25 research outputs found
Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H2N-PEG-NH2). Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study
The Sabatier principle for Battery Anodes: Chemical Kinetics and Reversible Electrodeposition at Heterointerfaces
How surface chemistry influences reactions occurring thereupon has been a
long-standing question of broad scientific and technological interest for
centuries. Recently, it has re-emerged as a critical question in a
subdiscipline of chemistry - electrochemistry at heterointerphases, where the
answers have implications for both how, and in what forms, humanity stores the
rising quantities of renewable electric power generated from solar and wind
installations world-wide. Here we consider the relation between the surface
chemistry at such interphases and the reversibility of electrochemical
transformations at a rechargeable battery electrode. Conventional wisdom holds
that stronger chemical interaction between the metal deposits and electrode
promotes reversibility. We report instead that a moderate strength of chemical
interaction between the deposit and the substrate, neither too weak nor too
strong, enables highest reversibility and stability of the plating/stripping
redox processes at a battery anode. Analogous to the empirical Sabatier
principle for chemical heterogeneous catalysis, our finding arises from the
confluence of competing processes - one driven by electrochemistry and the
other by chemical alloying. Based on experimental evaluation of metal
plating/stripping systems in battery anodes of contemporary interest, we show
that such knowledge provides a powerful tool for designing key materials in
highly reversible electrochemical energy storage technologies based on
earth-abundant, low-cost metals.Comment: 64 pages. Initially submitted on March 16th, 2021; revised version
submitted on November 14th, 2021 to the same Journa
Functional lanthanide-based nanoprobes for biomedical imaging applications
Lanthanide-doped upconversion nanoparticles (UCNPs) are perceived as promising
novel near-infrared (NIR) bioimaging agents characterised by high contrast and high
penetration depth. However, the interactions between charged UCNPs and
mammalian cells have not been thoroughly studied and the corresponding
intracellular uptake pathways remain unclear.
Herein, my research work involved the use of hydrothermal method and ligand
exchange approach to prepare UCNP-PVP, UCNP-PEI, and UCNP-PAA. These
polymer-coated UCNPs demonstrated good water dispersibility, the similar size
distribution as well as similar upconversion luminescence efficiency. However, the
positively charged UCNP-PEI evinced greatly enhanced cellular uptake in
comparison with its neutral or negative counterparts, as revealed by cellular uptake
studies. Meanwhile, it was discovered that cationic UCNP-PEI could be effectively
internalized mainly through the clathrin endocytic machanism. This study is the first
report on the endocytic mechanism of positively charged lanthanide-doped UCNPs.
Furthermore, it allows us to control the UCNP-cell interactions by tuning surface
properties.
Glioblastoma multiforme (GBM) is the most common and malignant form of primary
brain tumors in humans. Small molecule MRI contrast agents are used for GBM
diagnosis and preoperative tumor margin delineation. However, the conventional
gadolinium-based contrast agents have several disadvantages, such as a relatively low
T1 relaxivity, short circulation half lives and the absence of tumor targeting efficiency.
Multimodality imaging probes provide a better solution to clearly delineate the
localization of glioblastoma.
My research work also involved the development of multimodal nanoprobes for
targeted glioblastoma imaging. Two targeted paramagnetic/fluorescence nanoprobes
were designed and synthesized, UCNP-Gd-RGD and AuNP-Dy680-Gd-RGD.
UCNP-Gd-RGD was prepared through PEGylation, Gd3+DOTA conjugation and
RGD labeling of PEI-coated UCNP-based nanoprobe core (UCNP-NH2). It adopted
the cubic NaYF4 phase, had an average size of 36 nm by TEM, and possessed a
relatively intense upconversion luminescence of Er3+ and Tm3+. It also exhibited
improved colloidal stability and reduced cytotoxicity compared with UCNP-NH2, and
a higher T1 relaxivity than Gd3+DOTA. AuNP-Dy680-Gd-RGD was synthesized
through bioconjugation of amine-modified AuNP-based nanoprobe core (AuNPPEG-
NH2) by a NIR dye (Dy680), Gd3+DOTA and RGD peptide. It demonstrated a
size of 3–6 nm by TEM, relatively strong NIR fluorescence centered at 708 nm, longterm
physiological stability, and an enhanced T1 relaxivity compared with
Gd3+DOTA.
Targeting abilities of both UCNP-Gd-RGD and AuNP-Dy680-Gd-RGD towards
overexpressed integrin αvβ3 receptors on U87MG cell surface was confirmed by their
enhanced cellular uptake visualized by confocal microscopy imaging and quantified
by ICP-MS, where their corresponding control nanoprobes were used for comparison.
Furthermore, targeted imaging capabilities of UCNP-Gd-RGD and AuNP-Dy680-Gd-
RGD towards subcutaneous U87MG tumors were verified by in vivo and ex vivo
upconversion fluorescence imaging studies and by in vivo and ex vivo NIR
fluorescence imaging and in vivo MR imaging studies, respectively. These two
synthesized targeted nanoprobes, with surface-bounded cyclic RGD peptide and
numerous T1 contrast enhancing molecules, are applicable in targeted MR imaging
glioblastoma and delineating the tumor boundary. In addition, UCNP-Gd-RGD
favors the upconversion luminescence with NIR-to-visible nature, while AuNPDy680-
Gd-RGD possesses NIR-to-NIR fluorescence, and both lead to their potential
applications in fluorescence-guided surgical resection of gliomas.published_or_final_versionChemistryDoctoralDoctor of Philosoph
Facial Feature Extraction Using Frequency Map Series in PCNN
Pulse coupled neural network (PCNN) has been widely used in image processing. The 3D binary map series (BMS) generated by PCNN effectively describes image feature information such as edges and regional distribution, so BMS can be treated as the basis of extracting 1D oscillation time series (OTS) for an image. However, the traditional methods using BMS did not consider the correlation of the binary sequence in BMS and the space structure for every map. By further processing for BMS, a novel facial feature extraction method is proposed. Firstly, consider the correlation among maps in BMS; a method is put forward to transform BMS into frequency map series (FMS), and the method lessens the influence of noncontinuous feature regions in binary images on OTS-BMS. Then, by computing the 2D entropy for every map in FMS, the 3D FMS is transformed into 1D OTS (OTS-FMS), which has good geometry invariance for the facial image, and contains the space structure information of the image. Finally, by analyzing the OTS-FMS, the standard Euclidean distance is used to measure the distances for OTS-FMS. Experimental results verify the effectiveness of OTS-FMS in facial recognition, and it shows better recognition performance than other feature extraction methods
Inflammation Targeted Gd<sup>3+</sup>-Based MRI Contrast Agents Imaging Tumor and Rheumatoid Arthritis Models
Inflammatory responses are closely
related to cancer progression
and several diseases. Anti-inflammatory drugs that bind to inducible
enzymes can be used as biomarkers for molecular imaging. Selective
targeted contrast agents are expected to improve contrast-to-noise
ratio (CNR) in MRI at the site of inflammation. In this work, three
new Gd<sup>3+</sup> DO3A-amide MRI contrast agents (CAs) that conjugated
to mefenamic acid (MA), a commonly used nonsteroidal anti-inflammatory
drug (NSAID), through different linkers, ethylenediamine (GdL1), 2,2′-oxidiethylamine
(GdL2) and 4,7,10-trioxa-1,13-tridecanediamine (GdL3) were studied.
Their relaxivities were GdL1 (4.74 mM<sup>–1</sup> s<sup>–1</sup>), GdL2 (4.77 mM<sup>–1</sup> s<sup>–1</sup>), and
GdL3 (4.95 mM<sup>–1</sup> s<sup>–1</sup>) at 400 MHz
at 25 °C. Their serum albumin binding properties were studied
by tryptophan emission-quenching experiments, with GdL1 showing a
preferential binding toward HSA and BSA as compared with GdL2 and
GdL3. They showed low cytotoxicities toward HeLa cells at high concentration
(0.5 mM) and high cellular uptake in U87 cells as compared with GdDOTA. <i>In vivo</i> MRI showed increased T1-weighted contrast after
intravenous injection of the agents. Moreover, T1 contrast was significantly
enhanced for 1.5 h in the U87 tumor model and 2 h in the arthritis
joint in adjuvant-induced arthritis (AIA) model at dosages of 0.1
and 0.03 mmol/kg, respectively. Most of the agents were cleared at
24 h post-administration in the AIA model with no observable T1 contrast.
GdL1–3 showed superior retentions and intensity enhancements
(IEs) at the kidney, liver, tumor, and arthritis joint to those of
GdDOTA. GdL3 showed the highest relaxivity and IE at the arthritis
joint and is therefore a potential candidate to be developed as MRI
CAs that target inflammation
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Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel.
How metazoan mechanotransduction channels sense mechanical stimuli is not well understood. The NOMPC channel in the transient receptor potential (TRP) family, a mechanotransduction channel for Drosophila touch sensation and hearing, contains 29 Ankyrin repeats (ARs) that associate with microtubules. These ARs have been postulated to act as a tether that conveys force to the channel. Here, we report that these N-terminal ARs form a cytoplasmic domain essential for NOMPC mechanogating in vitro, mechanosensitivity of touch receptor neurons in vivo, and touch-induced behaviors of Drosophila larvae. Duplicating the ARs elongates the filaments that tether NOMPC to microtubules in mechanosensory neurons. Moreover, microtubule association is required for NOMPC mechanogating. Importantly, transferring the NOMPC ARs to mechanoinsensitive voltage-gated potassium channels confers mechanosensitivity to the chimeric channels. These experiments strongly support a tether mechanism of mechanogating for the NOMPC channel, providing insights into the basis of mechanosensitivity of mechanotransduction channels
Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel.
How metazoan mechanotransduction channels sense mechanical stimuli is not well understood. The NOMPC channel in the transient receptor potential (TRP) family, a mechanotransduction channel for Drosophila touch sensation and hearing, contains 29 Ankyrin repeats (ARs) that associate with microtubules. These ARs have been postulated to act as a tether that conveys force to the channel. Here, we report that these N-terminal ARs form a cytoplasmic domain essential for NOMPC mechanogating in vitro, mechanosensitivity of touch receptor neurons in vivo, and touch-induced behaviors of Drosophila larvae. Duplicating the ARs elongates the filaments that tether NOMPC to microtubules in mechanosensory neurons. Moreover, microtubule association is required for NOMPC mechanogating. Importantly, transferring the NOMPC ARs to mechanoinsensitive voltage-gated potassium channels confers mechanosensitivity to the chimeric channels. These experiments strongly support a tether mechanism of mechanogating for the NOMPC channel, providing insights into the basis of mechanosensitivity of mechanotransduction channels