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A methodology previously developed in our laboratory utilized an aliphatic hydrocarbon terminated by thiol groups to tether two redox proteins, i.e., the [4Fe–4S] cluster FB of photosystem I (PS I) and the distal [4Fe–4S] cluster of a [FeFe]-hydrogenase, to create a biohybrid dihydrogen-generating complex. These studies guided the design of a modified 2[4Fe–4S] cluster ferredoxin from Clostridium pasteurianum (CpFd) containing two externally facing cysteine residues in close proximity to each [4Fe–4S] cluster that replaces the aliphatic hydrocarbon dithiol tether. The advantage of using a protein is the potential to create a coupled dihydrogen-generating system in vivo. The wild-type CpFdWT and variants CpFdS11C/D40C, CpFdP20C/P49C, CpFdD7S/D36S, CpFdS11C/D40C/D7S/D36S and CpFdP20C/P49C/D7S/D36S were expressed in Escherichia coli and found to contain ~ 8 Fe and ~ 8 S atoms. The absorption spectra of the wild-type and CpFd variants displayed a peak centered at ~ 390 nm characteristic of a S → Fe charge transfer band that diminishes upon reduction with Na-dithionite. Low-temperature X-band EPR studies of the Na-dithionite-reduced wild-type and CpFd variants showed a complex spectrum indicative of two magnetically coupled [4Fe–4S]1+ clusters. EPR-monitored redox titrations of CpFdWT, CpFdD7S/D36S, CpFdS11C/D40C, CpFdP20C/P49C, CpFdS11C/D40C/D7S/D36S and CpFdP20C/P49C/D7S/D36S revealed redox potentials of − 412 ± 8 mV, − 395 ± 4 mV, − 408 ± 7 mV, − 426 ± 11 mV, − 384 ± 4 mV and − 423 ± 4 mV, respectively. The in vitro PS I–CpFdS11C/D40C/D7S/D36S–Pt nanoparticle complex was the highest performer, generating dihydrogen at a rate of 3.25 μmol H2 mg Chl−1 h−1 or 278.8 mol H2 mol PS I−1 h−1 under continuous illumination.

Poor bioavailability of the broad spectrum antibiotic ciprofloxacin (CIP) is caused by its narrow absorption window in the stomach. With the aim of prolonging the gastric residence time of CIP, we prepared a ternary nanoparticle complex (nanoplex) of CIP by co-complexation with polyanions (sodium dextran sulfate (DXT)) and an anionic amphiphile (sodium dodecyl sulfate (SDS)). We investigated the effect of the charge ratio of DXT to SDS on the size, zeta potential, CIP payload, and CIP utilization rate of the CIP-DXT-SDS nanoplex and its dissolution characteristics in simulated gastrointestinal fluids. Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry analyses showed that the ternary nanoplex was made up of amorphous CIP-DXT and crystalline CIP-SDS complexes. The size of the CIP-DXT-SDS nanoplex prepared at a > 90% CIP utilization rate was 110–290 nm and it had a zeta potential of −16–39 mV, and CIP payload of 47–62%, depending on the charge ratio. At gastric pH, the CIP-DXT-SDS nanoplex prepared with a DXT:SDS charge ratio lower than 80:20 exhibited prolonged CIP release (60% dissolution after 8 h) compared with native CIP (100% dissolution after 1 h) and a binary CIP-DXT nanoplex (80% dissolution after 5 h), which was attributed to its lower solubility. The sustained release characteristics of the CIP-DXT-SDS nanoplex were comparable to those of existing CIP gastroretentive formulations.

Background: Crossing the blood–brain barrier (BBB) is crucial for drug delivery to the brain and for treatment of brain tumors, such as glioblastoma, the most common of all primary malignant brain tumors. Microbubble (MB) is oscillated and destroyed by controlling ultrasound (US) parameters. This oscillation and destruction of MB can open the BBB transiently, and a drug can be delivered to the brain. Materials and methods: For testing the efficiency of delivery to the brain, we synthesized a US-sensitizing nanoparticle (NP) complex via chemically binding MBs and NPs for the BBB opening, including near-infrared dye-incorporated albumin nanoparticles (NIR-Alb NPs) for fluorescence detection. Results: The human-derived, biocompatible NIR-Alb NPs did not show significant cytotoxicity to 500 μg/mL for 3 days in four human glioma cell lines. In an in vivo animal study, some US parameters were investigated to determine optimal conditions. The optimized US conditions were applied in a U87MG orthotopic mouse model. We found that the fluorescence intensity in the brain was 1.5 times higher than in the control group. Conclusion: Our US-sensitizing NP complex and US technique could become one of the critical technologies for drug delivery to the brain.

Oral delivery of curcumin (CUR) has limited effectiveness due to CUR's poor systemic bioavailability caused by its first-pass metabolism and low solubility. Buccal delivery of CUR nanoparticles can address the poor bioavailability issue by virtue of avoidance of first-pass metabolism and solubility enhancement afforded by CUR nanoparticles. Buccal film delivery of drug nanoparticles, nevertheless, has been limited to low drug payload. Herein, we evaluated the feasibilities of three mucoadhesive polysaccharides, i.e., hydroxypropyl methylcellulose (HPMC), starch, and hydroxypropyl starch as buccal films of amorphous CUR-chitosan nanoplex at high CUR payload. Both HPMC and starch films could accommodate high CUR payload without adverse effects on the films' characteristics. Starch films exhibited far superior CUR release profiles at high CUR payload as the faster disintegration time of starch films lowered the precipitation propensity of the highly supersaturated CUR concentration generated by the nanoplex. Compared to unmodified starch, hydroxypropyl starch films exhibited superior CUR release, with sustained release of nearly 100% of the CUR payload in 4 h. Hydroxypropyl starch films also exhibited good payload uniformity, minimal weight/thickness variations, high folding endurance, and good long-term storage stability. The present results established hydroxypropyl starch as the suitable mucoadhesive polysaccharide for high-payload buccal film applications. Nanyang Technological University Published version This work was funded by the Nanyang Research Programme (NRP SCBE01jr 2017) of Nanyang Technological University, Singapore.

A covalent organic framework (COF) is a promising type of porous material with customizable surface characteristics. Confining multiple catalytic units within a mesoporous COF can generate abundant active sites and improve the catalytic performance. In this work, a COF with both metalloporphyrin and a metal nanoparticle complex denoted as hemin/TAPB-DMTP-COF/AuNPs (TAPB: 1,3,5-tris(4-amino-phenyl)benzene, DMTP: 2,5-dimethoxyterephaldehyde, AuNPs: Au nanoparticles) has been successfully fabricated through a hierarchical encapsulation method. The as-synthesized composite was then employed to construct an electrochemical sensing platform for the efficient detection of bisphenol A (BPA). Under the optimal conditions, the hemin/TAPB-DMTP-COF/AuNP sensor presented a linear range of 0.01-3 μmol L-1 and a low detection limit of 3.5 nmol L-1. The satisfactory signal amplification is based on a triple-signaling amplification strategy due to the abundant Fe3+ sites of Fe-porphyrin, high conductivity of AuNPs and a large specific surface area of the TAPB-DMTP-COF. The proposed method was used to measure the content of BPA in different water samples with a satisfactory recovery from 95.5 to 104.0%, suggesting the great potential of the sensor in practical applications.

As a novel developed delivery method for treatment of lung infections, dry powder Inhaler (DPI) delivery attracts more and more attention in studies about inhalation therapy. Conventional dry powder inhaler delivery form is used for administration of nanoparticles (liposomes, polymeric nanoparticles, etc.). However, DPI form for these nanoparticles possesses some drawbacks such as lower payload, lack of long term storage stability. The emergence of nanoparticle complex (nanoplex) is able to improve this situation greatly considering its many merits like higher payload, better long term storage stability, better supersaturation generation ability and so on. Thus here we studied the feasibility of application of nanoplex in DPI form for inhalation therapy of lung infections. Firstly we investigated the effects of dextran chain length on characteristics of ciprofloxacin nanoplex. Characterization of nanoplex showed that chain length can only affect payload and yield of nanoplex in which longer dextran chain resulted in lower payload and higher yield. Afterwards we compared effects of different drying methods (spray drying and spray freeze drying) on aerosolization efficiency of ciprofloxacin nanoplex DPI form powders and effects of different adjuvants in mitigating adverse effects of drying process on supersaturation generation ability of ciprofloxacin nanoplex spray dried powders. In these studies, Carr’s Index, Fine Particle Fraction and other aerodynamic properties were tested and compared in 15 determining whether dried powders possessed capability to deliver nanoplex into infection sites in pulmonary system via inhalation. Supersaturation profiles and dissolution rates were determined to evaluate whether dried powders were able to generate supersaturated drug solution upon reaching the pulmonary system. Data proved the superiority of spray freeze dried powders of ciprofloxacin nanoplex in terms of aerosolization efficiency and importance of hydroxypropyl methylcellulose (HPMC) as adjuvant in maintaining higher level of supersaturated drug solution within longer time period. In this thesis, we also investigated feasibility in developing dual drug nanoplex by using ciprofloxacin and itraconazole as drug models. It was reported that a combination therapy with two antibiotics was able to effectively eradicate Pseudomonas aeruginosa [1] and this inspired us with the idea about developing dual drug nanoplex system. The potential of dual drug nanoplex system in inhalation therapy is promising especially when multi-drug application is needed. The dosage, administration frequency and patient’s compliance will be greatly improved. In this study, different preparation conditions such as acetic acid concentration and mass ratio of drugs were studied for condition optimization of dual drug nanoplex formulation. We can manipulate proportion of payload for each individual drug in dual drug nanoplex by simply changing the mass ratio of drugs during preparation process. 16 In the end, we studied the curcumin (CUR) nanoplex in DPI form and feasibility of curcumin nanoplex formation by complexation with bovine serum albumin (BSA). Curcumin solubility was improved in DPI form regardless of slower dissolution rate resulted from drying process. The superiority of curcumin nanoplex with BSA was proved in this thesis. As a type of protein, BSA has higher bioavailability and be able to render nanoplex better colloidal stability. Denaturation of BSA could affect nanoplex structure which resulted in influences on drug release. CUR-BSA nanoplex had superiority in terms of size, colloidal stability as well as supersaturation generation ability. More BSA in nanoplex meant higher susceptibility of CUR-BSA nanoplex to heat treatment which led to increase in release of curcumin from nanoplex Doctor of Philosophy (SCBE)

This research work aimed at synthesizing and investigating the antimicrobial activities of a metallic oxide nanoparticle complex of Moringa oleifera leaves extracts against some microorganisms. Moringa oleifera leaves were washed, dried and blended. They were extracted with distilled water and ethanol using standard methods. The nanoparticle was synthesized by coordinating with manganese oxide. The physicochemical properties were determined following standard procedures. The phytochemical screening was carried out by standard methods. The antibacterial activities were done using agar well diffusion method. Antifungal activity was carried out following the plate technique. The leaves extract had a 75% yield and melting point of 116 °C while the nanoparticle had a yield of 60% and melted at 78 °C with pH of 3.46. The molar conductance of the nanoparticle revealed at 10.6 Ω−1cm2mol−1. The ethanolic extract of the leaves showed the presence of alkaloids, tannin, steroids and saponins. The ethanolic extract of M. oleifera exhibited the highest antibacterial activity of 33.05±0.10 mm against Bacillus subtilis while its antifungal activity revealed the highest inhibition of 48.40±0.53 mm at 30 mg/mL against Aspergillus niger. Staphylococcus aureus had a zone of inhibition of 19.00±0.16a using the aqueous extract. The ethanolic extract of M. oleifera nanoparticles showed antibacterial and antifungal activity against B. megaterium and A. niger with a zone of inhibition of 49.21±0.32 mm and 50.35±0.29 mm respectively while the aqueous extract showed antibacterial activity against S. aureus with a zone of 26.00±0.38mm. As it was concluded ethanolic extract in both leaves extract and its nanoparticle, possessed higher antibacterial and antifungal activities than the aqueous extract.

Resveratrol (RES) is a natural non-flavonoid polyphenol with cardioprotective activities, antioxidant, antiplatelet, and antiinflammatory. However, its low aqueous solubility, chemical stability, and oral bioavailability, as well as a short circulation half-life greatly limit its clinical applications. To overcome these limitations of RES, we synthesized a methoxy poly(ethylene glycol)-b-oligomerization(D, L-Leucine) (mPEG-b-O(D, L-Leu)) nanoparticle (NP) as the carrier of RES and evaluated the myocardial-protective effectiveness of this RES/NP complex in rat myocardial ischemia-reperfusion injury models. We gauged the characterization of the NP through proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscope, and Fourier transform infrared spectroscopy and then loaded RES on the nanocarrier by hydrophobic interactions under physiological pH to extend the release time of RES and prolong its circulation half-life. Subsequently, we used rat cardiomyocytes (H9C2 cells) and rat MI/RI model to investigate the relationship between drug composition and myocardial preservation properties. It was found that RES was encapsulated quickly and efficiently, and displayed an effectual loading-capacity and in vitro sustained-release. Anti-MI/RI effect of the RES/NP complex was found satisfactory in rat models in vivo using free RES as the control. This study suggested that NP may prove to be a potent nanocarrier to augment the pharmacotherapy of RES against MI/RI.

This study aimed to compare the in vivo effectiveness between curcumin–oligochitosan nanoplexes (CUR–OCH nanoplexes) and oligochitosan-coated curcumin-encapsulated liposomes (OCH-Lip-CUR) w...

Many obstacles restrict development of DNA plasmid-based therapeutic delivery, involving but not limited to poor cellular uptake, premature material dissociation, and inefficient response. Additionally, lack of precision loading of the plasmids on the carrier nanoparticle may affect the overall nonspecificity in terms of loading as well as the site of loading. Here we report a strategy using the incorporation of a biotin-modified nucleotide into a 4.7 kb plasmid sequence for the site-specific nanoparticle conjugation as an improvement on targeted DNA plasmid delivery. Initially, a designed 80-nucleotide sequence was elongated by incorporating biotin-16-aminoallyl-2'-dCTP that facilitated streptavidin binding as determined via polyacrylamide gel electrophoresis (PAGE). This modified sequence was ligated into a specific location of the EGFP plasmid to avoid possible interference with important functional elements and gene expression off of the plasmid. In parallel, a gold nanoparticle complex comprising of either a CD44 or mutant DNA conjugated aptamer, a PEGylated streptavidin, and a derivatized hyaluronic acid stabilizing polymer was synthesized. To delineate the ability of this nanoparticle-plasmid complex to exhibit an improved cellular delivery, MDA-MB-231 cells were treated with a set of plasmid and plasmid-nanoparticle complexes. Successful expression of EGFP was only observed in cells treated with the biotin-modified EGFP plasmid and a streptavidin-CD44 aptamer-nanoparticle. This demonstrated the need for the specific biotin-streptavidin binding to avoid nanoparticle-plasmid dissociation for improved efficacy. This proof-of-principle concept creates a flexible scaffold that can be assimilated into any plasmid and can produce small RNAs or encoding a therapeutic gene via an installation of a design that uses incorporated modified nucleotides as tethering points for nanoparticles which can play host to stabilizing ligands, additional therapeutic molecules and antibody conjugates among other possibilities. In our system, the nanoparticles are vehicles for the addition of targeting ligands that were essential for cell specificity and enhanced cellular uptake.

We present an efficient carbon quantum dots (CQDs)-modified silver nanoparticles (AgNPs) (CQDs-AgNPs) as turn-on fluorescence nanoprobe for monitoring hydrogen sulfide (H2S) in brain microdialysate. The fluorescence of the CQDs-AgNPs probe can be selectively and sensitively turned on by H2S due to the formation of Ag S bonds between AgNPs and H2S and breaking of the Ag N bond between AgNPs and CQDs. Density functional theory (DFT)/time-dependent density functional theory (TD-DFT) investigation were thoroughly conducted on the electronic structures, absorption and emission spectra of CQDs-AgNPs complex as well as the sensing mechanism for hydrogen sulfide. The CQDs-AgNPs fluorescent probe illustrates a wide linear detection range towards H2S from 1 to 1900 nM with the detection limit of ∼0.4 nM. This improved sensitivity, lower limit, along with the high selectivity and fast response toward H2S, makes this CQDs-AgNPs complex successfully monitor H2S basal level in rats without exogenous stimulation, which was calculated to be 3.08 ± 0.10 μM (n = 3). This novel fluorescence probe provides an assay for direct detection of H2S in the cerebral systems and contributes to understand the physiological function and molecular mechanisms of endogenous H2S.

Recently the use of nanomaterials for the diagnosis and detection of malignant diseases has increased due to the versatility and properties of these nanostructures. For this work 60 nm commercial gold nanoparticles (TED PELLA inc.) and Nanostars manufactured by chemical synthesis (precursor reagent: HAuCl4, cationic surfactant: CTAB) of 117 nm were used for coating. Malachite green Isotyocianate (MGITC), mPEG-SH and ortho-pyridyldisulfide-polyethylene glycol-N-succinimidyl propionate (OPSS-PEG-NHS) was used. A SERS active nanoparticle complex was obtained by addition of a solution of MGITC to the gold nanoparticles colloidal solution in a 1:6 ratio. Later, an mPEG-SH solution was added to the mix. The nanoparticle-MGITC-mPEG-SH complex stability was revised using a UV-Vis spectrophotometer and a JEOL JEM 1000 transmission electron microscope. The SERS spectra were registered with a Raman Thermoscientific DXR microscopy system. Amplified bands associated with OPSS-PEG-NHS were identified in 389, 622, 859, 929, 1080, 1283, 1360, 1443, 1490 and 1450 cm-1. The results indicate that through this methodology it is possible to identify gold nanomaterials coated with polymer through the Raman technique. In addition, greater amplification is observed with the use of nanostars compared to gold spheres. Finally, these nanomaterials are available for the marking of specific membrane for the study of different types of cancer by the SERS technique.

Chiral recognition of enantiomers is fundamentally important. In this study, a novel strategy for the chiral discrimination of glucose enantiomers was constructed based on the hydrogen peroxide (H2O2)-mediated generation of a carbon dots-gold nanoparticle (C-dots@Au NP) complex independent of surface modification with chiral ligands. H2O2 is essential as a reductant to promote the growth of Au NPs from gold salts. Besides, the modification of C-dots with sulfhydryl groups is necessary for its anchoring on the surface of Au NPs. Therefore, in the presence of H2O2, the C-dots@Au NP complex can be self-generated from a simple mixture containing C-dots and Au salts. It is worth noting that glucose oxidase can selectively catalyze d-glucose but not l-glucose to generate H2O2. In this regard, the chiral recognition process can trigger the formation of the C-dots@Au NP complex. Furthermore, based on the production of reddish Au NPs and the reduction of C-dot fluorescence quenched by Au NPs, the resultant C-dots@Au NP complex enables achieving the chiral discrimination of glucose enantiomers by combining colorimetric and fluorometric assays. Compared with the conventional approaches that use chiral ligands to decorate NPs, the generation of the chiral-responsive C-dots@Au NP complex is much simpler and faster. Upon combination with specific enzymatic reactions that produce a reductive product, the current strategy provides a general approach for the identification of chiral enantiomers.

Amorphous curcumin-chitosan nanoparticle complex (or nanoplex in short) was recently developed as a new solubility enhancement strategy of curcumin (CUR) – a natural herb well known for its vast therapeutic activities. For its subsequent clinical application and commercialization, the present work aimed to address the three remaining research questions pertaining to the CUR nanoplex, i.e. (1) was the nanoplex preparation scalable? (2) could the nanoplex maintain its solubility enhancement capability in the powder form? (3) could the nanoplex resist crystallization, which would jeopardize its solubility enhancement capability, during long-term storage? First, the results showed that gram-scale production of the CUR nanoplex was readily achieved at high CUR utilization rate without significant adverse effects on the physical characteristics. Stable CUR nanoplex with size, zeta potential, and CUR payload of ≈100–300 nm, 18 mV, and 80%, respectively, was produced. The scaled-up production, nevertheless, resulted in lower yield due to lower nanoplex recovery in the purification step. Second, the CUR nanoplex powders, when formulated correctly with drying adjuvants, maintained the solubility enhancement capability of the suspension form, despite their slower dissolution velocity. High apparent solubility at approximately twice of CUR’s thermodynamic solubility was demonstrated for 8 h. Third, the CUR nanoplex powders maintained its amorphous state after twelve-month storage when stored as physical mixture with crystallization-inhibiting agents. In short, the present results successfully established the CUR nanoplex as a practical and effective solubility enhancement strategy of CUR. Accepted version

Polymeric graft polyphosphazene containing 4-aminobenzoic acid diethylaminoethyl ester (DEAAB) as hydrophobic side groups was rationally designed and named PDEP. PDEP can self-assemble into a nanovesicle in water. More importantly, when compared with the amphiphile poly[(methoxy-poly(ethylene glycol))(ethyl p-aminobenzoate)]phosphazene (PEP) copolymer containing benzene rings and the amphiphile poly[(methoxy-poly(ethylene glycol)(N,N-diisopropylethylenediamine)]phosphazene (PDP) copolymer containing tertiary amino groups, the coexistence of benzene and tertiary amino groups in PDEP enabled it to effectively load water-soluble small-molecule doxorubicin hydrochloride (DOX·HCl) into the vesicle and efficiently induce in situ transformation of gold tetrachloroaurate (HAuCl4) to gold nanoparticles (AuNPs) as both a reductant and a stabilizer. By optimizing the reduction conditions, such as the temperature, reaction time, and hydrophobic group in polymer/HAuCl4 molar ratio, the AuNP complex PDEP vesicles signi...

The use of cancer-relevant microRNA molecules as endogenous drug release stimuli is promising for personalized cancer treatment yet remains a great challenge because of their low abundance. Herein, we report a new type of microRNA-catalyzed drug release system based on DNA-programmed gold nanoparticle (GNP)-quantum dot (QD) complex. We show that a trace amount of miRNA-21 molecules could specifically catalyze the disassembly of doxorubicin (Dox)-loaded GNP-QDs complex through entropy driven process, during which the Dox-intercalating sites are destructed for drug release. This catalytic reaction could proceed both in fixed cells and live cells with miRNA-21 overexpression. Dox molecules could be efficiently released in the cells and translocate to cell nuclei. QD photoluminescence is simultaneously activated during catalytic disassembly process, thus providing a reliable feedback for microRNA-triggered drug release. The GNP-QDs-Dox complex exhibits much higher drug potency than free Dox molecules, and therefore represents a promising platform for accurate and effective cancer cell treatment.

Multifunctional nanoparticles for biomedical applications have shown extraordinary potential as contrast agents in various bioimaging modalities, near-IR photothermal therapy, and for light-triggered therapeutic release processes. Over the past several years, numerous studies have been performed to synthesize and enhance MRI contrast with nanoparticles. However, understanding the MRI enhancement mechanism in a multishell nanoparticle geometry, and controlling its properties, remains a challenge. To systematically examine MRI enhancement in a nanoparticle geometry, we have synthesized MRI-active Au nanomatryoshkas. These are Au core–silica layer–Au shell nanoparticles, where Gd(III) ions are encapsulated within the silica layer between the inner core and outer Au layer of the nanoparticle (Gd-NM). This multifunctional nanoparticle retains its strong near-IR Fano-resonant optical absorption properties essential for photothermal or other near-IR light-triggered therapy, while simultaneously providing increased T1 contrast in MR imaging by concentrating Gd(III) within the nanoparticle. Measurements of Gd-NM revealed a strongly enhanced T1 relaxivity (r1 ∼ 24 mM−1⋅s−1) even at 4.7 T, substantially surpassing conventional Gd(III) chelating agents (r1 ∼ 3 mM−1⋅s−1 at 4.7 T) currently in clinical use. By varying the thickness of the outer gold layer of the nanoparticle, we show that the observed relaxivities are consistent with Solomon–Bloembergen–Morgan (SBM) theory, which takes into account the longer-range interactions between the encapsulated Gd(III) and the protons of the H2O molecules outside the nanoparticle. This nanoparticle complex and its MRI T1-enhancing properties open the door for future studies on quantitative tracking of therapeutic nanoparticles in vivo, an essential step for optimizing light-induced, nanoparticle-based therapies.

The physics models of plasmonics for single nanoparticle, complex single nanoparticle, nanodimer, and single nanoparticle over a metallic thin film with an isolation layer, have been reviewed in this article. In nanoscale, the localized plasmonics from the single nanoparticle, hybrid single nanoparticle, and nanodimer, can be illustrated by classical electrodynamics. When the space of a nanodimer downs to subnanometer, the classical electrodynamics would fail to predict the resonance spectrum or dispersion of the nanostructures. The quantum model and quantum-corrected electrodynamics model, are introduced to deal with this problem. For the single nanoparticle over a metallic thin film with an isolation layer, the plasmonic resonance and the enhanced local field depend on the thickness of the isolation layer strongly. When the isolation layer thickness goes down to subnanometer, the classical electromagnetics model would be replaced by the quantum model for illustrating of the plasmonics. The physics models of plasmonics have wide applications in design and fabrication of the metallic nanostructure for further research.

The objective of this research was to develop new technology for possible noncontact, nondestructive, and culture-independent rapid detection of Salmonella using ferromagnetic nanoparticles. Light signal changes of particles, cells, and their reaction stages were investigated. Amino-functionalized ferromagnetic nanoparticles (amino-FMNs) were synthesized and modified by glutaraldehyde to crosslink the attachment of specific antibodies to the particles. The nanoparticle complex was used to capture, concentrate, and isolate Salmonella in a culture broth. Signal changes of the four stages of the nanoparticles-amino-glutaraldehyde-antibodies-Salmonella cell attachments were tracked with sensitive Synchrotron FTIR spectroscopy (SR-FTIR). The unique peaks from these four steps were identified. Results can be applied to develop a new test method or a new test/universal reader for rapid, nondestructive, and culture-independent detection of Salmonella in food products using IR spectroscopy at wave numbers 1454 cm-1, 1542 cm-1, and 1414 cm-1, respectively.

It is of significant importance to develop an injectable self-healing hydrogel system that can simultaneously deal with antibacterial treatment, tumor therapy and wound healing acceleration for biomedical fields. Herein, a system of CuS nanoparticle complex (CuS NC) hydrogels with multiple functions is firstly developed through incorporating polyethylene glycol (PEG)-functionalized CuS nanoparticles (CuS NPs) with surface amino groups into a 3D network of oxidized dextran (ODex) and PEG with amino end groups. The in situ formed CuS NC hydrogels display not only excellent self-healing and injectable abilities, but also good biocompatibility for biomedical application. The introduction of CuS NPs endows the hydrogels with outstanding photothermal/photodynamic performance under near-infrared laser irradiation, creating the capability to fully kill S.aureus and E.coli bacteria, and to inhibit tumor growth in a subcutaneous skin-tumor model. The CuS NC hydrogels maintain sustained release of Cu2+ and moist microenvironment, and thus effectively accelerate wound healing in vivo. This work illustrates a facile strategy to prepare injectable, multifunctional nanoparticle hybrid hydrogels which can be used severally or simultaneously for bacterial infection treating, skin wound healing and skin-tumor therapy.

Molecular modeling of a supramolecular catalytic system is conducted resulting from the assembling between a small peptide and the surface of cationic self-assembled monolayers on gold nanoparticles, through a multiscale iterative approach including atomistic force field development, flexible docking with Brownian Dynamics and µs-long Molecular Dynamics simulations. Self-assembly is a prerequisite for the catalysis, since the catalytic peptides do not display any activity in the absence of the gold nanocluster. Atomistic simulations reveal details of the association dynamics as regulated by defined conformational changes of the peptide due to peptide length and sequence. Our results show the importance of a rational design of the peptide to enhance the catalytic activity of peptide–nanoparticle conjugates and present a viable computational approach toward the design of enzyme mimics having a complex structure–function relationship, for technological and nanomedical applications.

Neural diseases, like Alzheimer’s (AD) and Parkinson’s (PD) are widely expanding portions of neurodegenerative diseases, are related to norepinephrine (NE) concentration with proportional correlation. However, quantification of NE is quite difficult because NE coexists with ascorbic acid (AA) and uric acid (UA), which interferes with detecting NE in biological fluid. We fabricated a multi-modified electrode with reduced graphene oxide sheets (GS) and gold nanoparticles (GNPs) for highly selective and sensitive detection of NE. Thus, GS-GNPs modified electrode could enhance the sensitivity for detection of NE, as well as highly sensitive manner with AA. Compared with recent studies, our newly developed sensor appears to have not only a wide detection range (0.2-10 μM), but also superior detection limit (200 nM) in presence of 2000 times higher concentration of AA.

A systematic study of the interaction of bovine serum albumin (BSA) with MnO2 nanoparticles (NPs) was carried out. MnO2 nanoparticles were prepared via a low temperature (90 °C) single-step precipitation route in the absence of surfactant/template and characterized using XRD, TEM, FESEM, FTIR, XPS, and Raman spectroscopy. MnO2 particles were found to have a length of 900 nm and a diameter of 10 nm. The interaction of BSA with NP was investigated using various spectroscopic and biophysical techniques under physiological pH 7.4. MnO2 effectively quenches the intrinsic fluorescence of BSA through static quenching. The effect of MnO2 on the conformation of BSA was analyzed using circular dichroism (CD), Fourier transform infrared (FTIR), and Raman spectroscopy, and it was observed that the secondary structure of BSA altered after the interaction with MnO2. Thermal CD spectroscopy revealed insignificant variation in the melting temperature of BSA upon binding to MnO2. Additionally, the morphological changes of BSA upon interaction with MnO2 were characterized using a field emission scanning electron microscope (FESEM). Moreover, the increase in the size of the BSA–MnO2 complexes was analyzed using dynamic light scattering (DLS). This study shows that the adsorption of BSA on MnO2 is dependent on the concentration of the protein as well as the NP.

Chirality plays a key role in biochemical reaction and the self-assembled mechanism of life. The detection of chiral molecules is one crucial issue in biology, clinic, pharmacy and food security fields, which usually refers to the detectable chiroptical effect, i.e. circular dichroism (CD) and optical rotatory dispersion (ORD) Gansel et al. (2009), Quake and Scherer (2000), Pendry (2004), Zhang et al. (2009), Kastel et al. (2007) 1-5. However, the chiroptical effect from chiral molecules in nature (such as proteins and DNAs) is usually very small and located in ultraviolet spectral region. This limits the detection sensitivity of chiral molecules and their ability to control electromagnetic wave. In this paper, we report a scalable fabrication of a new kind of chiral molecule@nanoparticle complex materials, which are composed of an achiral nano-cup array and a pair of chiral molecules (l-/d-cysteine). The nano-cup array with localized surface plasmonic response peak of 630nm is obtained with the micro-sphere assembly technique, which is a kind of scalable, low-cost and material-independent fabrication method. After coating a layer of chiral molecules on the surface of the nano-cup array, a clear induced-CD peak in visible region is demonstrated from the l/d-cysteine@nano-cups complex materials, the intensity of which can be much greater than the existing results 9-16. Full-wave electromagnetic simulation method has been performed to get insight into the mechanism of the induced chiroptical effect. The simulation results indicate that this giant induced CD signal should be attributed to the electromagnetic interaction between chiral molecules and plasmonic nanostructures, especially for the wave at the plasmonic resonance peak. These results indicate the potential application prospect of these newly-fabricated complex chiral materials. Display Omitted A new kind of molecule@nanoparticle complex materials are fabricated.The complex materials have greatly enhanced induced CD signal in visible region.The physical mechanism of induced CD signal is studied.

To meet the need for high-throughput immunoassays, many multiplex fluorescent immunoassays have been proposed. Most of them need different kinds of fluorescent label indicators during the test. In this work, a novel indirect ELISA-inspired dual-channel fluorescent immunoassay based on 3-mercaptopropionic acid capped CdTe/ZnS quantum dots (QDs) was constructed. The ELISA wells were coated with two kinds of antigen-QD complex. When the primary antibodies were present in a sample, they mediated the binding of a secondary antibody-DNA-gold nanoparticle complex to the antigen-QD complex. Then the gold nanoparticles quenched the fluorescence of the QDs and a decrease in fluorescence intensity was observed. Thus, the amount of primary antibody could be estimated from the decrease of fluorescence intensity. Owing to the wide absorption range and the relatively narrow emission band of the QDs, the dual-channel fluorescent immunoassay system could work at the same excitation wavelength and the emission wavelengths of each channel had no interference. As a result, two different kinds of primary antibody could be detected at the same time in one ELISA well, which simplified the operation and greatly improved the efficiency. Besides, only one type of secondary antibody needs to be added to the prepared microtiter plates, which further simplified the operation during the detection procedure. This dual-channel fluorescent immunoassay system will provide new insights into high-throughput immunodetection. Graphical abstract.

We report herein the design of a novel biosensing strategy for the detection of carcinoembryonic antigen (CEA), based on the use of Janus-type nanoparticles having Au and silica opposite faces as integrated electrochemical biorecognition-signaling system. The Janus nanoparticles were properly functionalized with horseradish peroxidase on the silica surface to act as signaling element, and a biotin thiol-modified anti-CEA DNA hairpin aptamer the Au face to assemble the biorecognition element. The sensing approach relies on the first specific recognition of CEA by the bifunctionalized Janus nanoparticles, causing unfolding of the DNA hairpin structure and unmasking the biotin residues at the aptamer chain. This CEA-Janus nanoparticle complex was then captured by avidin-modified Fe3O4@SiO2 NanoCaptors®, allowing further magnetic deposition on carbon screen printed electrodes for the amperometric detection of the cancer biomarker. The Janus nanoparticles-based aptasensor was able to detect CEA in the range from 1 to 5000 ng mL−1 (5.5 pM–28 nM) with a detection limit of 210 pg mL−1 (1.2 pM). The aptasensor also showed high reproducibility and storage stability, and was successfully validated in human serum.

In recent years, there is significant growth in the bacterial resistance to various classic antibiotics. This has opened and enhanced the field of metal nanoparticles and antibiotic-metal nanoparticle complex. This research was designed to load a glycopeptide antibiotic named vancomycin on citrate-capped silver nanoparticles to enhance its antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Colloidal solution of silver nanoparticles (AgNPs) was prepared by chemical reduction method using silver nitrate (AgNO3) as a precursor in the presence of ionic surfactant trisodium-citrate which acts as a both capping and reducing agent. Synthesized nanoparticles were functionalized with vancomycin to form nano-drug complex (Van@AgNPs). Various analytical techniques such as UV-vis absorption spectra, FTIR, DLS, TEM and XRD were carried out to study the loading and interaction of drug with silver nanoparticles. The observed shift in SPR peak of UV-vis and various reflections of XRD spectra is attributed towards the loading of vancomycin on silver nanoparticle surface. FTIR studies shows the hydrogen bonding between vancomycin and silver nanoparticles through NH (amine) group of vancomycin and oxygen of anionic citrate. The increase in average particle size and particle size distribution of vancomycin-loaded nanoparticles in comparison to bare NPs also hints the drug loading. Agar well diffusion method was used to study the synergetic antibacterial activity of vancomycin-loaded silver nanoparticles against both test strains. The well diffusion test showed the notable enhancement in antibacterial activity against both class of bacteria. This enhancement has been observed to be synergetic rather than the additive.

While the wound healing activity of curcumin (CUR) has been well-established, its clinical effectiveness remains limited due to the inherently low aqueous CUR solubility, resulting in suboptimal CUR exposure in the wound sites. Previously, we developed high-payload amorphous nanoparticle complex (or nanoplex) of CUR and chitosan (CHI) capable of CUR solubility enhancement by drug-polyelectrolyte complexation. The CUR-CHI nanoplex, however, exhibited poor colloidal stability due to its strong agglomeration tendency. Herein we hypothesized that the colloidal stability could be improved by replacing CHI with its oligomers (OCHI) owed to the better charge distribution in OCHI. The effects of key parameters in drug-polyelectrolyte complexation (i.e. pH, salt inclusion, CUR concentration, and OCHI/CUR charge ratio) on the physical characteristics and preparation efficiency of the CUR-OCHI nanoplex produced were investigated. The in vivo wound healing efficacy of the CUR-OCHI nanoplex and its cytotoxicity towards human keratinocytes cells were examined. The results showed that CUR-OCHI nanoplex exhibited prolonged colloidal stability (72 h versus 90% after 7 days versus 9 days for the native CUR resulting in smaller scars, attributed to its generation of high CUR concentration in the wound sites. Nanyang Technological University Accepted version The authors would like to acknowledge the research funds from Vietnam Atomic Energy Institute and Nuclear Research Institute (Grant number: 07/17/VNCHN) and from Nanyang Technological University's Undergraduate Research Experience on Campus (URECA) for Suen Ern Lee.

The biosynthesis of metal nanoparticle and their suitable assembly has recently gained tremendous interest for its application in biomedical arena such as substrates for surface-enhanced Raman scattering and others. In this article, an easy, low-cost, fast, bio-friendly and toxic-reducing agent free protocol has been described for the preparation of silver nanoparticle film using biocompatible 1,2-dipalmitoyl-sn-glycero-3-phosphocholine phospholipid Langmuir monolayer template. Interactions, docking and attachment of silver ions to the above-mentioned phospholipid monolayer have been studied by surface pressure–area isotherm and compressibility analysis at the air–water interface. We have deposited the Langmuir–Blodgett monolayer/multilayer containing silver nanoparticle onto glass/SiO2/quartz substrates. The formation of phospholipid–silver nanoparticle complex in Langmuir–Blodgett film has been characterized by field emission-scanning electron microscopy and high-resolution tunneling electron microscopy images. We have applied this deposited film as a substrate for surface-enhanced Raman scattering application using rhodamine 123 to understand the existence of the surface plasmon activity of silver nanoparticle.

Objectives: To carry out a proof-of-concept study on the development of dual-drug amorphous nanoparticle complex (nanoplex in short) as a potential formulation platform for fixed-dose combination (FDC) of poorly-soluble drugs. Significance: FDC has been proven effective in improving patient compliance for treatment that requires complex multidrug regimen. Currently, there is growing interest to develop FDC of poorly-soluble drugs due to the increased number of drugs exhibiting poor solubility thus low bioavailability. Methods: The dual-drug nanoplex was prepared by electrostatically-driven co-complexation of drug molecules with oppositely charged dextran sulfate, using ciprofloxacin (CIP) and itraconazole (ITZ) as the model poorly-soluble drugs. Results: We first verified that the co-complexation products were dual-drug CIP-ITZ nanoplex, and not binary mixtures of the single-drug CIP and ITZ nanoplexes, by demonstrating their distinct thermal behaviors and dissolution characteristics. Depending on the preparation condition, the dual-drug nanoplex exhibited size and zeta potential of 160–410 nm and −35–50 mV, respectively. The individual drug payloads were readily manipulated by varying the CIP/ITZ mass ratio in the feed, resulting in CIP and ITZ payloads in the range of 60-30% and 15-45%, respectively. The CIP-ITZ nanoplex, however, exhibited diminished CIP supersaturation generation, thus lower CIP solubility enhancement, compared to the single-drug CIP nanoplex. The CIP-ITZ nanoplex, nonetheless, remained capable of generating high ITZ supersaturation level. Conclusion: Dual-drug nanoplex was successfully prepared with a high degree of control over its physical characteristics. Nevertheless, whether dual-drug nanoplex always exhibits diminished solubility enhancement compared to its single-drug counterparts needs to be investigated using different poorly-soluble drugs. Accepted version The authors would like to acknowledge the funding from GlaxoSmithKline (GSK) Singapore under their Green and Sustainable Manufacturing Trust Fund 2013 (PI: Kunn Hadinoto Ong).

Silver–moxifloxacin (Ag–Mox) and gold–moxifloxacin (Au–Mox) nanoparticles were successfully synthesized by a rapid and convenient method, which exhibited good stability against variations in NaCl solution, pH and temperature. The structural features of these nanoparticles were ascertained by UV-Vis, AFM, FTIR, SEM and EDX techniques while EDX analysis revealed the inorganic composition of the synthesized moxifloxacin-capped Ag and Au NPs. Similarly, the stability of the nanoparticle complex may be attributed to the binding of the amino group to the silver and gold surface, respectively. Silver–moxifloxacin nanoparticles (Ag–Mox) exhibited significant urease enzyme inhibitory activity (0.66 ± 0.042 μg mL−1) even 250 times better compared to moxifloxacin (183.25 ± 2.06 μg mL−1). On the contrary, gold nanoparticles (Au–Mox) remained inactive to the same enzyme. Antibacterial assay was also carried out for the parent compound as well as its noble metal nano-conjugates, which gave encouraging results.

Fei Tong,1,2 Suhuan Liu,1 Bing Yan,1 Xuejun Li,1 Shiwei Ruan,3 Shuyu Yang1 1Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, 2Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang, 3Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Abstract: The purpose of the study was to reveal the therapeutic effect of quercetin (QUE) nanoparticle complex on diabetic nephropathy (DN) by regulating the expression of intercellular adhesion molecular-1 (ICAM-1) on endothelium as compared to free QUE. QUE 10 mg/kg as a single abdominal subcutaneous injection daily for 8 weeks continuously in diabetic rats and 10 mg/kg QUE nanoparticle complex as a single abdominal subcutaneous injection every 5 days, continuously administered for 8 weeks to diabetic rats. Blood and left kidneys were collected; pathological change of kidney, renal function, oxidative stress level, blood glucose level, serum lipid, urine protein, and albumin/creatinine ratio were measured; and neutrophil adhesion, ICAM-1 expression, and CD11b+ cells infiltration were observed. Both QUE and QUE nanoparticle complex preconditioning ameliorated the pathological damage of kidney and improved renal function, alleviated renal oxidative stress injury, restricted inflammatory cells infiltration, and downregulated the ICAM-1 expression as compared to DN group, while QUE nanoparticle complex significantly alleviated this effect. Keywords: nanoparticle complex, quercetin, DN, ICAM-1, CD11b+, endothelium

While the solubility enhancement capability of amorphous drug-polyelectrolyte nanoparticle complex (nanoplex) has been widely established, its amorphous form stability during long-term storage is often lacking for poorly-soluble drugs with high crystallization propensity, such as curcumin (CUR). Herein we presented a new stabilization strategy of amorphous CUR nanoplex using a secondary small-molecule drug – ibuprofen (IBU) – as the auxiliary stabilizer to the polyelectrolytes (i.e. chitosan). The results showed that, unlike the single-drug CUR nanoplex, the dual-drug CUR-IBU nanoplex with CUR/IBU payload ratio of 1.7 remained stable after 24-month storage. The CUR-IBU nanoplex also exhibited superior CUR solubility enhancement (4-fold higher) than the CUR nanoplex. These improvements, however, were not evident for the CUR-IBU nanoplex prepared at higher CUR/IBU payload ratio of 14 due to insufficient IBU presence. Compared to the CUR nanoplex, the CUR-IBU nanoplex exhibited smaller size with less spherical morphology (100 nm), higher zeta potential (42 versus 19 mV), lower total drug payload (73% versus 83%), and lower CUR utilization rate (53% versus 94%) due to the competition with IBU in the drug-PE complexation. These results successfully established the use of a secondary drug to not only stabilized, but also improved solubility enhancement of amorphous drug nanoplex systems.

Specific protein detection by means of antibody-nanoparticle conjugates is a new field in medical nanobiotechnology. Among many nanoparticles used, gold nanoparticles show strong light-absorption properties which have been exploited in designing nanobiosensors. Fibronectin (FN) plays an important role in extracellular matrix (ECM) structure and function of normal cells; however, in conditions like lung carcinoma, its expression increases, especially in non small cell lung carcinoma (NSCLC). In this study, we conjugated gold nanoparticles to human fibronectin antibody (anti-hFN) to design a colorimetric nanobiosensor for detection of FN present in ECM of cultured cells. Three different cell lines, namely A549 (target cells), AGO-1522 (control cells), and Nalm-6 (negative control cells), were used to compare changes in color resulting from aggregation of gold nanoparticles due to higher amount of FN. Our construct was able to detect increased level of FN which was distinguishable visually by change in color and could be confirmed by spectrophotometer as well.

In this study, a novel design of gold nanoparticle (AuNP) probe containing large number of enzymes is reported for ultrasensitive detection of Escherichia coli (E. coli) O157:H7. The AuNP was functionalized with a polyclonal antibody (Pab) that has an affinity for E. coli O157:H7. The digoxigenin (DIG) incorporated oligonucleotides were covalently attached on the AuNP. And then Horseradish peroxidase (HRP) labeled anti-DIG was bound to the DIG incorporated oligonucleotide on the AuNP. Afterwards, magnetic microparticles (MMPs) were functionalized with monoclonal antibody (Mab) to E. coli O157:H7 and used to form a sandwich structure with target E. coli O157:H7 and AuNP probes via immune reaction. A magnetic field was used to effectively remove unbound AuNP probes. Finally, we exploited the reaction of HRP enzyme immobilized on AuNP probes with tetramethylbenzidine (TMB) that is a substrate of HRP, followed by stopping the reaction with 2 M H2SO4. The resulting end products were analyzed by UV-vis spectroscopy. Using this method, we could detect ca. 102 CFU/ mL of E. coli O157:H7 within an hour.

Amorphous drug-polyelectrolyte nanoparticle complex (or nanoplex in short) has emerged as a highly attractive solubility enhancement strategy of poorly-soluble drugs attributed to its simple and highly efficient preparation. The existing nanoplex formulation, however, exhibits poor amorphous form stability during long-term storage for drugs with high crystallization propensity. Using ciprofloxacin (CIP) and sodium dextran sulfate (DXT) as the model drug-polyelectrolyte nanoplex, we investigated the feasibility of incorporating crystallization inhibiting agents, i.e. hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), at the nanoplex formation step to improve the physical stability of the CIP nanoplex. The effects of the HPMC or PVP additions on the nanoplex's physical characteristics (i.e. size, zeta potential, CIP payload), CIP utilization rate, dissolution rate, and supersaturation generation were also examined. The results showed that the additions of HPMC or PVP increased the CIP nanoplex size (from 300 to 500 nm) and CIP utilization rate (from 65% to 90% w/w) with minimal impacts on the CIP payload (70–80% w/w). Their additions had opposite impacts on the nanoplex's colloidal stability due to surfactant nature of PVP. Significantly, unlike the CIP-DXT and CIP-DXT-PVP nanoplexes, the CIP-DXT-HPMC nanoplex remained amorphous after three-month accelerated storage, while also exhibited superior solubility enhancement (15–30% higher).

Multifunction nanoparticle complexes have previously been developed to aid physicians in both diagnosis and treatment of cancerous tissue. Here, we designed a nanoparticle complex structure that consists of a plasmonically active hollow gold nanoshell core surrounded by photoluminescent quantum nanocrystals (QNs) in the form of PbS encapsulated by a silica layer. There are three main design variables including HGN synthesis and optical tuning, formation of the silica layer on the hollow gold nanoshell surface, and fabrication and photoluminescence tuning of PbS quantum nanocrystals. The hollow gold nanoshells were deliberately designed to function in the optical regimes that maximize tissue transmissivity (800 nm) and minimize tissue absorption (1100 nm). Secondly, several chemical ligands were tested such as (3-mercaptopropyl)trimethoxysilane and mercaptoundecanoic acid for controlled growth of the silica layer. Last, PbS QNs were synthesized and optimized with various capping agents, where the nanocrystals excited at the same wavelength were used to activate the photothermal properties of the hollow gold nanoshells. Upon irradiation of the complex with a lower power 800 nm laser, the nanocrystals luminesce at 1100 nm. At ablative temperatures the intrinsic luminescent properties of the QNs are altered and the luminescent output is significantly reduced (>70%). While this paper focuses on synthesis and optimization of the QN–HGN complex, in the future we believe that this novel particle complex design may have the potential to serve as a triple theranostic agent, which will aid satellite tumor localization, photothermal treatment, and ablative confirmation.

Nanoparticle-based platforms for gene therapy and drug delivery are gaining popularity for cancer treatment. To improve therapeutic selectivity, one important strategy is to remotely trigger the release of a therapeutic cargo from a specially designed gene- or drug-laden near-infrared (NIR) absorbing gold nanoparticle complex with NIR light. While there have been multiple demonstrations of NIR nanoparticle-based release platforms, our understanding of how light-triggered release works in such complexes is still limited. Here, we investigate the specific mechanisms of DNA release from plasmonic nanoparticle complexes using continuous wave (CW) and femtosecond pulsed lasers. We find that the characteristics of nanoparticle-based DNA release vary profoundly from the same nanoparticle complex, depending on the type of laser excitation. CW laser illumination drives the photothermal release of dehybridized single-stranded DNA, while pulsed-laser excitation results in double-stranded DNA release by cleavage of the Au-S bond, with negligible local heating. This dramatic difference in DNA release from the same DNA-nanoparticle complex has very important implications in the development of NIR-triggered gene or drug delivery nanocomplexes.

Objective: To investigate the effects of varying molecular weight (MW) of chitosan (CHI) used in the complexation with curcumin (CUR) on the physical and dissolution characteristics of the amorphous CUR–CHI nanoparticle complex produced. Significance: Amorphous CUR–CHI nanoparticle complex (or CUR nanoplex in short) recently emerged as a promising bioavailability enhancement strategy of CUR attributed to its fast dissolution, supersaturation generation capability, and simple preparation. Existing CUR nanoplex prepared using low MW CHI, however, exhibited poor colloidal stability during storage. Herein we hypothesized that the colloidal stability could be improved by using CHI of higher MW. The effects of this approach on the nanoplex’s other characteristics were simultaneously investigated. Methods: The CUR nanoplex was prepared by electrostatically driven self-assembled complexation between CUR and oppositely charged CHI of three different MWs (i.e. low, medium, and high). Besides colloidal stability, the effects of MW variation were investigated for the nanoplex’s (1) other physical characteristics (i.e. size, zeta potential, CUR payload, amorphous state stability), (2) preparation efficiency (i.e. CUR utilization rate, yield), and (3) dissolutions under sink condition and supersaturation generation. Results: CUR nanoplex prepared using CHI of high MW exhibited improved colloidal stability, larger size, superior morphology, and prolonged supersaturation generation. On the other hand, the effects of MW variation on the payload, amorphous state stability, preparation efficiency, and dissolution under sink condition were found to be insignificant. Conclusions: Varying MW of CHI used was an effective means to improve certain aspects of the CUR nanoplex characteristics with minimal adverse effects on the others.