Light-Induced Wavelength Dependent Self Assembly Process for Targeted Synthesis of Phase Stable 1D Nanobelts and 2D Nanoplatelets of CsPbI3 Perovskites.

Despite black cubic phase α-CsPbI3 nanocrystals having an ideal bandgap of 1.73 eV for optoelectronic applications, the phase transition from α-CsPbI3 to non-perovskite yellow δ-CsPbI3 phase at room temperature remains a major obstacle for commercial applications. Since γ-CsPbI3 is thermodynamically stable with a bandgap of 1.75 eV, which has great potential for photovoltaic applications, herein we report a conceptually new method for the targeted design of phase stable and near unity photoluminescence quantum yield (PLQY) two-dimensional (2D) γ-CsPbI3 nanoplatelets (NPLs) and one-dimensional (1D) γ-CsPbI3 nanobelts (NBs) by wavelength dependent light-induced assembly of CsPbI3 cubic nanocrystals. This article demonstrates for the first time that by varying the excitation wavelengths, one can design air stable desired 2D nanoplatelets or 1D nanobelts selectively. Our experimental finding indicates that 532 nm green light-driven self-assembly produces phase stable and highly luminescent γ-CsPbI3 NBs from CsPbI3 nanocrystals. Moreover, we show that a 670 nm red light-driven self-assembly process produces stable and near unity PLQY γ-CsPbI3 NPLs. Systematic time-dependent microscopy and spectroscopy studies on the morphological evolution indicates that the electromagnetic field of light triggered the desorption of surface ligands from the nanocrystal surface and transformation of crystallographic phase from α to γ. Detached ligands played an important role in determining the morphologies of final structures of NBs and NPLs from nanocrystals via oriented attachment along the [110] direction initially and then the [001] direction. In addition, XRD and fluorescence imaging data indicates that both NBs and NPLs exhibit phase stability for more than 60 days in ambient conditions, whereas the cubic phase α-CsPbI3 nanocrystals are not stable for even 3 days. The reported light driven synthesis provides a simple and versatile approach to obtain phase pure CsPbI3 for possible optoelectronic applications.

Human ACE2 Peptide-Attached Plasmonic-Magnetic Heterostructure for Magnetic Separation, Surface Enhanced Raman Spectroscopy Identification, and Inhibition of Different Variants of SARS-CoV-2 Infections.

The emergence of Alpha, Beta, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for several million deaths up to now. Because of the huge amount of vaccine escape mutations in the spike (S) protein for different variants, the design of material for combating SARS-CoV-2 is very important for our society. Herein, we report on the design of a human angiotensin converting enzyme 2 (ACE2) peptide-conjugated plasmonic-magnetic heterostructure, which has the capability for magnetic separation, identification via surface enhanced Raman spectroscopy (SERS), and inhibition of different variant SARS-CoV-2 infections. In this work, plasmonic-magnetic heterostructures were developed using the initial synthesis of polyethylenimine (PEI)-coated Fe3O4-based magnetic nanoparticles, and then gold nanoparticles (GNPs) were grown onto the surface of the magnetic nanoparticles. Experimental binding data between ACE2-conjugated plasmonic-magnetic heterostructures and spike-receptor-binding domain (RBD) show that the Omicron variant has maximum binding ability, and it follows Alpha < Beta < Gamma < Delta < Omicron. Our finding shows that, due to the high magnetic moment (specific magnetization 40 emu/g), bioconjugated heterostructures are capable of effective magnetic separation of pseudotyped SARS-CoV-2 bearing the Delta variant spike from an infected artificial nasal mucus fluid sample using a simple bar magnet. Experimental data show that due to the formation of huge "hot spots" in the presence of SARS-CoV-2, Raman intensity for the 4-aminothiolphenol (4-ATP) Raman reporter was enhanced sharply, which has been used for the identification of separated virus. Theoretical calculations using finite-difference time-domain (FDTD) simulation indicate that, due to the "hot spots" formation, a six orders of magnitude Raman enhancement can be observed. A concentration-dependent inhibition efficiency investigation using a HEK293T-human cell line indicates that ACE2 peptide-conjugated plasmonic-magnetic heterostructures have the capability of complete inhibition of entry of different variants and original SARS-CoV-2 pseudovirions into host cells.

Second-Order Photoinduced Reflectivity for Retrieval of the Dynamics in Plasmonic Nanostructures.

Measuring the change in reflectivity (ΔR) using the traditional pump-probe approach can monitor photoinduced ultrafast dynamics in matter, yet relating these dynamic to physical processes for complex systems is not unique. By applying a simple modification to the classical pump-probe technique, we simultaneously measure both the first and second order of ΔR. These additional data impose new constraints on the interpretation of the underlying ultrafast dynamics. In the first application of the approach, we probe the dynamics induced by a pump laser on the local-surface plasmon resonance (LSPR) in gold nanoantennas. Measurements of ΔR over several picoseconds and a wide range of probe wavelengths around the LSPR peak are followed by data fitting using the two-temperature model. The constraints, imposed by the second-order data, lead us to modify the model and force us to include the contribution of nonthermalized electrons in the early stages of the dynamics.

Bio-Conjugated Magnetic-Fluorescence Nanoarchitectures for the Capture and Identification of Lung-Tumor-Derived Programmed Cell Death Lighand 1-Positive Exosomes.

As per the American Cancer Society, lung cancer is the leading cause of cancer-related death worldwide. Since the accumulation of exosomal programmed cell death ligand 1 (PD-L1) is associated with therapeutic resistance in programmed cell death 1 (PD-1) and PD-L1 immunotherapy, tracking PD-L1-positive (PD-L1 (+)) exosomes is very important for predicting anti-PD-1 and anti-PD-L1 therapy for lung cancer. Herein, we report the design of an anti-PD-L1 monoclonal antibody-conjugated magnetic-nanoparticle-attached yellow fluorescent carbon dot (YFCD) based magnetic-fluorescence nanoarchitecture for the selective separation and accurate identification of PD-L1-expressing exosomes. In this work, photostable YFCDs with a good photoluminescence quantum yield (23%) were synthesized by hydrothermal treatment. In addition, nanoarchitectures with superparamagnetic (28.6 emu/g), biocompatible, and selective bioimaging capabilities were developed by chemically conjugating the anti-PD-L1 antibody and YFCDs with iron oxide nanoparticles. Importantly, using human non-small-cell lung cancer H460 cells lines, which express a high amount of PD-L1 (+) exosomes, A549 lung cancer cells lines, which express a low amount of PD-L1 (+) exosomes, and the normal skin HaCaT cell line, which does not express any PD-L1 (+) exosomes, we demonstrate that nanoarchitectures are capable of effectively separating and tracking PD-L1-positive exosomes simultaneously. Furthermore, as a proof-of-concept of clinical setting applications, a whole blood sample infected with PD-L1 (+) exosomes was analyzed, and our finding shows that this nanoarchitecture holds great promise for clinical applications.

Blocking SARS-CoV-2 Delta Variant (B.1.617.2) Spike Protein Receptor-Binding Domain Binding with the ACE2 Receptor of the Host Cell and Inhibiting Virus Infections Using Human Host Defense Peptide-Conjugated Graphene Quantum Dots.

The emergence of double mutation delta (B.1.617.2) variants has dropped vaccine effectiveness against SARS-CoV-2 infection. Although COVID-19 is responsible for more than 5.4 M deaths till now, more than 40% of infected individuals are asymptomatic carriers as the immune system of the human body can control the SARS-CoV-2 infection. Herein, we report for the first time that human host defense neutrophil α-defensin HNP1 and human cathelicidin LL-37 peptide-conjugated graphene quantum dots (GQDs) have the capability to prevent the delta variant virus entry into the host cells via blocking SARS-CoV-2 delta variant (B.1.617.2) spike protein receptor-binding domain (RBD) binding with host cells' angiotensin converting enzyme 2 (ACE2). Experimental data shows that due to the binding between the delta variant spike protein RBD and bioconjugate GQDs, in the presence of the delta variant spike protein, the fluorescence signal from GQDs quenched abruptly. Experimental quenching data shows a nonlinear Stern-Volmer quenching profile, which indicates multiple binding sites. Using the modified Hill equation, we have determined n = 2.6 and the effective binding affinity 9 nM, which is comparable with the ACE2-spike protein binding affinity (8 nM). Using the alpha, beta, and gamma variant spike-RBD, experimental data shows that the binding affinity for the delta B.1.617.2 variant is higher than those for the other variants. Further investigation using the HEK293T-human ACE2 cell line indicates that peptide-conjugated GQDs have the capability for completely inhibiting the entry of delta variant SARS-CoV-2 pseudovirions into host cells via blocking the ACE2-spike protein binding. Experimental data shows that the inhibition efficiency for LL-37 peptide- and HNP1 peptide-attached GQDs are much higher than that of only one type of peptide-attached GQDs.

Microbial decolorization and detoxification of emerging environmental pollutant: Cosmetic hair dyes.

Since the usage of hair dyes has increased in recent time, the removal of residual dye from environment is also an emerging issue. Hair dye contains mixture of chemicals including genotoxic chemical, p-phenylenediamine (p-PD or PPD). The present study reports bioremediation of hair dye using bacteria isolated from saloon effluent. Sugarcane bagasse powder (SBP) was used as a source of nutrient and surface for bacterial growth. The 16S rDNA sequencing confirmed the isolate as Enterobacter cloacae which was designated as DDB I. The decolourization of dye was studied using UV-vis spectrophotometer. The detoxification study was conducted on microbes isolated from fresh ponds using well diffusion assay. The 1mg/ml of dye was effectively decolourised within 18h of DDB I treatment in the minimal medium containing 30mg/ml of SBP.

Nanoarchitecture Based SERS for Biomolecular Fingerprinting and Label-Free Disease Markers Diagnosis.

Surface-enhanced Raman spectroscopy (SERS) fingerprinting is highly promising for identifying disease markers from complex mixtures of clinical sample, which has the capability to take medical diagnoses to the next level. Although vibrational frequency in Raman spectra is unique for each biomolecule, which can be used as fingerprint identification, it has not been considered to be used routinely for biosensing due to the fact that the Raman signal is very weak. Contemporary SERS has been demonstrated to be an excellent analytical tool for practical label-free sensing applications due its ability to enhance Raman signals by factors of up to 108-1014 orders of magnitude. Although SERS was discovered more than 40 years ago, its applications are still rare outside the spectroscopy community and it is mainly due to the fact that how to control, manipulate and amplify light on the "hot spots" near the metal surface is in the infancy stage. In this Account, we describe our contribution to develop nanoachitecture based highly reproducible and ultrasensitive detection capability SERS platform via low-cost synthetic routes. Using one-dimensional (1D) carbon nanotube (CNT), two-dimensional (2D) graphene oxide (GO), and zero-dimensional (0D) plasmonic nanoparticle, 0D to 3D SERS substrates have been designed, which represent highly powerful platform for biological diagnosis. We discuss the major design criteria we have used to develop robust SERS substrate to possess high density "hot spots" with very good reproducibility. SERS enhancement factor for 3D SERS substrate is about 5 orders of magnitude higher than only plasmonic nanoparticle and more than 9 orders of magnitude higher than 2D GO. Theoretical finite-difference time-domain (FDTD) stimulation data show that the electric field enhancement |E|2 can be more than 2 orders of magnitude in "hot spots", which suggests that SERS enhancement factors can be greater than 104 due to the formation of high density "hot spots" in 3D substrate. Next, we discuss the utilization of nanoachitecture based SERS substrate for ultrasensitive and selective diagnosis of infectious disease organisms such as drug resistance bacteria and mosquito-borne flavi-viruses that cause significant health problems worldwide. SERS based "whole-organism fingerprints" has been used to identify infectious disease organisms even when they are so closely related that they are difficult to distinguish. The detection capability can be as low as 10 CFU/mL for methicillin-resistant Staphylococcus aureus (MRSA) and 10 PFU/mL for Dengue virus (DENV) and West Nile virus (WNV). After that, we introduce exciting research findings by our group on the applications of nanoachitecture based SERS substrate for the capture and fingerprint detection of rotavirus from water and Alzheimer's disease biomarkers from whole blood sample. The SERS detection limit for ß-amyloid (Aß proteins) and tau protein using 3D SERS platform is several orders of magnitude higher than the currently used technology in clinics. Finally, we highlight the promises, major challenges and prospect of nanoachitecture based SERS in biomedical diagnosis field.

Three-dimensional (3D) plasmonic hot spots for label-free sensing and effective photothermal killing of multiple drug resistant superbugs.

Drug resistant superbug infection is one of the foremost threats to human health. Plasmonic nanoparticles can be used for ultrasensitive bio-imaging and photothermal killing by amplification of electromagnetic fields at nanoscale "hot spots". One of the main challenges to plasmonic imaging and photothermal killing is design of a plasmonic substrate with a large number of "hot spots". Driven by this need, this article reports design of a three-dimensional (3D) plasmonic "hot spot"-based substrate using gold nanoparticle attached hybrid graphene oxide (GO), free from the traditional 2D limitations. Experimental results show that the 3D substrate has capability for highly sensitive label-free sensing and generates high photothermal heat. Reported data using p-aminothiophenol conjugated 3D substrate show that the surface enhanced Raman spectroscopy (SERS) enhancement factor for the 3D "hot spot"-based substrate is more than two orders of magnitude greater than that for the two-dimensional (2D) substrate and five orders of magnitude greater than that for the zero-dimensional (0D) p-aminothiophenol conjugated gold nanoparticle. 3D-Finite-Difference Time-Domain (3D-FDTD) simulation calculations indicate that the SERS enhancement factor can be greater than 104 because of the bent assembly structure in the 3D substrate. Results demonstrate that the 3D-substrate-based SERS can be used for fingerprint identification of several multi-drug resistant superbugs with detection limits of 5 colony forming units per mL. Experimental data show that 785 nm near infrared (NIR) light generates around two times more photothermal heat for the 3D substrate with respect to the 2D substrate, and allows rapid and effective killing of 100% of the multi-drug resistant superbugs within 5 minutes.

Designing a multicolor long range nanoscopic ruler for the imaging of heterogeneous tumor cells.

Tumor heterogeneity is one of the biggest challenges in cancer treatment and diagnosis. A multicolor optical ruler is essential to address the heterogeneous tumor cell complexity. Driven by this need, the current article reports the design of a multicolor long range nanoscopic ruler for screening tumor heterogeneity by accurately identifying epithelial cells and cancer stem cells (CSCs) simultaneously. A nanoscopic surface energy transfer (NSET) ruler has been developed using blue fluorescence polymer dots (PDs) and red fluorescence gold cluster dots (GCDs) as multicolor fluorescence donor and plasmonic gold nanoparticle (GNP) acts as an excellent acceptor. Reported experimental results demonstrated that the multicolor nanoscopic ruler's working window is above 35 nm distances, which is more than three times farther than that of Förster resonance energy transfer (FRET) distance limit. Theoretical modeling using Förster dipole-dipole coupling and dipole to nanoparticle surface energy transfer have been used to discuss the possible mechanism for multicolor nanoscopic ruler's long-range capability. Using RNA aptamers that are specific for the target cancer cells, experimental data demonstrate that the nanoscopic ruler can be used for screening epithelial and CSCs simultaneously from a whole blood sample with a detection capability of 10 cells per mL. Experimental data show that the nanoscopic ruler can distinguish targeted cells from non-targeted cells.

Development of Multifunctional Fluorescent-Magnetic Nanoprobes for Selective Capturing and Multicolor Imaging of Heterogeneous Circulating Tumor Cells.

Circulating tumor cells (CTC) are highly heterogeneous in nature due to epithelial-mesenchymal transition (EMT), which is the major obstacle for CTC analysis via "liquid biopsy". This article reports the development of a new class of multifunctional fluorescent-magnetic multicolor nanoprobes for targeted capturing and accurate identification of heterogeneous CTC. A facile design approach for the synthesis and characterization of bioconjugated multifunctonal nanoprobes that exhibit excellent magnetic properties and emit very bright and photostable multicolor fluorescence at red, green, and blue under 380 nm excitation is reported. Experimental data presented show that the multifunctional multicolor nanoprobes can be used for targeted capture and multicolor fluorescence mapping of heterogeneous CTC and can distinguish targeted CTC from nontargeted cells.

Multimodal Nonlinear Optical Imaging of Live Cells Using Plasmon-Coupled DNA-Mediated Gold Nanoprism Assembly.

Multiphoton excitation microscopy techniques are the emerging nonlinear optical (NLO) imaging methods to watch the biological world due its ability to penetrate deep into living tissues. Driven by the need to develop multimodal NLO imaging probe, current article reports the design of DNA-mediated gold nanoprisms assembly based optical antennas to enhance multiphoton imaging capability in biological II window. Reported experimental data show a unique way to enhance second harmonic generation (SHG) and two-photon fluorescence (TPF) properties by several orders of magnitudes via plasmon coupled organization into gold nanoprism assembly structures. Experimental and theoretical modeling data using finite difference time domain (FDTD) simulations indicate that huge enhancement of SHG and TPF properties are mainly due to the electric quadrupole contribution and electric field enhancement. Using 1100 nm biological II window light, reported results demonstrated that antibody conjugated assembly structures are capable of exhibiting highly selective and very bright multimodal SHG and TPF imaging of human Hep G2 liver cancer cells.

Analysis of cytotoxicity and genotoxicity on E. coli, human blood cells and Allium cepa suggests a greater toxic potential of hair dye.

Pharmaceuticals and personal care products (PPCPs) are among the most important emerging environmental contaminants in recent time. PPCPs include wide range of cosmetics, among which hair dyes, are immensely popular in modern society. However, impact of hair dye and its residual discharged to the environment in relation to human health and ecological imbalance have not been widely studied. Based on the result of initial survey among the group of populations of eastern India, three most popular and commonly used permanent hair dyes are selected. Working sample of dye is prepared as recommended on the instructions booklet of the hair dye. The effect of three dyes is studied on Escherichia coli, human red blood cells (RBC), white blood cells (WBC) and Allium cepa bulbs by growth inhibition, hemolysis, 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and A. cepa micronuclei assays respectively. The Lethal dose (LD) demonstrated significant differences among three dyes and the model systems. In vitro hemolytic assays performed on RBC, and MTT assays on WBC show the cytotoxic effects of hair dye. Significant growth inhibition of E. coli has also been noted. In addition, the root tips of A. cepa treated with the dye have shown major chromosomal abnormalities coupled with cell division retardation. Here low mitotic index confirm cell division retardation. Finally, results of in vitro studies of dye-DNA interactions demonstrate electrostatic interaction. Combing all these results it confirms that hair dyes are cytotoxic and may cause mutagenic effect on living cells irrespective of microbes, plant and animal system.

Hybrid Theranostic Platform for Second Near-IR Window Light Triggered Selective Two-Photon Imaging and Photothermal Killing of Targeted Melanoma Cells.

Despite advances in the medical field, even in the 21st century cancer is one of the leading causes of death for men and women in the world. Since the second near-infrared (NIR) biological window light between 950 and 1350 nm offers highly efficient tissue penetration, the current article reports the development of hybrid theranostic platform using anti-GD2 antibody attached gold nanoparticle (GNP) conjugated, single-wall carbon nanotube (SWCNT) for second near-IR light triggered selective imaging and efficient photothermal therapy of human melanoma cancer cell. Reported results demonstrate that due to strong plasmon-coupling, two-photon luminescence (TPL) intensity from theranostic GNP attached SWCNT materials is 6 orders of magnitude higher than GNP or SWCNT alone. Experimental and FDTD simulation data indicate that the huge enhancement of TPL intensity is mainly due to strong resonance enhancement coupled with the stronger electric field enhancement. Due to plasmon coupling, the theranostic material serves as a local nanoantennae to enhance the photothermal capability via strong optical energy absorption. Reported data show that theranostic SWCNT can be used for selective two-photon imaging of melanoma UACC903 cell using 1100 nm light. Photothermal killing experiment with 1.0 W/cm(2) 980 nm laser light demonstrates that 100% of melanoma UACC903 cells can be killed using theranostic SWCNT bind melanoma cells after just 8 min of exposure. These results demonstrate that due to plasmon coupling, the theranostic GNP attached SWCNT material serves as a two-photon imaging and photothermal source for cancer cells in biological window II.

Antimicrobial Peptide-Conjugated Graphene Oxide Membrane for Efficient Removal and Effective Killing of Multiple Drug Resistant Bacteria.

According to the World Health Organization (WHO), multiple drug-resistant (MDR) bacterial infection is a top threat to human health. Since bacteria evolve to resist antibiotics faster than scientists can develop new classes of drugs, the development of new materials which can be used, not only for separation, but also for effective disinfection of drug resistant pathogens is urgent. Driven by this need, we report for the first time the development of a nisin antimicrobial peptide conjugated, three dimensional (3D) porous graphene oxide membrane for identification, effective separation, and complete disinfection of MDR methicillin-resistant Staphylococcus aureus (MRSA) pathogens from water. Experimental data show that due to the size differences, MRSA is captured by the porous membrane, allowing only water to pass through. SEM, TEM, and fluorescence images confirm that pathogens are captured by the membrane. RT-PCR data with colony counting indicate that almost 100% of MRSA can be removed and destroyed from the water sample using the developed membrane. Comparison of MDR killing data between nisin alone, the graphene oxide membrane and the nisin attached graphene oxide membrane demonstrate that the nisin antimicrobial peptide attached graphene oxide membrane can dramatically enhance the possibility of destroying MRSA via a synergestic effect due to the multimodal mechanism.

Bio-Conjugated CNT-Bridged 3D Porous Graphene Oxide Membrane for Highly Efficient Disinfection of Pathogenic Bacteria and Removal of Toxic Metals from Water.

More than a billion people lack access to safe drinking water that is free from pathogenic bacteria and toxic metals. The World Health Organization estimates several million people, mostly children, die every year due to the lack of good quality water. Driven by this need, we report the development of PGLa antimicrobial peptide and glutathione conjugated carbon nanotube (CNT) bridged three-dimensional (3D) porous graphene oxide membrane, which can be used for highly efficient disinfection of Escherichia coli O157:H7 bacteria and removal of As(III), As(V), and Pb(II) from water. Reported results demonstrate that versatile membrane has the capability to capture and completely disinfect pathogenic pathogenic E. coli O157:H7 bacteria from water. Experimentally observed disinfection data indicate that the PGLa attached membrane can dramatically enhance the possibility of destroying pathogenic E. coli bacteria via synergistic mechanism. Reported results show that glutathione attached CNT-bridged 3D graphene oxide membrane can be used to remove As(III), As(V), and Pb(II) from water sample at 10 ppm level. Our data demonstrated that PGLa and glutathione attached membrane has the capability for high efficient removal of E. coli O157:H7 bacteria, As(III), As(V), and Pb(II) simultaneously from Mississippi River water.

Hybrid Graphene Oxide Based Plasmonic-Magnetic Multifunctional Nanoplatform for Selective Separation and Label-Free Identification of Alzheimer's Disease Biomarkers.

Despite intense efforts, Alzheimer's disease (AD) is one of the top public health crisis for society even at 21st century. Since presently there is no cure for AD, early diagnosis of possible AD biomarkers is crucial for the society. Driven by the need, the current manuscript reports the development of magnetic core-plasmonic shell nanoparticle attached hybrid graphene oxide based multifunctional nanoplatform which has the capability for highly selective separation of AD biomarkers from whole blood sample, followed by label-free surface enhanced Raman spectroscopy (SERS) identification in femto gram level. Experimental ELISA data show that antibody-conjugated nanoplatform has the capability to capture more than 98% AD biomarkers from the whole blood sample. Reported result shows that nanoplatform can be used for SERS "fingerprint" identification of ß-amyloid and tau protein after magnetic separation even at 100 fg/mL level. Experimental results indicate that very high sensitivity achieved is mainly due to the strong plasmon-coupling which generates huge amplified electromagnetic fields at the "hot spot". Experimental results with nontargeted HSA protein, which is one of the most abundant protein components in cerebrospinal fluid (CSF), show that multifunctional nanoplatform based AD biomarkers separation and identification is highly selective.

Multifunctional biocompatible graphene oxide quantum dots decorated magnetic nanoplatform for efficient capture and two-photon imaging of rare tumor cells.

Circulating tumor cells (CTCs) are extremely rare cells in blood containing billions of other cells. The selective capture and identification of rare cells with sufficient sensitivity is a real challenge. Driven by this need, this manuscript reports the development of a multifunctional biocompatible graphene oxide quantum dots (GOQDs) coated, high-luminescence magnetic nanoplatform for the selective separation and diagnosis of Glypican-3 (GPC3)-expressed Hep G2 liver cancer tumor CTCs from infected blood. Experimental data show that an anti-GPC3-antibody-attached multifunctional nanoplatform can be used for selective Hep G2 hepatocellular carcinoma tumor cell separation from infected blood containing 10 tumor cells/mL of blood in a 15 mL sample. Reported data indicate that, because of an extremely high two-photon absorption cross section (40530 GM), an anti-GPC3-antibody-attached GOQDs-coated magnetic nanoplatform can be used as a two-photon luminescence platform for selective and very bright imaging of a Hep G2 tumor cell in a biological transparency window using 960 nm light. Experimental results with nontargeted GPC3(-) and SK-BR-3 breast cancer cells show that multifunctional-nanoplatform-based cell separation, followed by two-photon imaging, is highly selective for Hep G2 hepatocellular carcinoma tumor cells.

Aptamer-conjugated graphene oxide membranes for highly efficient capture and accurate identification of multiple types of circulating tumor cells.

Tumor metastasis is responsible for 1 in 4 deaths in the United States. Though it has been well-documented over past two decades that circulating tumor cells (CTCs) in blood can be used as a biomarker for metastatic cancer, there are enormous challenges in capturing and identifying CTCs with sufficient sensitivity and specificity. Because of the heterogeneous expression of CTC markers, it is now well understood that a single CTC marker is insufficient to capture all CTCs from the blood. Driven by the clear need, this study reports for the first time highly efficient capture and accurate identification of multiple types of CTCs from infected blood using aptamer-modified porous graphene oxide membranes. The results demonstrate that dye-modified S6, A9, and YJ-1 aptamers attached to 20-40 µm porous garphene oxide membranes are capable of capturing multiple types of tumor cells (SKBR3 breast cancer cells, LNCaP prostate cancer cells, and SW-948 colon cancer cells) selectively and simultaneously from infected blood. Our result shows that the capture efficiency of graphene oxide membranes is ~95% for multiple types of tumor cells; for each tumor concentration, 10 cells are present per milliliter of blood sample. The selectivity of our assay for capturing targeted tumor cells has been demonstrated using membranes without an antibody. Blood infected with different cells also has been used to demonstrate the targeted tumor cell capturing ability of aptamer-conjugated membranes. Our data also demonstrate that accurate analysis of multiple types of captured CTCs can be performed using multicolor fluorescence imaging. Aptamer-conjugated membranes reported here have good potential for the early diagnosis of diseases that are currently being detected by means of cell capture technologies.

Long-range two-photon scattering spectroscopy ruler for screening prostate cancer cells.

Optical rulers have served as a key tool for scientists from different disciplines to address a wide range of biological activity. Since the optical window of state of the art FRET rulers is limited to a 10 nm distance, developing long range optical rulers is very important to monitor real life biological processes. Driven by this need, the current manuscript reports for the first time the design of long-range two-photon scattering (TPS) spectroscopy rulers using gold nano-antenna separated by a bifunctional rigid double strand DNA molecule, which controls the spectroscopy ruler length. Reported data demonstrate that the TPS spectroscopy ruler's working window is a within a 25 nm distance, which is more than twice that of well recognized FRET optical ruler. A possible mechanism for the two-photon spectroscopy ruler's long range capability have been discussed using angle-resolved TPS measurement and FDTD simulations. Solution-phase experimental data demonstrated that a long-range TPS ruler using A9 aptamer can be used for the screening of prostate-specific membrane antigen (PSMA) (+) prostate cancer cells even at 5 cells per mL level. Reported result with PSMA (-) normal skin HaCaT cells indicate that TPS ruler based assay has the capability to enable distinction from non-targeted cell lines. Ultimately, the long range TPS ruler can be used towards better understanding of chemical and biological processes.

Aptamer-conjugated theranostic hybrid graphene oxide with highly selective biosensing and combined therapy capability.

Cancer is a life-threatening disease, which is rapidly becoming a global pandemic. Driven by this need, here we report for the first time an aptamer-conjugated theranostic magnetic hybrid graphene oxide-based assay for highly sensitive tumor cell detection from blood samples with combined therapy capability. AGE-aptamer-conjugated theranostic magnetic nanoparticle-attached hybrid graphene oxide was developed for highly selective detection of tumor cells from infected blood samples. Experimental data indicate that hybrid graphene can be used as a multicolor luminescence platform for selective imaging of G361 human malignant melanoma cancer cells. The reported results have also shown that indocyanine green (ICG)-bound AGE-aptamer-attached hybrid graphene oxide is capable of combined synergistic photothermal and photodynamic treatment of cancer. Targeted combined therapeutic treatment using 785 nm near-infrared (NIR) light indicates that the multimodal therapeutic treatment is highly effective for malignant melanoma cancer therapy. The reported data show that this aptamer-conjugated theranostic graphene oxide-based assay has exciting potential for improving cancer diagnosis and treatment.