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CURATOR
A pinboard by
Sheikh Mohamed

Post Doctoral Researcher, Bio-Nano Electronics Research Centre

PINBOARD SUMMARY

Striving for the Evolution of Nano Revolution in Cancer Diagnostics and Treatment

Brain cancer is considered to be one of the most fatal subtype of cancer, primarily due to their position in the body and their highly aggressive nature. Natural physiological barriers such as blood-brain barrier (BBB) guard the brain in a tightly controlled manner, elevating the difficulty levels in treating brain related disorders, including brain tumors. While chemotherapeutics have limited access to tumors and high levels of non-specific toxicity (similar case as radiation therapy), surgery remains the only viable option for such a scenario. Still, the complications associated with surgery and high degree of tumor relapse pose as major hurdles. Nanoformulations are being considered as substantial alternatives to not only efficiently trespass the BBB but also for highly efficient and precision treatment modalities. Of the vastly researched nanoformulations, those composed of biodegradable and biocompatible materials are expected to show better bioavailability with reduced/nil toxicity. Many FDA approved cancer NFs are liposomal variants and are found to be efficient for broad cancer types. We have developed a similar kind of hybrid solid-lipid nanoformulation that has shown excellent safety profile when tested in nude mice. This hybrid nanoformulation exhibited extended blood circulation time, meaning it has more chances of accumulating in tumors translating in better treatment. The formulation, carrying a plant toxin as drug, was decorated with ligands specific for crossing the BBB/angiogenic blood vessels in the tumor and the tumor itself, making it a precisely targeted therapeutic formulation for brain tumor. The preliminary results were astounding with nearly 60% of mice cured of tumors without any relapse, a first of its kind outcome till now. The outstanding results have attracted attention from physicians, neurosurgeons, pharma and analytical companies, highlighting the significance of the study. We propose this formulation with suitable modifications for not only brain tumors, but also other brain neurodegenerative disorders as ischemia, Alzheimer’s, Parkinson’s etc and hard to treat hypoperfused tumors, fibrotic shield tumors etc.

16 ITEMS PINNED

Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer.

Abstract: Gliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks to in attaining fool proof treatment solutions. An initiative to curb such a scenario was successfully demonstrated in vitro, utilizing a multi-conceptual gold nanoparticle based photo-thermal and drug combination therapy.Gold nanoparticles (Au NPs) were synthesized with a highly environmentally benign process. The Au NPs were PEGylated and conjugated with folate and transferrin antibody to achieve a dual targeted nano-formulation directed towards gliomas. Curcin, a type 1 ribosome inactivating protein, was attached to the Au NPs as the drug candidate, and its multifarious toxic aspects analyzed in vitro. NIR photo-thermal properties of the Au nano-conjugates were studied to selectively ablate the glioma cancer colonies.Highly cyto-compatible, 10-15nm Au NP conjugates were synthesized with pronounced specificity towards gliomas. Curcin was successfully conjugated to the Au NPs with pH responsive drug release. Prominent toxic aspects of curcin, such as ROS generation, mitochondrial and cytoskeletal destabilization were witnessed. Excellent photo-thermal ablation properties of gold nanoparticles were utilized to completely disrupt the cancer colonies with significant precision.The multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass.With multifunctionality the essence of nanomedicine in recent years, the present nanoconjugate highlights itself as a viable option for a multimodal treatment option for brain cancers and the like.

Pub.: 24 Dec '13, Pinned: 25 Sep '17

Theranostic Liposome-Nanoparticle Hybrids for Drug Delivery and Bioimaging.

Abstract: Advanced theranostic nanomedicine is a multifunctional approach which combines the diagnosis and effective therapy of diseased tissues. Here, we investigated the preparation, characterization and in vitro evaluation of theranostic liposomes. As is known, liposome-quantum dot (L-QD) hybrid vesicles are promising nanoconstructs for cell imaging and liposomal-topotecan (L-TPT) enhances the efficiency of TPT by providing protection against systemic clearance and allowing extended time for it to accumulate in tumors. In the present study, hydrophobic CdSe/ZnS QD and TPT were located in the bilayer membrane and inner core of liposomes, respectively. Dynamic light scattering (DLS), zeta potential (ζ) measurements and fluorescence/absorption spectroscopy were performed to determine the vesicle size, charge and spectroscopic properties of the liposomes. Moreover, drug release was studied under neutral and acidic pH conditions. Fluorescence microscopy and flow cytometry analysis were used to examine the cellular uptake and intracellular distribution of the TPT-loaded L-QD formulation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to investigate the in vitro cytotoxicity of the formulations on HeLa cells. According to the results, the TPT-loaded L-QD hybrid has adequate physicochemical properties and is a promising multifunctional delivery vehicle which is capable of a simultaneous co-delivery of therapeutic and diagnostic agents.

Pub.: 04 Jul '17, Pinned: 25 Sep '17

Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner.

Abstract: Angiogenesis is essential for the development of malignant tumors and provides important targets for tumor diagnosis and therapy. To noninvasively assess the angiogenic profile of tumors, novel alpha(v)beta(3) integrin-targeted ultrasmall superparamagnetic iron oxide particles (USPIOs) were designed and their specific uptake by endothelial cells was evaluated in vitro and in vivo. USPIOs were coated with 3-aminopropyltrimethoxysilane (APTMS) and conjugated with Arg-Gly-Asp (RGD) peptides. Accumulation in human umbilical vein endothelial cells (HUVECs) was evaluated using Prussian blue staining, transmission electron microscopy, magnetic resonance (MR) imaging, and inductively coupled plasma mass spectrometry. Uptake of RGD-USPIO by HUVECs was significantly increased when compared with unlabeled USPIO and could be competitively inhibited by addition of unbound RGD. The ability of the RGD-USPIO to noninvasively distinguish tumors with high (HaCaT-ras-A-5RT3) and lower (A431) area fractions of alpha(v)beta(3) integrin-positive vessels was evaluated using a 1.5-T MR scanner. Indeed, after RGD-USPIO injection, there was a more pronounced decrease in T(2) relaxation times in HaCaT-ras-A-5RT3 tumors than in A431 tumors. Furthermore, T(2)*-weighted images clearly identified the heterogeneous arrangement of vessels with alpha(v)beta(3) integrins in HaCaT-ras-A-5RT3 tumors by an irregular signal intensity decrease. In contrast, in A431 tumors with predominantly small and uniformly distributed vessels, the signal intensity decreased more homogeneously. In summary, RGD-coupled, APTMS-coated USPIOs efficiently label alpha(v)beta(3) integrins expressed on endothelial cells. Furthermore, these molecular MR imaging probes are capable of distinguishing tumors differing in the degree of alpha(v)beta(3) integrin expression and in their angiogenesis profile even when using a clinical 1.5-T MR scanner.

Pub.: 20 Feb '07, Pinned: 25 Sep '17

Glioblastoma multiforme: a review of therapeutic targets.

Abstract: Glioblastoma is the commonest primary brain tumor, as well as the deadliest. Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: survival after diagnosis is about 1 year. Established prognostic factors are limited, but include age, Karnofsky performance status, mini-mental status examination score, O6-methylguanine methyltransferase promoter methylation and extent of surgery. Standard treatment includes resection of > 95% of the tumor, followed by concurrent chemotherapy and radiotherapy. Nevertheless, GBM research is being conducted worldwide at a remarkable pace, in the laboratory and at the bedside, with some of the more recent promising studies focused on identification of aberrant genetic events and signaling pathways to develop molecular-based targeted therapies, tumor stem cell identification and characterization, modulation of tumor immunological responses and understanding of the rare long-term survivors. With this universally fatal disease, any small breakthrough will have a significant impact on survival and provide hope to the thousands of patients who receive this diagnosis annually. This review describes the epidemiology, clinical presentation, pathology and tumor immunology, with a focus on understanding the molecular biology that underlies the current targeted therapeutics being tested.

Pub.: 05 May '09, Pinned: 25 Sep '17