5-FU mediated depletion of myeloid suppressor cells enhances T-cell infiltration and anti-tumor response in immunotherapy-resistant lung tumor.

Tumor microenvironment (TME) is a heterogeneous system consisting of both cellular and acellular components. The growth and progression of tumors rely greatly on the nature of TME, marking it as an important target in cancer immunotherapy. Lewis Lung Carcinoma (LLC) is an established murine lung cancer model representing immunologically 'cold' tumors characterized by very few infiltrated cytotoxic T-cells, high levels of Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs).

nCP:Fe Nanocontrast Agent for Magnetic Resonance Imaging-Based Early Detection of Liver Cirrhosis and Hepatocellular Carcinoma.

Early detection of liver tumors and cirrhotic lesions by magnetic resonance imaging (MRI) remains a great challenge. Here, we report a biomineral nanocontrast agent based on iron-doped nanocalcium phosphate (nCP:Fe-CA) for magnetic resonance imaging of early-stage liver cirrhotic and hepatocellular carcinoma nodules using rat models. We have optimized an intravenously injectable, aqueous suspension of nCP:Fe-CA having an average size of 137.

Exploiting the preferential phagocytic uptake of nanoparticle-antigen conjugates for the effective treatment of autoimmunity.

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, used as a model of multiple sclerosis.

nCP:Fe-A Biomineral Magnetic Nanocontrast Agent for Tracking Implanted Stem Cells in Brain Using MRI.

tracking of transplanted stem cells to monitor their migration, biodistribution, and engraftment in the host tissue is important for assessing the efficacy of stem cell therapeutics. Here, we report a biomineral nanocontrast agent, iron doped calcium phosphate nanoparticles (nCP:Fe), for the tracking of stem cells in brain using magnetic resonance imaging (MRI). We have synthesized ∼100 nm sized nCP nanoparticles doped with 9.

Magnetic 3D scaffold: A theranostic tool for tissue regeneration and non-invasive imaging in vivo.

We report an osteoconducting magnetic 3D scaffold using Fe doped nano-hydroxyapatite-Alginate-Gelatin (AGHFe1) for Magnetic Resonance Imaging based non-invasive monitoring of bone tissue regeneration. In rat cranial defect model, the scaffold facilitated non-invasive monitoring of cell migration, inflammatory response and matrix deposition by unique changes in transverse relaxation time (T2). Cell infiltration resulted in a considerable increase in T2 from ~37 to ~62 ms, which gradually returned to that of native bone (~23 ms) by 90 days.

Biomineral Nano-Theranostic agent for Magnetic Resonance Image Guided, Augmented Radiofrequency Ablation of Liver Tumor.

Theranostic nanoparticles based on biocompatible mineral compositions can significantly improve the translational potential of image guided cancer nano-therapy. Here, we report development of a single-phase calcium phosphate biomineral nanoparticle (nCP) with dual-mode magnetic resonance contrast (T1-T2) together with radiofrequency (RF) mediated thermal response suitable for image-guided RF ablation of cancer. The nanoparticles (NP) are engineered to provide dual MR contrast by an optimized doping concentration (4.

Theranostic 3-Dimensional nano brain-implant for prolonged and localized treatment of recurrent glioma.

Localized and controlled delivery of chemotherapeutics directly in brain-tumor for prolonged periods may radically improve the prognosis of recurrent glioblastoma. Here, we report a unique method of nanofiber by fiber controlled delivery of anti-cancer drug, Temozolomide, in orthotopic brain-tumor for one month using flexible polymeric nano-implant. A library of drug loaded (20 wt%) electrospun nanofiber of PLGA-PLA-PCL blends with distinct in vivo brain-release kinetics (hours to months) were numerically selected and a single nano-implant was formed by co-electrospinning of nano-fiber such that different set of fibres releases the drug for a specific periods from days to months by fiber-by-fiber switching.

Biodegradable Radiofrequency Responsive Nanoparticles for Augmented Thermal Ablation Combined with Triggered Drug Release in Liver Tumors.

Radiofrequency ablation (RFA) and doxorubicin (Dox) chemotherapy are separately approved for liver cancer therapy; however, both have limited success in the clinic due to suboptimal/nonuniform heating and systemic side effects, respectively. Here, we report a biodegradable nanoparticle (NP) system showing excellent RF hyperthermic response together with the ability to locally deliver Dox in the liver under RF trigger and control. The nanosystem was prepared by doping a clinically permissible dose (∼4.

Magnetic resonance functional nano-hydroxyapatite incorporated poly(caprolactone) composite scaffolds for in situ monitoring of bone tissue regeneration by MRI.

In this study, we have reported the incorporation of a multi-modal contrast agent based on hydroxyapatite nanocrystals, within a poly(caprolactone)(PCL) nanofibrous scaffold by electrospinning. The multifunctional hydroxyapatite nanoparticles (MF-nHAp) showed simultaneous contrast enhancement for three major molecular imaging techniques. In this article, the magnetic resonance (MR) contrast enhancement ability of the MF-nHAp was exploited for the purpose of potentially monitoring as well as for influencing tissue regeneration.

Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared in vivo imaging.

Combination of three imaging techniques such as nuclear, magnetic and near-infrared fluorescence can aid in improved diagnosis of disease by synergizing specific advantages of each of these techniques such as deep tissue penetration of radiation signals, anatomical and functional details provided by magnetic contrast and better spatial resolution of optical signals. In the present work, we report the development of a multimodal contrast agent based on calcium phosphate nanoparticles (nCP), doped with both indocyanine green (ICG) and Gadolinium (Gd(3+)), and labeled with 99m-Technetium-methylene diphosphonate ((99m)Tc-MDP) for combined optical, magnetic and nuclear imaging. In order to obtain the desired tri-modal contrast properties, the concentrations of ICG, Gd(3+) and (99m)Tc were optimized at ∼0.

Hemocompatibility and macrophage response of pristine and functionalized graphene.

Graphene and its derivatives are being proposed for several important biomedical applications including drug delivery, gene delivery, contrast imaging, and anticancer therapy. Most of these applications demand intravenous injection of graphene and hence evaluation of its hemocompatibility is an essential prerequisite. Herein, both pristine and functionalized graphene are extensively characterized for their interactions with murine macrophage RAW 264.

Highly biocompatible TiO₂:Gd³⁺ nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging.

We report the development of a novel magnetic nano-contrast agent (nano-CA) based on Gd(3+) doped amorphous TiO(2) of size ∼25 nm, exhibiting enhanced longitudinal relaxivity (r(1)) and magnetic resonance (MR) contrasting together with excellent biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T clinical MR imaging system revealed that the amorphous phase of doped titania has the highest r(1) relaxivity which is ∼2.

Development and haematotoxicological evaluation of doped hydroxyapatite based multimodal nanocontrast agent for near-infrared, magnetic resonance and X-ray contrast imaging.

Multimodal molecular imaging provides both anatomical and molecular information, aiding early stage detection and better treatment planning of diseased conditions. Here, we report development and nanotoxicity evaluation of a novel hydroxyapatite nanoparticle (nHAp) based multimodal contrast agent for combined near-infrared (NIR), MR and X-ray imaging. Under optimised wet-chemical conditions, we achieved simultaneous doping of nHAp (size ∼50 nm) with indocyanine green and Gd(3+) contributing to NIR contrast (∼750-850 nm), paramagnetic behaviour and X-ray absorption suitable for NIR, MR and X-ray contrast imaging, respectively.

A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent.

Multi-modal molecular imaging can significantly improve the potential of non-invasive medical diagnosis by combining basic anatomical descriptions with in-depth phenotypic characteristics of disease. Contrast agents with multifunctional properties that can sense and enhance the signature of specific molecular markers, together with high biocompatibility are essential for combinatorial molecular imaging approaches. Here, we report a multi-modal contrast agent based on hydroxyapatite nanocrystals (nHAp), which is engineered to show simultaneous contrast enhancement for three major molecular imaging techniques such as magnetic resonance imaging (MRI), X-ray imaging and near-infrared (NIR) fluorescence imaging.