)] for self-guided magnetic resonance (MR)/surface-enhanced Raman scattering imaging and photothermal therapy (PTT)/chemodynamic therapy (CDT). In the presence of glutathione, which is abundant in the tumor environment, the iron oxide nanoparticles undergo in situ reduction, which in turn generates hydroxyl radicals via a Fenton reaction to realize targeted destruction of tumor cells. Moreover, the localized production of heat benefited from the near-infrared absorption of the PMNP accelerates the intratumoral ROS generation process, with a synergistic effect of CDT/PTT. Furthermore, the probe offers an accurate visualization of the intracellular localization of the material through SERS/MR dual imaging channels. In view of the advantages offered by the tumor-specific stimuli-responsive nature of the probe, the PMNP presents as an effective tool for cancer management.

Semi-Supervised Nonnegative Matrix Factorization of Wide-Field Fluorescence Microscopic Images for Tissue Diagnosis.

This study tests the use of a constrained nonnegative matrix factorization (NMF) algorithm to explore the comparatively new field of chemometric microscopy to support tissue diagnosis. The algorithm can extract the spectral signature and the absolute concentration map of endogenous fluorophores from wide-field microscopic images. The resultant data distinguished normal and fibrous calvarial tissues, based on the changes in their spectral signatures. The absolute concentration map of endogenous fluorophores, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), and lipofuscin were derived from microscopic images and compared with the fluorescence from pure fluorophores. While the absolute concentration of NADH increased, the same of FAD and lipofuscin decreased from a normal to fibrous calvarial condition. An increase in the optical redox ratio, possibly due to the metabolic changes during the development of fibrosis, was observed. Differentiating tissue types using the absolute concentration map was found to be considerably more precise than that achievable with relative concentration. The quantification of fluorophores with reference to the absolute concentration map can eliminate uncertainties due to system responses or measurement details, thereby generating more biologically apposite data. Wide-field microscopy augmented with a constrained NMF algorithm could emerge as an advanced diagnostic tool, potentially heralding the emergence of chemometric microscopy.

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach.

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR-PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR-PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.

Real Time Imaging and Dynamics of Hippocampal Zn2+ under Epileptic Condition Using a Ratiometric Fluorescent Probe.

Zinc, the essential trace element in human body exists either in the bound or free state, for both structural and functional roles. Insights on Zn2+ distribution and its dynamics are essential in view of the fact that Zn2+ dyshomeostasis is a risk factor for epileptic seizures, Alzheimer's disease, depression, etc. Herein, a bipyridine bridged bispyrrole (BP) probe is used for ratiometric imaging and quantification of Zn2+ in hippocampal slices. The green fluorescence emission of BP shifts towards red in the presence of Zn2+. The probe is used to detect and quantify the exogenous and endogenous Zn2+ in glioma cells and hippocampal slices. The dynamics of chelatable zinc ions during epileptic condition is studied in the hippocampal neurons, in vitro wherein the translocation of Zn2+ from presynaptic to postsynaptic neuronal bodies is imaged and ratiometrically quantified. Raman mapping technique is used to confirm the dynamics of Zn2+ under epileptic condition. Finally, the Zn2+ distribution was imaged in vivo in epileptic rats and the total Zn2+ in rat brain was quantified. The results favour the use of BP as an excellent Zn2+ imaging probe in biological system to understand the zinc associated diseases and their management.

Gold nanorods decorated with a cancer drug for multimodal imaging and therapy.

Cancer, a condition with uncontrolled cell division, is the second leading cause of death worldwide. The currently available techniques for the imaging and treatment of cancer have their own limitations and hence a combination of more than one modality is expected to increase the efficacy of both diagnosis and treatment. In the present study, we have developed a multimodal imaging and therapeutic system by incorporating a chemotherapeutic drug, mitoxantrone (MTX) onto PEG coated gold nanorods (GNR). Strong absorption in the near-infrared (NIR) and visible regions qualifies GNR as an efficient photothermal (PTT) agent upon irradiation with either a NIR or visible laser. Additionally, the enhanced electric field of GNR makes it a suitable substrate for surface enhanced Raman scattering (SERS). Modification of GNR with amino PEG offers biocompatibility without affecting its optical property. In order to achieve tumor specificity, GNR-PEG was conjugated with tumor specific marker that can target cancer cells, leaving the normal cells unaffected. The incorporation of fluorescent chemotherapeutic drug mitoxantrone onto GNR-PEG facilitates chemotherapy as well as fluorescence imaging. The therapeutic efficacy of the developed GNR based system is tracked using fluorescence imaging and Raman imaging. The careful design of the system also facilitates the controlled release of the drug by photothermal triggering. Likewise, the imaging modality could be chosen as either Raman or fluorescence to monitor drug release in accordance with irradiation. The physico-chemical properties, and drug release profiles under different physiological conditions have been well studied. Finally, the developed system was tested for its therapeutic efficacy using cancer cells, in vitro. The receptor mediated cell uptake was more effective in folate receptor over-expressing cancer cells than in the normal and low-expressing cells. Accordingly the percentage of cell death was higher in folate receptor over-expressing cancer cells, which was further enhanced due to the effect of the dual therapeutic approach. The cell uptake and treatment efficacy was monitored using fluorescence microscopy and SERS. In conclusion, the developed GNR-PEG-MTX system is found to be an efficient multimodal therapeutic agent against cancer which could be tracked using two different techniques.