Computed tomography-guided additive manufacturing of Personalized Absorbable Gastrointestinal Stents for intestinal fistulae and perforations
2020; 228: 119542
Multi-"Color" Delineation of Bone Microdamages Using Ligand-Directed Sub-5 nm Hafnia Nanodots and Photon Counting CT Imaging
ADVANCED FUNCTIONAL MATERIALS
Biodegradable Biliverdin Nanoparticles for Efficient Photoacoustic Imaging
2019; 13 (7): 7690–7704
Small bowel perforations and obstructions are relatively frequent surgical emergencies, are potentially life-threatening, and have multiple etiologies. In general, treatment requires urgent surgical repair or resection and at times can lead to further complications. Stents may be used to help with healing intestinal perforations but use is limited as currently available stents are non-absorbable, are manufactured in a narrow size range, and/or are limited to usage in locations that are accessible for endoscopic removal post-healing. The use of 3D-printed bioresorbable polymeric stents will provide patients with a stent that can prevent leakage, is tailored specifically to their geometry, and will be usable within the small bowel, which is not amenable to endoscopic stent placement. This work focused on the rapid manufacturing of gastrointestinal stents composed of a polycaprolactone-polydioxanone (PCL-PDO) composite. Dynamic Mechanical Analysis (DMA) tests were conducted to separately analyze the effects of composition, the filament formation process, and physiological temperature on the PCL-PDO material properties. The proposed stent design was then modeled using computer-aided design, and Finite Element Analysis (FEA) was used to simulate the effects of physiologically relevant forces on stent integrity. The presence of hydrolysable ester bonds was confirmed using FT-IR spectroscopy. In vitro studies were used to evaluate the biocompatibility of the polymer composite. Further analyses were conducted through stent placement in ex vivo pig intestines. PCL-PDO stents were then 3D-printed and placed in vivo in a pig model.
View details for DOI 10.1016/j.biomaterials.2019.119542
View details for Web of Science ID 000498320900003
View details for PubMedID 31678842
Pro-Nifuroxazide Self-Assembly Leads to Triggerable Nanomedicine for Anti-cancer Therapy
ACS APPLIED MATERIALS & INTERFACES
2019; 11 (20): 18074–89
Photoacoustic imaging has emerged as a promising imaging platform with a high tissue penetration depth. However, biodegradable nanoparticles, especially those for photoacoustic imaging, are rare and limited to a few polymeric agents. The development of such nanoparticles holds great promise for clinically translatable diagnostic imaging with high biocompatibility. Metabolically digestible and inherently photoacoustic imaging probes can be developed from nanoprecipitation of biliverdin, a naturally occurring heme-based pigment. The synthesis of nanoparticles composed of a biliverdin network, cross-linked with a bifunctional amine linker, is achieved where spectral tuning relies on the choice of reaction media. Nanoparticles synthesized in water or water containing sodium chloride exhibit higher absorbance and lower fluorescence compared to nanoparticles synthesized in 2-(N-morpholino)ethanesulfonic acid buffer. All nanoparticles display high absorbance at 365 and 680 nm. Excitation at near-infrared wavelengths leads to a strong photoacoustic signal, while excitation with ultraviolet wavelengths results in fluorescence emission. In vivo photoacoustic imaging experiments in mice demonstrated that the nanoparticles accumulate in lymph nodes, highlighting their potential utility as photoacoustic agents for sentinel lymph node detection. The biotransformation of these agents was studied using mass spectroscopy, and they were found to be completely biodegraded in the presence of biliverdin reductase, a ubiquitous enzyme found in the body. Degradation of these particles was also confirmed in vivo. Thus, the nanoparticles developed here are a promising platform for biocompatible biological imaging due to their inherent photoacoustic and fluorescent properties as well as their complete metabolic digestion.
View details for DOI 10.1021/acsnano.9b01201
View details for Web of Science ID 000477786400033
View details for PubMedID 31246412
Design, Synthesis, and Characterization of Globular Orphan Nuclear Receptor Regulator with Biological Activity in Soft Tissue Sarcoma
JOURNAL OF MEDICINAL CHEMISTRY
2018; 61 (23): 10739–52
Transcription factor STAT3 has been shown to regulate genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of great biological significance. However, many small-molecule agents with potential effects through STAT3 modulation in cancer therapy lack aqueous solubility and high off-target toxicity, hence impeding efficient bioavailability and activity. This work, for the first time, reports a prodrug-based strategy for selective and safer delivery of STAT3 inhibitors designed toward metastatic and drug-resistant breast cancer. We have synthesized a novel lipase-labile SN-2 phospholipid prodrug from a clinically investigated STAT3 inhibitor, nifuroxazide (Pro-nifuroxazide), which can be regioselectively cleaved by the membrane-abundant enzymes in cancer cells. Pro-nifuroxazide self-assembled to sub 20 nm nanoparticles (NPs), and the cytotoxic ability was screened in ER(+)-MCF-7 and ER(-)-MD-MB231 cells at 48-72 h using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide proliferation assay. Results indicated that Pro-nifuroxazide NPs are multifold more effective toward inhibiting cancer cells in a time-dependent manner compared to parent nifuroxazide. A remarkable improvement in the local concentration of drugs to as high as ∼240 fold when assembled into NPs is presumably the reason for this functional improvement. We also introduced molecular dynamics simulations to generate Pro-nifuroxazide nano-assembly, as a model assembly from triggerable anti-cancer drugs, to provide molecular insights correlating physicochemical and anti-cancer properties. In silico properties of Pro-nifuroxazide including size, chemistry of NPs and membrane interactions with individual molecules could be validated by in vitro functional activities in cells of breast cancer origin. The in vivo anti-cancer efficiencies of Pro-nifuroxazide NPs in nude mice xenografts with MCF-7 revealed remarkable growth inhibition of as high as 400%. Histopathological analysis corroborated these findings to show significantly high nuclear fragmentation and retracted cytoplasm. Immunostaining on tumor section demonstrated a significantly lower level of pSTAT-3 by Pro-nifuroxazide NP treatment, establishing the inhibition of STAT-3 phosphorylation. Our strategy for the first time proposes a translatable prodrug agent self-assembled into NPs and demonstrates remarkable enhancement in IC50, induced apoptosis, and reduced cancer cell population through STAT-3 inhibition via reduced phosphorylation.
View details for DOI 10.1021/acsami.9b01343
View details for Web of Science ID 000469288300003
View details for PubMedID 31013055
Biodegradable nano carbon- based smart filters for efficient remediation of pharmaceutical contaminants
JOURNAL OF MATERIALS CHEMISTRY A
2018; 6 (45): 22951–57
Synthesis of Chiral Carbo-Nanotweezers for Enantiospecific Recognition and DNA Duplex Winding in Cancer Cells
ACS APPLIED MATERIALS & INTERFACES
2018; 10 (44): 37886–97
Sarcomas are rare and heterogeneous cancer variants of mesenchymal origin. Their genetic heterogeneity coupled with uncertain histogenesis makes them difficult to treat and results in poor prognosis. In this work, we show that structure-based drug discovery involving computational modeling can be used to identify a new retinoid X receptor (RXR) agonist ligand with a bis(indolyl)methane scaffold. This agent co-self-assembles with an amphiphilic diblock copolymer resulting in nanoparticles (Nano-RXR) with excellent kinetic stability, which were evaluated for efficacy and safety in transformed sarcoma cells, 63-3 Cre and 141-10 Cre of pig origin, and in rodent xenograft models. Responses at gene and protein levels established the treatment approach as a highly effective RXR agonist across cell, rodent, and "Oncopig" models. Interestingly, Nano-RXR was not only able to modulate metabolic and transporter genes related to orphan nuclear receptors but also played a major role in modulating programmed cell death in sarcomas developed in Oncopigs.
View details for DOI 10.1021/acs.jmedchem.8b01387
View details for Web of Science ID 000453488200026
View details for PubMedID 30375864
Chirality Inversion on the Carbon Dot Surface via Covalent Surface Conjugation of Cyclic alpha-Amino Acid Capping Agents
2018; 29 (11): 3913–22
Targeting the DNA of tumor cells with small molecules may offer effective clinical strategies for transcriptional inhibition. We unveil synthesis and characterization of ∼20 nm chiral carbon nanoparticles for enantiospecific recognition of DNA. Our approach inculcates chirality in carbon nanoparticles by controlled tethering of minor groove binders, i.e., Tröger's base (TB). The chiral particles positively enriched the cellular nucleus in MCF-7 breast cancer cells, irrespective of the TB asymmetry tethered on the particle surface, but negatively induced chiral carbon nanoparticles exhibited improved efficiency at inhibiting cell growth. Further studies indicated that these chiral particles act as nanotweezers to perturb the genomic DNA and induce apoptosis cascade in cancer cells.
View details for DOI 10.1021/acsami.8b15618
View details for Web of Science ID 000449887600014
View details for PubMedID 30300544
Dual purpose hafnium oxide nanoparticles offer imaging Streptococcus mutans dental biofilm and fight it In vivo via a drug free approach
2018; 181: 252–67
Manipulating the chiroptical properties at the nanoscale is of great importance in stereoselective reactions, enantioseparation, self-assembly, and biological phenomena. In recent years, carbon dots have garnered great attention because of their favorable properties such as tunable fluorescence, high biocompatibility, and facile, scalable synthetic procedures. Herein, we report for the first time the unusual behavior of cyclic amino acids on the surface of carbon dots prepared via microwave-based carbonization. Various amino acids were introduced on the surface of carbon dots via EDC/NHS conjugation at room temperature. Circular dichroism results revealed that although most of the surface conjugated amino acids can preserve their chirality on negatively charged, "bare" carbon dots, the "handedness" of cyclic α-amino acids can be flipped when covalently attached on carbon dots. Moreover, these chiroptical carbon dots were found to interact with the cellular membrane or its mimic in a highly selective manner due to their acquired asymmetric selectivity. A comprehensive inhibitor study was conducted to investigate the pathway of cellular trafficking of these carbon dots. Overall, it was concluded that the chirality of the amino acid on the surface of carbon dots could regulate many of the cellular processes.
View details for DOI 10.1021/acs.bioconjchem.8b00736
View details for Web of Science ID 000451496400045
View details for PubMedID 30352502
Fluorescence Detection of Bone Microcracks Using Monophosphonated Carbon Dots
ACS APPLIED MATERIALS & INTERFACES
2018; 10 (23): 19408–15
The removal of tenacious dental plaque is of paramount importance; however, early diagnosis can be a challenging task in dental clinics due to the limitations of current approaches, specifically X-ray-based techniques. We have approached this problem by integrating antibacterial properties and X-ray contrast enhancement in a single probe specific to colonies of Streptococcus mutans as the most predominant and carious oral bacteria. We report the synthesis of an inherently therapeutic polymeric silane conjugated hafnium oxide nanoparticles (Hf PS NPs). Using a high-affinity pathogen-selective peptide, the concept of molecularly targeted X-ray imaging of cariogenic pathogen S. mutans was demonstrated. Ex vivo studies using extracted human tooth demonstrated striking X-ray attenuation of NPs vs. tooth. Additionally, Hf PS NPs exhibited significant bactericidal properties against cariogenic pathogen. Electron microscopy revealed that the antibacterial activity occurred via a 'latch and kill' mechanism. Mechanistic studies determined that these NPs fragmented bacterial DNA components to exert their antimicrobial effect. Importantly, Hf PS NPs effectively inhibited the growth of a mature biofilm on an ex vivo human tooth model. Finally, the NPs were applied to the rodent model of dental biofilm. Topical administration of the Hf PS NPs for 8 days (1X daily) could effectively attenuate the S. mutans biofilm challenge. This report is the first of its kind to demonstrate that HfO2-based NPs can be used for simultaneous diagnosis and antibacterial treatment without requiring an additional drug.
View details for DOI 10.1016/j.biomaterials.2018.07.053
View details for Web of Science ID 000447111200018
View details for PubMedID 30096560
Copper-Catalyzed Syntheses of Pyrene-Pyrazole Pharmacophores and Structure Activity Studies for Tubulin Polymerization
2018; 3 (6): 6378–87
Phosphonated compounds, in particular, bisanalogs are widely applied in clinical settings for the treatment of severe bone turnovers and recently as imaging probes when conjugated with organic fluorophores. Herein, we introduce a bone seeking luminescent probe that shows a high binding affinity toward bone minerals based on monophosphonated carbon dots (CDs). Spheroidal CDs tethered with PEG monophosphates are synthesized in a one-pot hydrothermal method and are physicochemically characterized, where the retention of phosphonates is confirmed by 13P NMR and X-ray photoelectron spectroscopy. Interestingly, the high abundance of multiple monodentate phosphonates exhibited strong binding to hydroxyapatite, the main bone mineral constituent. The remarkable optophysical properties of monophosphonated CDs were confirmed in an ex vivo model of the bovine cortical bone where the imaging feasibility of microcracks, which are calcium-rich regions, was demonstrated. The in vivo studies specified the potential application of monophosphonated CDs for imaging when injected intramuscularly. The biodigestible nature and cytocompatibility of the probe presented here obviate the demand for a secondary fluorophore, while offering a nanoscale strategy for bone targeting and can eventually be employed for potential bone therapy in the future.
View details for DOI 10.1021/acsami.8b03727
View details for Web of Science ID 000435525100014
View details for PubMedID 29757601
Revisiting Polyarenes and Related Molecules: An Update of Synthetic Approaches and Structure-Activity-Mechanistic Correlation for Carcinogenesis
2018; 18 (6): 619–58
Tubulin polymerization is critical in mitosis process, which regulates uncontrolled cell divisions. Here, we report a new class of pyrene-pyrazole pharmacophore (PPP) for targeting microtubules. Syntheses of seven pyrenyl-substituted pyrazoles with side-chain modification at N-1 and C-3 positions of the pyrazole ring were accomplished from alkenyl hydrazones via C-N dehydrogenative cross-coupling using copper catalyst under aerobic condition. Tubulin polymerization with PPPs was investigated using docking and biological tools to reveal that these ligands are capable of influencing microtubule polymerization and their interaction with α-, β-tubulin active binding sites, which are substituent specific. Furthermore, cytotoxicity response of these PPPs was tested on cancer cells of different origin, such as MCF-7, MDA-MB231, and C32, and also noncancerous normal cells, such as MCF-10A. All newly synthesized PPPs showed excellent anticancer activities. The anticancer activities and half-maximal inhibitory concentration (IC50) values of all PPPs across different cancer cell lines (MCF-7, MDA-MB231, and C32) have been demonstrated. 1,3-Diphenyl-5-(pyren-1-yl)-1H-pyrazole was found to be best among all other PPPs in killing significant population of all of the cancerous cell with IC50 values 1 ± 0.5, 0.5 ± 0.2, and 5.0 ± 2.0 μM in MCF-7, MDA-MB231, and C32 cells, respectively.
View details for DOI 10.1021/acsomega.8b00320
View details for Web of Science ID 000436340500052
View details for PubMedID 30221233
View details for PubMedCentralID PMC6130796
Surface chemistry of carbon nanoparticles functionally select their uptake in various stages of cancer cells
2017; 10 (10): 3269–84
alpha-Amino Acid Rich Photophytonic Nanoparticles of Algal Origin Serendipitously Reveal Antimigratory Property against Cancer
ACS APPLIED MATERIALS & INTERFACES
2017; 9 (25): 21147–54
A major proportion of basic cause for human cancer has been linked to widespread environmental pollutants including analogs of polyarenes. Search of an effective therapy can be started with the understanding of the generation of such "carcinogens" and their biological interactions. This review is to discuss the syntheses, structural activities, mechanistic and biological studies of polyarenes such as polycyclic aromatic hydrocarbons (PAHs), polycyclic azaarenes (PAAs) and their thia-analogs (PASH). It also summarizes the mechanism of mutagenicity and tumorigenicity via metabolic interventions producing diol epoxide complexes and eventually formation of DNA adducts. It suggests that inhibition of oxidative reactions and formation of diols and epoxides and unspecific intracellular activation of cytochrome P450 enzymes could be approaches in therapy against such mutagenicity and tumorigenicity. Thus, this review reflects that understanding of molecular mechanisms and activations along with a clinical and translational medicine approach would require achieving both prevention and treatment of this atrocity.
View details for DOI 10.1002/tcr.201700110
View details for Web of Science ID 000435815200005
View details for PubMedID 29465807
3D-Printed Multidrug-Eluting Stent from Graphene-Nanoplatelet-Doped Biodegradable Polymer Composite
ADVANCED HEALTHCARE MATERIALS
2017; 6 (11)
Spheroidal nanoparticles of algal ("phytonic") origin were synthesized and composed of carbonaceous architectures and surface-rich oxygenated functional groups. Nanoparticles were negatively charged and efficiently luminescent after ultraviolet-range excitation and called as "photophytonic" nanoparticles. A multitude of analytical techniques confirmed the rich profusion of hydroxyl, carboxylate, and amines at the nanoscale, while spectroscopic investigation indicated the presence of α-amines, a signature functionality present in amino acids. Confirmed via a series of biological assays, i.e., growth regression, antimigration, and protein-regression studies, photophytonic nanoparticles serendipitously revealed remarkable anticancer activity against various stages of breast cancer cells, barring the need for an encapsulated drug. We report that nanoparticles derived from algal biomass exhibit intrinsic antimigratory properties against cancer, likely due to the rich abundance of α-amino acids.
View details for DOI 10.1021/acsami.7b04962
View details for Web of Science ID 000404807200012
View details for PubMedID 28581711
Functional carbon nanodots for multiscale imaging and therapy
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
2017; 9 (3)
Patients with percutaneous coronary intervention generally receive either bare metal stents or drug-eluting stents to restore the normal blood flow. However, due to the lack of stent production with an individual patient in mind, the same level of effectiveness may not be possible in treating two different clinical scenarios. This study introduces for the first time the feasibility of a patient-specific stenting process constructed from direct 3D segmentation of medical images using direct 3D printing of biodegradable polymer-graphene composite with dual drug incorporation. A biodegradable polymer-carbon composite is prepared doped with graphene nanoplatelets to achieve controlled release of combinatorics as anticoagulation and antirestenosis agents. This study develops a technology prototyped for personalized stenting. An in silico analysis is performed to optimize the stent design for printing and its prediction of sustainability under force exerted by coronary artery or blood flow. A holistic approach covering in silico to in situ-in vivo establishes the structural integrity of the polymer composite, its mechanical properties, drug loading and release control, prototyping, functional activity, safety, and feasibility of placement in coronary artery of swine.
View details for DOI 10.1002/adhm.201700008
View details for Web of Science ID 000402881700008
View details for PubMedID 28322012
Nanosalina: A Tale of Saline-Loving Algae from the Lake's Agony to Cancer Therapy
ACS APPLIED MATERIALS & INTERFACES
2017; 9 (13): 11528–36
As an emerging class of carbon nanomaterials, carbon dots (CDs) have garnered many researchers' interests in the past decade due to their excellent biocompatibility, replete surface functional groups, water dispersibility, and unique photoluminescence. These extraordinary properties have opened new avenues for their advanced application in cell labeling, bioimaging, drug delivery, sensors, and energy-related devices. In this paper, we critically review recent advances in the synthetic strategies and the application of CDs for biological purposes, specifically, imaging and therapy. Finally, a perspective has been given on the potential challenges facing the translation of these materials from the bench to the market. WIREs Nanomed Nanobiotechnol 2017, 9:e1436. doi: 10.1002/wnan.1436 For further resources related to this article, please visit the WIREs website.
View details for DOI 10.1002/wnan.1436
View details for Web of Science ID 000399348400004
View details for PubMedID 27791335
Real-Time Monitoring of Post-Surgical and Post-Traumatic Eye Injuries Using Multilayered Electrical Biosensor Chip
ACS APPLIED MATERIALS & INTERFACES
2017; 9 (10): 8609–22
The nanoparticles (NPs) that contain the therapeutic agent within themselves without further modifications can be coined as "self-therapeutic" NPs. The development of these agents especially when derived from natural resources can lead to a paradigm shift in the field of cancer nanotechnology as they can immensely facilitate the complex chemistry procedures and the follow up biological complications. Herein, we demonstrate that inherently therapeutic NPs "integrating" β-carotene can be synthesized from Dunaliella salina microalgae in a single step without complicated chemistry. The facile synthesis involved microwave irradiation of aqueous suspension of algae which resulted in water dispersible NPs with hydrodynamic diameter of ∼80 nm. Subsequently, extensive physiochemical characterizations were performed to confirm the integrity of the particles. The pro-oxidant activities of the integrated β-carotene were triggered by photoexcitation under UV lamp (362 nm). It was demonstrated that after UV exposure, the C32 human melanoma cells incubated with NPs experienced extensive cell death as opposed to nonilluminated samples. Further cellular analysis revealed that the significant reactive oxygen species (ROS) and in particular singlet oxygen were responsible for the cells' damage while the mode of cell death was dominated by apoptosis. Moreover, detailed endocytic inhibition studies specified that UV exposure affected NPs' cellular uptake mechanism. These inherently therapeutic NPs can open new avenues for melanoma cancer treatment via ROS generation in vitro.
View details for DOI 10.1021/acsami.7b01483
View details for Web of Science ID 000398764100024
View details for PubMedID 28291324
Macromolecularly "Caged" Carbon Nanoparticles for Intracellular Trafficking via Switchable Photoluminescence
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2017; 139 (5): 1746–49
Lack of current techniques for the early monitoring of bleb leaks and other post-traumatic or post-surgical ocular injury has posed an unmet clinical need for the development of new techniques. Present evaluation techniques use either subjective or nonquantitative approaches. At present, there are no FDA approved ocular devices that can directly measure ascorbic acid (AA) concentration levels for both tear film (TF) and aqueous humor (AH) at point-of-care (POC) level. Toward this aim, we present a novel POC quantitative assay, called the ocular biosensor device, which can be used to evaluate the integrity of the anterior surface of the eye by measuring the concentration of AA in TF and AH. Herein, we utilize a novel scientific engineering approach for the development of a disposable paper based POC ocular biosensor strip. A grafted poly(styrene)-block-poly(acrylic acid) (PS-b-PAA) and graphene platelet composite with contour based μ-electrodes design (CBμE) exhibit a highly sensitive platform to perform electrochemical immunosensing technique to study clinical samples that have small volumes like tear fluid. Samples used in this study were collected clinically from subjects undergoing therapeutic anterior chamber paracentesis. The proposed biosensor reports the level of AA concentration on an electronic screen, making the results easy to read, efficient, and reliable.
View details for DOI 10.1021/acsami.7b01675
View details for Web of Science ID 000396801200020
View details for PubMedID 28207238
Hyperspectral Imaging Offers Visual and Quantitative Evidence of Drug Release from Zwitterionic-Phospholipid-Nanocarbon When Concurrently Tracked in 3D Intracellular Space
ADVANCED FUNCTIONAL MATERIALS
2016; 26 (44): 8031–41
Defined Host-Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer
2016; 12 (42): 5845–61
Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counterionic macromolecular caging and decaging at the nanoscale. A negatively charged uncoated, "bare" CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant molecules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies. Results indicated for the first time that luminescence switchable CNPs can be synthesized for efficient intracellular tracking. This study further supports the origin of photoluminescence in CNP as a surface phenomenon correlated a function of characteristic charged macromolecules.
View details for DOI 10.1021/jacs.6b11595
View details for Web of Science ID 000393848400010
View details for PubMedID 28106386
Pro-haloacetate Nanoparticles for Efficient Cancer Therapy via Pyruvate Dehydrogenase Kinase Modulation
2016; 6: 28196
Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbituril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host-guest chemistry between cucurbituril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host-guest chemistry of niclosamide and cucurbituril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF-7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT-3 phosphorylation. Overall, the host-guest chemistry on nanocarbon acts as a novel arsenal for STAT-3 inhibition.
View details for DOI 10.1002/smll.201601161
View details for Web of Science ID 000389403900007
View details for PubMedID 27545321
View details for PubMedCentralID PMC5542878
Physicochemical and antibacterial properties of chitosan-polyvinylpyrrolidone films containing self-organized graphene oxide nanolayers
JOURNAL OF APPLIED POLYMER SCIENCE
2016; 133 (11)
Carotenoid Nanovector for Efficient Therapeutic Gene Knockdown of Transcription Factor FOXC1 in Liver Cancer
2016; 27 (3): 594–603
Anticancer agents based on haloacetic acids are developed for inhibition of pyruvate dehydrogenase kinase (PDK), an enzyme responsible for reversing the suppression of mitochondria-dependent apoptosis. Through molecular docking studies mono- and dihaloacetates are identified as potent PDK2 binders and matched their efficiency with dichloroacetic acid. In silico screening directed their conversion to phospholipid prodrugs, which were subsequently self-assembled to pro-haloacetate nanoparticles. Following a thorough physico-chemical characterization, the functional activity of these novel agents was established in wide ranges of human cancer cell lines in vitro and in vivo in rodents. Results indicated that the newly explored PDK modulators can act as efficient agent for cancer regression. A Pyruvate dehydrogenase (PDH) assay mechanistically confirmed that these agents trigger their activity through the mitochondria-dependent apoptosis.
View details for DOI 10.1038/srep28196
View details for Web of Science ID 000378124300002
View details for PubMedID 27323896
View details for PubMedCentralID PMC4914936
(-)/(+)-Sparteine induced chirally-active carbon nanoparticles for enantioselective separation of racemic mixtures
2016; 52 (47): 7513–16
Transcription factor FOXC1 has been implicated to play a critical role in hepatocellular carcinoma (HCC) progression, but targeting FOXC1 for therapeutic benefit remains a challenge owing to its location inside the cell nucleus. Herein we report successful therapeutic gene knockdown of transcription factor FOXC1 in liver cancer cells through efficient delivery of siFOXC1 using novel carotenoid functionalized dendritic nanoparticles (CDN). This delivery system also displayed a markedly reduced toxicity profile compared to a standard siRNA transfection agent. We were able to achieve ∼90% FOXC1 knockdown using the CDN-siFOXC1 complex. Additionally, it was found to have ∼18% greater delivery efficiency compared to treatments with particles which have no carotenoid tagging, thereby emphasizing the role of carotenoid mediated cell internalization in the efficient delivery of CDN-siFOXC1 complex in liver cancer cells.
View details for DOI 10.1021/acs.bioconjchem.5b00601
View details for Web of Science ID 000372478600013
View details for PubMedID 26720420
Personalized Medicine with a Nanochemistry Twist: Nanomedicine
PERSONALIZED MEDICINE WITH A NANOCHEMISTRY TWIST: NANOMEDICINE
2016; 20: 1–133
Development of Chitosan/Bacterial Cellulose Composite Films Containing Nanodiamonds as a Potential Flexible Platform for Wound Dressing
2015; 8 (9): 6401–18
Chiral carbon nanoparticles (CCNPs) were developed by surface passivation using the chiral ligand (-)-sparteine or (+)-sparteine (denoted (-)-SP/CNP and (+)-SP/CNP, respectively). The chirality of the prepared CCNPs was demonstrated by circular dichroism and polarimetry and employed as an enantioselective separation platform for representative racemic mixtures.
View details for DOI 10.1039/c6cc02525k
View details for Web of Science ID 000378003800020
View details for PubMedID 27214647
On the effect of cooling rate during melt spinning of FINEMET ribbons
2013; 5 (16): 7520–27
Chitosan/bacterial cellulose composite films containing diamond nanoparticles (NDs) with potential application as wound dressing are introduced. Microstructural studies show that NDs are uniformly dispersed in the matrix, although slight agglomeration at concentrations above 2 wt % is seen. Fourier transform infrared spectroscopy reveals formation of hydrogen bonds between NDs and the polymer matrix. X-ray diffraction analysis indicates reduced crystallinity of the polymer matrix in the presence of NDs. Approximately 3.5-fold increase in the elastic modulus of the composite film is obtained by the addition of 2 wt % NDs. The results of colorimetric analysis show that the composite films are transparent but turn to gray-like and semitransparent at high ND concentrations. Additionally, a decrease in highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) gap is also seen, which results in a red shift and higher absorption intensity towards the visible region. Mitochondrial activity assay using L929 fibroblast cells shows that the nanocomposite films are biocompatible (>90%) after 24 h incubation. Multiple lamellapodia and cell-cell interaction are shown. The results suggest that the developed films can potentially be used as a flexible platform for wound dressing.
View details for DOI 10.3390/ma8095309
View details for Web of Science ID 000362640300008
View details for PubMedID 28793571
View details for PubMedCentralID PMC5512916
The effect of quenching wheel speed on the structure and Curie temperature of Fe73.5Si13.5B9Nb3Cu1 alloy has been investigated using X-ray diffraction, differential scanning calorimetry, transition electron microscopy and a SQUID magnetometer. Ribbons were melt-spun at different wheel speeds and then were annealed to nucleate nano crystals embedded in the amorphous matrix. The results indicated that the thickness of the ribbons was inversely proportional to the wheel speed following the power law of the type t∝V(s)(-1.231). DSC and XRD results showed that at higher wheel speeds the greater potential energy triggers the formation of Fe (Si) crystallites and thus, increases the crystallinity. TEM observations confirmed the presence of an α-Fe (Si) phase with ∼11 nm crystallite size in the amorphous matrix of annealed ribbons. Special emphasis was placed on the effect of the quenching wheel speed on the Curie temperature during the measurements. To this end, the magnetization variations versus temperature were studied before and after annealing. It was found that increasing the wheel speed results in the reduction of the Curie temperature in as-spun ribbons. Moreover, the Curie temperature of the intergranular amorphous region in the annealed ribbons was at least 80 °C higher than that of corresponding amorphous phase in as-spun ribbons due to exchange interaction penetration of the adjacent Fe (Si) crystallites and relaxation processes.
View details for DOI 10.1039/c3nr01213a
View details for Web of Science ID 000322315600054
View details for PubMedID 23832313