Chi-An Cheng - Academia.edu (original) (raw)

Papers by Chi-An Cheng

medRxiv (Cold Spring Harbor Laboratory), Jan 11, 2022

The emergence of the SARS-CoV-2 Omicron variant has motivated a re-evaluation of the test charact... more The emergence of the SARS-CoV-2 Omicron variant has motivated a re-evaluation of the test characteristics for lateral flow immunochromatographic assays (LFIAs), commonly referred to as rapid antigen tests. To address this need, we evaluated the analytic sensitivity of one of the most widely used LFIAs in the US market, the Abbott BinaxNOW™ COVID-19 Ag At-Home Card using 32 samples of Omicron and 30 samples of the Delta variant. Samples were chosen to intentionally over-represent the range of viral loads where differences are most likely to appear. We found no changes in the analytic sensitivity of the BinaxNOW™ assay by variant even after controlling for variation in cycle threshold values in the two populations. Similar to prior studies, the sensitivity of the assay is highly dependent on the amount of virus present in the sample. While the analytic sensitivity of the BinaxNOW™ LFIA remains intact versus the Omicron variant, its clinical sensitivity is influenced by the interaction between viral replication, the dynamics of tissue tropism and the timing of sampling. Further research is necessary to optimally adapt current testing strategies to robustly detect early infection by the Omicron variant to prevent transmission. .

Nanotheranostics, 2019

Rationale: Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in th... more Rationale: Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. In this setting, real-time monitoring of therapy and tumor site would give the clinicians a handle to observe therapeutic response and to quantify drug amount to optimize the treatment. In this work, we developed a liposome-based cargo (cancer drugs) delivery strategy that could simultaneously monitor the real-time alternating magnetic field-induced cargo release from the change in MRI relaxation parameter R 1 and the location and condition of liposome from the change in R 2. The tumor site can then be monitored during the cargo release because liposomes would passively target the tumor site through the enhanced permeability and retention (EPR) effect. Physical insights from the experimental results and corresponding Monte Carlo spin dynamics simulations were also discussed. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles, diethylenetriaminepentaacetic acid gadolinium(III) (Gd(III)-DTPA), and a model cancer drug (fluorescein) were co-loaded in PEGylated thermosensitive liposomes. The liposomes were characterized by transmission electron cryo-microscopy (cryoTEM), dynamic light scattering (DLS), and inductively coupled plasma optical emission spectrometry (ICP-OES). Alternating magnetic field (AMF) was used to create controlled mild hyperthermia (39-42°C) and facilitate controlled cargo (fluorescein) release from the thermosensitive liposomes. MRI relaxation parameters, R 1 and R 2 , were measured at room temperature. The temporal variation in R 1 was used to obtain the temporal profile of cargo release. Due to their similar sizes, both the gadolinium and cargo (model cancer drug fluorescein) would come out of the liposomes together as a result of heating. The temporal variation in R 2 was used to monitor SPIO nanoparticles to enhance the tumor contrast. Monte Carlo spin dynamics simulations were performed by solving the Bloch equations and modeling SPIO nanoparticles as magnetized impenetrable spheres. Results: TEM images and DLS measurements showed the diameter of the liposome nanoparticle ~ 200 nm. AMF heating showed effective release of the model drug. It was found that R 1 increased linearly by about 70% and then saturated as the cargo release process was completed, while R 2 remained approximately constant with an initial 7%-drop and then recovered. The linear increase in R 1 is consistent with the expected linear cargo release with time upon AMF heating. Monte Carlo spin dynamics simulations suggest that the initial temporal fluctuation of R 2 is due to the plausible changes of SPIO aggregation and the slow non-recoverable degradation of liposomal membrane that increases water permeability with time by the heating process. The simulations show an order of magnitude increase in R 2 at higher water permeability. Conclusion: We have performed MR parameter study of the release of a cargo (model cancer drug, fluorescein) by magnetic heating from thermosensitive multifunctional liposomes loaded with dual contrast agents. The size of the liposome nanoparticles loaded with model cancer drug (fluorescein), gadolinium chelate, and SPIO nanoparticles was appropriate for a variety of cancer therapies. A careful and detailed analysis with theoretical explanation and simulation was carried out to investigate the correlation between MRI relaxation parameters, R 1 and R 2 , and different cargo release fractions. We have quantified the cargo release using R 1 , which shows a linear relation between each other. This result provides a strong basis for the dosage control of drug delivered. On the other hand, the fairly stable R 2 with almost constant value suggests that it could be used to monitor the position and condition of the liposomal site, as SPIO nanoparticles mostly remained in the aqueous core of the liposome. Because our synthesized SPIO-encapsulated liposomes could be targeted to tumor site passively by the EPR effect, or actively through magnetofection, this study provides a solid ground for developing MR cancer theranostics in combination of this nanostructure and AMF heating strategy. Furthermore, our simulation results predict a sharp increase in R 2 during the AMF heating, which opens up the exciting possibility of high-resolution, high-contrast real-time imaging of the liposomal site during the drug release process, provided AMF heating could be incorporated into an MRI setup. Our use of the clinically approved materials, along with confirmation by theoretical simulations, make this technique a promising candidate for translational MR cancer theranostics.

RSC Advances, 2023

Although nanotechnologies have attractive attributes in cancer therapy, their full potential has ... more Although nanotechnologies have attractive attributes in cancer therapy, their full potential has yet to be realized due to challenges in their translation to clinical settings. The evaluation of cancer nanomedicine

Frontiers in Immunology, Oct 26, 2022

Background: Immunocompromised (IC) patients show diminished immune response to COVID-19 mRNA vacc... more Background: Immunocompromised (IC) patients show diminished immune response to COVID-19 mRNA vaccines (Co-mV). To date, there is no 'empirical' evidence to link the perturbation of translation, a rate-limiting step for mRNA vaccine efficiency (VE), to the dampened response of Co-mV. Materials and methods: Impact of immunosuppressants (ISs), tacrolimus (T), mycophenolate (M), rapamycin/sirolimus (S), and their combinations on Pfizer Co-mV translation were determined by the Spike (Sp) protein expression following Co-mV transfection in HEK293 cells. In vivo impact of ISs on SARS-CoV-2 spike specific antigen (SpAg) and associated antibody levels (IgG Sp) in serum were assessed in Balb/c mice after two doses (2D) of the Pfizer vaccine. Spike Ag and IgG Sp levels were assessed in 259 IC patients and 50 healthy controls (HC) who received 2D of Pfizer or Moderna Co-mV as well as in 67 immunosuppressed solid organ transplant (SOT) patients and 843 nontransplanted (NT) subjects following three doses (3D) of Co-mV. Higher Co-mV concentrations and transient drug holidays were evaluated. Results: We observed significantly lower IgG SP response in IC patients (p<0.0001) compared to their matched controls in 2D and 3D Co-mV groups. IC patients on M or S showed a profound dampening of IgG SP response relative to those that were not on these drugs. M and S, when used individually or in combination, significantly attenuated the Co-mV-induced Sp expression, whereas T did not exert significant influence. Sirolimus combo Frontiers in Immunology frontiersin.org 01

Chemical Communications, 2020

Proceedings of the National Academy of Sciences of the United States of America, Oct 13, 1998

Inorganic chemistry frontiers, 2023

Pb2+-doped Cs2Mn(Cl/Br)4·2H2O PA NCs exhibit excellent luminescence properties and stability, and... more Pb2+-doped Cs2Mn(Cl/Br)4·2H2O PA NCs exhibit excellent luminescence properties and stability, and can be used in fibers and other uses.

ACS Applied Materials & Interfaces, Aug 30, 2018

The use of nanocarriers to deliver poorly soluble drugs to the sites of diseases is an attractive... more The use of nanocarriers to deliver poorly soluble drugs to the sites of diseases is an attractive and general method, and mesoporous silica nanoparticles (MSNs) are increasingly being used as carriers. However, both loading a large amount of drugs into the pores and still being able to release the drug is a challenge. In this paper we demonstrate a general strategy based on a companion molecule that chaperones the drug into the pores and also aids it in escaping. A common related strategy is to use a miscible co-solvent DMSO, but although loading may be efficient in DMSO, this co-solvent frequently diffuses into an aqueous environment leaving the drug behind. We demonstrate the method by using acetophenone (AP), an FDA approved food additive as the chaperone for clofazimine (CFZ), a water-insoluble antibiotic used to treat leprosy and multidrug-resistant tuberculosis. AP enables high amount of CFZ cargo into the MSNs and also carries CFZ cargo out from the MSNs effectively when they are in an aqueous bio-relevant environment. The amount of loading and the CFZ release efficiency from MSNs were optimized; 4.5 times more CFZ was loaded in MSNs with AP than that with DMSO and 2300 times more CFZ was released than that without the assistance of the AP. In vitro treatment of macrophages infected by Mycobacterium tuberculosis with the optimized CFZ-loaded MSNs killed the bacteria in the cells in a dose-dependent manner. These studies demonstrate a highly efficient method for loading nanoparticles with water-insoluble drug molecules and the efficacy of the nanoparticles in delivering drug into eukaryotic cells in aqueous media.

ACS Nano, Jan 18, 2019

Non-invasive stimuli-responsive drug delivery using magnetic fields in conjunction with superpara... more Non-invasive stimuli-responsive drug delivery using magnetic fields in conjunction with superparamagnetic nanoparticles offers the potential of spatial and temporal control of drug release. When hyperthermia is not desired and control of the dosage is required, it is necessary to design a platform in which local heating on the nanoscale releases the therapeutic cargo without bulk heating of the surrounding medium. In this paper we report a design using a stimuli

Tissue is translucent to shortwave infrared (SWIR) light, rendering optical imaging superior in t... more Tissue is translucent to shortwave infrared (SWIR) light, rendering optical imaging superior in this region. However, the widespread use of optical SWIR imaging has been limited, in part, by the lack of bright, biocompatible contrast agents that absorb and emit light above 1000 nm. J-aggregation offers a means to transform stable, near-infrared (NIR) fluorophores into redshifted SWIR contrast agents. Here we demonstrate that hollow mesoporous silica nanoparticles (HMSNs) can template the J-aggregation of NIR fluorophore IR-140 to result in nanomaterials that absorb and emit SWIR light. The J-aggregates inside PEGylated HMSNs are stable for multiple weeks in buffer and enable high resolution imaging in vivo with 980 nm excitation.

Carbon nanostructures, 2016

Diamond nanoparticle hosting negatively-charged nitrogen vacancy (NV−) center has unique chemical... more Diamond nanoparticle hosting negatively-charged nitrogen vacancy (NV−) center has unique chemical, optical and spin properties in a wide range of nanotechnology applications. For instance, diamond nanoparticles containing NV centers have been well-known as Fluorescent NanoDiamond (FND) for fluorescence imaging. Recently the NV− center has been applied for nanothermometry. In this chapter we are going to discuss the recent advances of the NV− center for bioimaging and quantum sensing.

Heliyon, Dec 1, 2022

Ba 2 La 2.85-x (SiO 4) 3 F:0.15Tb 3+ ,xSm 3+ phosphors were prepared for the first time. Energy t... more Ba 2 La 2.85-x (SiO 4) 3 F:0.15Tb 3+ ,xSm 3+ phosphors were prepared for the first time. Energy transfer mechanism from Tb 3+ to Sm 3+ is quadrupole-quadrupole interaction.

RSC Advances, 2022

The polychromatic phosphor with an apatite structure Ca 2 La 3 (SiO 4) 3 F:0.15Tb 3+ ,xSm 3+ (CLS... more The polychromatic phosphor with an apatite structure Ca 2 La 3 (SiO 4) 3 F:0.15Tb 3+ ,xSm 3+ (CLSOF:0.15Tb 3+ ,xSm 3+) was synthesized via a solid-state route. The phase and morphology of the phosphor has been investigated by means of X-ray diffraction (XRD) and scanning electron microscopy (SEM). The structures of the as-prepared phosphor were verified by means of the Rietveld method. The optical performance was investigated thoroughly and the phosphors could emit multicolor light from short wavelengths to long wavelengths by gradually increasing the doping contents of samarium. All the results support that the energy transfer in CLSOF:0.15Tb 3+ ,xSm 3+ contributes to the color tunable property of the phosphor. to generate red light when used as a phosphor activator, whereas terbium has the potential to emit green light when used as a phosphor sensitizer. 11-13 An apatite compound is oen selected to serve as the host because of its changeable crystal eld environment and its strong chemical stability, which is unaffected by the former. M 10 (XO 4) 6 Y 2 is the chemical formula for the apatite structural compound and M might serve as a monovalent cationusually an alkali metalbut also a trivalent cation like a lanthanide element, or even a divalent cation like an alkaline earth metal; X denotes S, Ge, Si, and P, among others; Y is most commonly shorthand for the element halogen and the element oxygen, both of which function as channel anions. 14-16 Compounds of apatite have been the subject of much research in a variety of elds and for several different usages. For instance, Sr 9-Gd(PO 4) 5 (SiO 4)F 2 , 17 Ba 2 La 3 (SiO 4) 3 F, 18 Ba 2 La 3 (SiO 4) 3 Cl, 19 etc. Considering that several single-phase multicolor phosphors may be generated via the transfer of energy between rare earth ions, structure regulation allows for the production of many variations that may be generated from the crystal structure of apatite, which has the potential to remarkably increase the variety of luminous materials and give other alternatives for the sector of solid-state lighting. However, as far as we are aware, there have been no reports concerning Ca 2 La 3 (SiO 4) 3 F (CLSOF) doped with samarium and terbium as of yet. We generated the Tb 3+ /Sm 3+ doped with Ca 2 La 3 (SiO 4) 3 F phosphor that features an apatite structure so that we could examine its structure as well as its luminescence characteristics, particularly the energy transmission. Adjustable phosphors in the colors green, yellow, orange, and red were produced by progressively modifying the doping ratio of rare earth ions. The host material remained unchanged during this process.

RSC Advances, 2021

As promising low-dimensional semiconductor materials, cesium lead halide (CsPbX 3 , X ¼ Cl, Br, I... more As promising low-dimensional semiconductor materials, cesium lead halide (CsPbX 3 , X ¼ Cl, Br, I) perovskite-like nanowires (NWs) can be widely applied to the field of semiconductor devices and integrated optoelectronics. Therefore, developing a facile and efficient synthesis method of cesium lead halide perovskite-like NWs can bring both fundamental and practical impacts to the field of optoelectronics. Here, we developed a synthesis strategy of all-inorganic cesium lead halide CsPbI 3 perovskite-like NWs under catalyst-free, solution-phase, and low-temperature conditions. The synthesis strategy was designed such that no inert gas is required and thus enables the synthesis to be carried out in air, which significantly reduces temperature, steps, time, and cost required for the reaction. The assynthesized NWs were 7 mm in length and 80-100 nm in diameter with ideal morphology. Most of the CsPbI 3 NWs were crystallized in orthorhombic phases that were arranged orderly with a uniform growth direction. In addition, the CsPbI 3 NWs showed a photoluminescence peak near 610 nm and the fluorescence lifetime was 7.34 ns. The photoluminescence mechanism of CsPbI 3 NWs involves the selftrapping behaviour in the radiative recombination process. The composition of CsPbI 3 NWs is highly related to the synthesis temperature. The facile synthesis strategy has opened up a novel path for the synthesis of perovskite-like NWs, laying the foundation for the application of nano-optoelectronic devices, fluorescent anti-counterfeiting, and fluorescent composite materials.

Nanoscale, 2021

We report the design, synthesis and function of core@shell nanoparticles that are responsive to p... more We report the design, synthesis and function of core@shell nanoparticles that are responsive to purely physical stimuli and that have two unusual and disparate properties: they release size-selected cargo and function as Boolean logic gates.

Transplantation and Cellular Therapy, May 1, 2023

Nature Nanotechnology, Aug 4, 2013

Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repair... more Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45-CD54 1 CD157 1 lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of selfrenewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.

Inorganic Chemistry Frontiers

Circulation

Background: Cases of adolescents and young adults developing myocarditis after vaccination with s... more Background: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. Methods: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children’s Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2–specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2–specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects. Results: Extensive antibody ...