Suraj Dixit - Academia.edu (original) (raw)

Papers by Suraj Dixit

Nanomedicine (London, England), Jan 22, 2016

Glioblastoma multiforme is a devastating disease with no curative options due to the difficulty i... more Glioblastoma multiforme is a devastating disease with no curative options due to the difficulty in achieving sufficient quantities of effective chemotherapies into the tumor past the blood-brain barrier. Micelles loaded with temozolomide (TMZ) were designed to increase the delivery of this drug into the brain. pH-responsive micelles composed of distearoyl phosphoethanolamine-PEG-2000-amine and N-palmitoyl homocysteine were surface-functionalized with PDGF peptide and Dylight 680 fluorophore. PDGF-micelles containing TMZ have specific uptake and increased killing in glial cells compared with untargeted micelles. In vivo studies demonstrated selective accumulation of PDGF-micelles containing TMZ in orthotopic gliomas implanted in mice. Targeted micelle-based drug carrier systems hold potential for delivery of a wide variety of hydrophobic drugs thereby reducing its systemic toxicity.

Current neuropharmacology, Jan 23, 2016

Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elemen... more Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as are delivery techniques that address the difficulty in crossing the blood brain barrier (BBB). Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanop...

American Journal of Transplantation

Molecular Pharmaceutics, 2015

Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed... more Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed to address intratumoral heterogeneity of glioblastomas that overexpress multiple cell surface receptors to ultimately improve therapeutic efficacy. AuNPs conjugated with peptides against both the epidermal growth factor and transferrin receptors and loaded with the photosensitizer phthalocyanine 4 (Pc 4) have been designed and compared with monotargeted AuNPs for in vitro and in vivo studies. The (EGFpep+Tfpep)-AuNPs-Pc 4 with a particle size of ∼41 nm improved both specificity and worked synergistically to decrease time of maximal accumulation in human glioma cells that overexpressed two cell surface receptors as compared to cells that overexpressed only one. Enhanced cellular association and increased cytotoxicity were achieved. In vivo studies show notable accumulation of these agents in the brain tumor regions.

Nanoscale, 2015

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also ... more Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

RSC Advances, 2013

We encapsulated gadolinium oxide (Gd 2 O 3 ) nanoparticles within phospholipid micelles as a nove... more We encapsulated gadolinium oxide (Gd 2 O 3 ) nanoparticles within phospholipid micelles as a novel low cytotoxic T 1 -weighted MRI imaging contrast agent (MGdNPs) that can also deliver small molecules such as DNA plasmids. MGdNPs show relatively good MRI relaxivity values, negligible cytotoxicity, excellent cellular uptake and expression of DNA plasmids in vivo. Biodistribution studies in mice show that intranasal and intraperitoneal administration of MGdNPs can effectively target specific organs.

Journal of Electroanalytical Chemistry, 2012

Graphene has remarkable electrochemical properties that make it an ideal material for constructin... more Graphene has remarkable electrochemical properties that make it an ideal material for constructing biosensors,however it has not been explored for DNA biosensing. Herein, we report on a chitosan-modified graphene platform for the electrochemical detection of changes in DNA sequences. For this purpose, graphene synthesized chemically and characterized by Raman spectroscopy and Transmission electron microscopy, was covalently modified with positively charged chitosan to facilitate the immobilization of a single-stranded DNA `capture' oligonucleotide. The covalent attachment of chitosan to graphene was confirmed by FT-IR spectroscopy and then the capture DNA was immobilized on to the chitosan modified graphene electrode. Then, the target DNA (complementary or mismatched `mutant' DNA) was applied to the electrode and cyclic voltammetry was performed. The results of the voltammetric experiments indicate that the chitosan modified graphene electrodes immobilized with ssDNA+complementary DNA exhibit a significantly higher magnitude of redox peak current than the chitosan modified graphene electrodes immobilized with the non-complementary mutant DNAs. Together, these results demonstrate that the chitosan-graphene platform provides a rapid, stable and sensitive detection of mismatched DNA and has the potential to be used for point-of-care diagnostic tests for specific DNA mutations associated with disease conditions.

Chemistry of Materials, 2006

The development of hybrid polymer particles formed by the hydrolytic condensation of octadecyldim... more The development of hybrid polymer particles formed by the hydrolytic condensation of octadecyldimethyl(3-trimethoxysilylpropyl)ammonium chloride (ODMACl) and the trisodium salt of the triacetic acid N-(trimethoxysilylpropyl)ethylenediamine (TANED) along with self-assembling with nonionic poly-(ethylene glycol) (PEG) based surfactants containing a hydrophobic octadecyl tail (Brij) have been studied using liquid and solid-state NMR, dynamic light scattering (DLS), transmission electron microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and small-angle X-ray scattering (SAXS). On the basis of DLS and NMR data, the mechanism of interaction of Brij, ODMACl, and TANED molecules in an aqueous solution has been suggested. The influence of the PEG chain length on the ability of surfactants to stabilize polymer particles has been established. The combination of DSC and XRD assessed the crystallinity and thermal properties of self-assembled hybrid materials in the solid state, while SAXS studies revealed that their morphology strikingly depends on the PEG chain length and reaction conditions determining the degree of Brij incorporation and the structure of the Brij-ODMACl complex. Because of the protective PEG shell, the hybrid polymer particles were successfully used as soluble templates for the formation of iron oxide nanoparticles.

RSC Adv., 2015

In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses ... more In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses of endothelial cell (EC) inflammation when subjected to oxidative stress, such as observed in organ transplantation. Targeted Rapamycin Micelles (TRaM) were synthesized using PEG-PE-amine and N-palmitoyl homocysteine (PHC) with further tailoring of the micelle using targeting peptides (cRGD) and labeling with far-red fluorescent dye for tracking during cellular uptake studies. Our results revealed that the TRaM was approximately 10 nm in diameter and underwent successful internalization in Human Umbilical Vein EC (HUVEC) lines. Uptake efficiency of TRaM nanoparticles was improved with the addition of a targeting moiety. In addition, our TRaM therapy was able to downregulate both mouse cardiac endothelial cell (MCEC) and HUVEC production and release of the pro-inflammatory cytokines, IL-6 and IL-8 in normal oxygen tension and hypoxic conditions. We were also able to demonstrate a dose-dependent uptake of TRaM therapy into biologic tissues ex vivo. Taken together, these data demonstrate the feasibility of targeted drug delivery in transplantation, which has the potential for conferring local immunosuppressive effects without systemic consequences while also dampening endothelial cell injury responses.

Nanomedicine (London, England), Jan 22, 2016

Glioblastoma multiforme is a devastating disease with no curative options due to the difficulty i... more Glioblastoma multiforme is a devastating disease with no curative options due to the difficulty in achieving sufficient quantities of effective chemotherapies into the tumor past the blood-brain barrier. Micelles loaded with temozolomide (TMZ) were designed to increase the delivery of this drug into the brain. pH-responsive micelles composed of distearoyl phosphoethanolamine-PEG-2000-amine and N-palmitoyl homocysteine were surface-functionalized with PDGF peptide and Dylight 680 fluorophore. PDGF-micelles containing TMZ have specific uptake and increased killing in glial cells compared with untargeted micelles. In vivo studies demonstrated selective accumulation of PDGF-micelles containing TMZ in orthotopic gliomas implanted in mice. Targeted micelle-based drug carrier systems hold potential for delivery of a wide variety of hydrophobic drugs thereby reducing its systemic toxicity.

Current neuropharmacology, Jan 23, 2016

Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elemen... more Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as are delivery techniques that address the difficulty in crossing the blood brain barrier (BBB). Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanop...

American Journal of Transplantation

Molecular Pharmaceutics, 2015

Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed... more Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed to address intratumoral heterogeneity of glioblastomas that overexpress multiple cell surface receptors to ultimately improve therapeutic efficacy. AuNPs conjugated with peptides against both the epidermal growth factor and transferrin receptors and loaded with the photosensitizer phthalocyanine 4 (Pc 4) have been designed and compared with monotargeted AuNPs for in vitro and in vivo studies. The (EGFpep+Tfpep)-AuNPs-Pc 4 with a particle size of ∼41 nm improved both specificity and worked synergistically to decrease time of maximal accumulation in human glioma cells that overexpressed two cell surface receptors as compared to cells that overexpressed only one. Enhanced cellular association and increased cytotoxicity were achieved. In vivo studies show notable accumulation of these agents in the brain tumor regions.

Nanoscale, 2015

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also ... more Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

RSC Advances, 2013

We encapsulated gadolinium oxide (Gd 2 O 3 ) nanoparticles within phospholipid micelles as a nove... more We encapsulated gadolinium oxide (Gd 2 O 3 ) nanoparticles within phospholipid micelles as a novel low cytotoxic T 1 -weighted MRI imaging contrast agent (MGdNPs) that can also deliver small molecules such as DNA plasmids. MGdNPs show relatively good MRI relaxivity values, negligible cytotoxicity, excellent cellular uptake and expression of DNA plasmids in vivo. Biodistribution studies in mice show that intranasal and intraperitoneal administration of MGdNPs can effectively target specific organs.

Journal of Electroanalytical Chemistry, 2012

Graphene has remarkable electrochemical properties that make it an ideal material for constructin... more Graphene has remarkable electrochemical properties that make it an ideal material for constructing biosensors,however it has not been explored for DNA biosensing. Herein, we report on a chitosan-modified graphene platform for the electrochemical detection of changes in DNA sequences. For this purpose, graphene synthesized chemically and characterized by Raman spectroscopy and Transmission electron microscopy, was covalently modified with positively charged chitosan to facilitate the immobilization of a single-stranded DNA `capture' oligonucleotide. The covalent attachment of chitosan to graphene was confirmed by FT-IR spectroscopy and then the capture DNA was immobilized on to the chitosan modified graphene electrode. Then, the target DNA (complementary or mismatched `mutant' DNA) was applied to the electrode and cyclic voltammetry was performed. The results of the voltammetric experiments indicate that the chitosan modified graphene electrodes immobilized with ssDNA+complementary DNA exhibit a significantly higher magnitude of redox peak current than the chitosan modified graphene electrodes immobilized with the non-complementary mutant DNAs. Together, these results demonstrate that the chitosan-graphene platform provides a rapid, stable and sensitive detection of mismatched DNA and has the potential to be used for point-of-care diagnostic tests for specific DNA mutations associated with disease conditions.

Chemistry of Materials, 2006

The development of hybrid polymer particles formed by the hydrolytic condensation of octadecyldim... more The development of hybrid polymer particles formed by the hydrolytic condensation of octadecyldimethyl(3-trimethoxysilylpropyl)ammonium chloride (ODMACl) and the trisodium salt of the triacetic acid N-(trimethoxysilylpropyl)ethylenediamine (TANED) along with self-assembling with nonionic poly-(ethylene glycol) (PEG) based surfactants containing a hydrophobic octadecyl tail (Brij) have been studied using liquid and solid-state NMR, dynamic light scattering (DLS), transmission electron microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and small-angle X-ray scattering (SAXS). On the basis of DLS and NMR data, the mechanism of interaction of Brij, ODMACl, and TANED molecules in an aqueous solution has been suggested. The influence of the PEG chain length on the ability of surfactants to stabilize polymer particles has been established. The combination of DSC and XRD assessed the crystallinity and thermal properties of self-assembled hybrid materials in the solid state, while SAXS studies revealed that their morphology strikingly depends on the PEG chain length and reaction conditions determining the degree of Brij incorporation and the structure of the Brij-ODMACl complex. Because of the protective PEG shell, the hybrid polymer particles were successfully used as soluble templates for the formation of iron oxide nanoparticles.

RSC Adv., 2015

In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses ... more In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses of endothelial cell (EC) inflammation when subjected to oxidative stress, such as observed in organ transplantation. Targeted Rapamycin Micelles (TRaM) were synthesized using PEG-PE-amine and N-palmitoyl homocysteine (PHC) with further tailoring of the micelle using targeting peptides (cRGD) and labeling with far-red fluorescent dye for tracking during cellular uptake studies. Our results revealed that the TRaM was approximately 10 nm in diameter and underwent successful internalization in Human Umbilical Vein EC (HUVEC) lines. Uptake efficiency of TRaM nanoparticles was improved with the addition of a targeting moiety. In addition, our TRaM therapy was able to downregulate both mouse cardiac endothelial cell (MCEC) and HUVEC production and release of the pro-inflammatory cytokines, IL-6 and IL-8 in normal oxygen tension and hypoxic conditions. We were also able to demonstrate a dose-dependent uptake of TRaM therapy into biologic tissues ex vivo. Taken together, these data demonstrate the feasibility of targeted drug delivery in transplantation, which has the potential for conferring local immunosuppressive effects without systemic consequences while also dampening endothelial cell injury responses.