Water-dispersible Nanoparticles Research Articles

Water-dispersible and Biocompatible Polymer-based Organic Upconversion Nanoparticles for Transdermal Delivery

Water-dispersible and Biocompatible Polymer-based Organic Upconversion Nanoparticles for Transdermal Delivery

Hyaluronic acid-coated iron oxide nanoparticles for magnetic fluid hyperthermia and methylene blue dye removal: Preparation, physicochemical characterization, and enhancing the heating efficiency

We report here the magnetic fluid hyperthermia properties of water-dispersible hyaluronic acid-coated superparamagnetic iron oxide nanoparticles (HA-MNPs), prepared using the coprecipitation technique followed by ligand exchange. The presence of the hyaluronic acid coating is confirmed using Fourier transform infrared spectroscopy. Magneto-calorimetric studies show good field-induced heating efficiency of the HA-MNPs, where a high specific absorption rate (SAR) of ∼ 315 W/gFe is obtained for ∼ 5 wt% MNP concentration when exposed to an alternating magnetic field amplitude of ∼ 33.1 kA/m at ∼ 126 kHz. The heating efficiency is found to decrease by ∼ 33.8 % after immobilization of the MNPs within an agar matrix, which is attributed to the abrogation of Brownian relaxation. When subjected to an external DC magnetic field, the MNPs form linear chain-like structures, which causes the effective anisotropy energy density to increase. Magneto-calorimetric studies on agar-based oriented samples reveal a ∼ 19.5 % enhancement in SAR, thereby partly compensating for the loss in heating efficiency due to an increase in medium viscosity. The orientational ordering-induced enhancement in SAR is also verified using sweeping rate modified Stoner-Wohlfarth model-based calculations. In vitro cyto-toxicity studies on the HeLa cell lines reveal good cyto-compatibility of the MNPs. The negative charge on the surface of HA-coated MNPs is exploited to remove the cationic methylene blue dye from the aqueous medium, where the dye molecules are found to be physisorbed on the surface of the MNPs. The experimental findings clearly show the high induction heating efficiency, cyto-compatibility, and cationic dye-adsorption efficiency of the prepared HA-MNPs, thereby indicating the suitability of these MNPs for multi-functional applications like magnetic fluid hyperthermia and waste-water purification.

T7 Peptide-modified macrophage membrane-coated nanoplatform for enhanced glioma treatment

The efficient and secure delivery of intravenous chemotherapeutic agents across the blood–brain barrier (BBB) to the precise location of a brain tumor is a crucial element in glioma treatment. Herein, we introduce a biomimetic nanoplatform (T7-M-C/S) comprising a core made up of irinotecan hydrochloride (CPT11) and its bioactive metabolite, 7-Ethyl-10-hydroxycamptothecin (SN38), surrounded by a layer of T7-peptide-modified macrophage membrane. CPT11 spontaneously assembles with SN38 into stable and water-dispersible nanoparticles (C/S), greatly enhancing the water solubility of SN38. The integration of the modified peptide with the inherent proteins expressed by macrophage cells confers the nanoplatform with enhanced bioavailability and robust glioma-targeting abilities, ultimately resulting in superior therapeutic outcomes. These discoveries highlight a drug delivery system characterized by a high drug loading capacity, leveraging the macrophage membrane, and promising significant potential for glioma treatment.

Enhancing Root Canal Therapy with NIR-II Semiconducting Polymer AIEgen and Low-Concentration Sodium Hypochlorite Synergy.

Despite significant efforts to eliminate bacterial biofilm within root canals, achieving effective disinfection remains challenging due to the complex anatomy and limitations of disinfectants. In this study, a second near-infrared (NIR-II) semiconducting polymer with aggregation-induced emission (AIE) properties, named PIDT-TBT, is deliberately designed and synthesized. This proposes an AIE luminogen-based sterilization strategy in synergy with a low concentration of sodium hypochlorite (NaClO). Water-dispersible PIDT-TBT nanoparticles (NPs) are prepared, demonstrating good biocompatibility, as well as photothermal and photodynamic properties. Subsequent antibacterial tests show that PIDT-TBT NPs exhibit excellent bactericidal effects against three bacterial strains: Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis, upon 808nm laser irradiation. In synergy with a low concentration of NaClO (0.5%) solution, PIDT-TBT NPs significantly improves the outcome of root canal treatment under 808nm laser irradiation in a human extracted tooth root canal infection model. Additionally, it is found that PIDT-TBT NPs combine with a low concentration of NaClO solution could safely dissolve dentin debris and further increase the efficiency of root canal preparation by altering the elemental composition of the inner root canal wall.

Antibacterial rice protein nanoparticles with a high curcumin loading for fruit preservation

Curcumin (Cur) exhibits potential as a food preservative because of its natural antibacterial and antioxidant properties. Nevertheless, its practical application is challenging due to poor water solubility and physicochemical instability. In this study, we prepared Cur-loaded protein nanoparticles (RCs) with a high loading capacity. The water-dispersible nanoparticles (10–30 nm) enclosing Cur with a loading capacity of up to 302 mg/g protein were formed by neutralizing rice proteins (RPs) from alkali-unfolded RPs utilizing cation exchange resin in the presence of Cur. Compared to free Cur, RCs improved the heat-stability and photo-stability of Cur by 26.7% and 23.2%, respectively. The RCs demonstrated significantly higher antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) compared to free Cur, with inhibition rates exceeding 94.45% and 91.00%, respectively. Additionally, RCs exhibited superior antioxidant activities across multiple assays, with RCs5 showing increases of 122.22% (DPPH), 64.99% (ABTS), and 94.72% (FRAP) compared to free curcumin. RCs significantly preserved freshly-cut apples, with the RCs5 group showing the lowest bacterial count (1.46 log CFU/g) and the highest total soluble solid content (10.45%) after 7 days of storage. RCs also reduced weight loss to 34.35% of the control and effectively minimized browning by at least 5.83% compared to the control group. These findings highlight the potential use of RCs to improve the antimicrobial and antioxidant activities of encapsulated phytochemicals, which may have numerous applications in, for example, food preservations.

BF2-Bridged Azafulvene Dimer-Based 1064 nm Laser-Driven Superior Photothermal Agent for Deep-Seated Tumor Therapy.

Small organic photothermal agents (PTAs) with absorption bands located in the second near-infrared (NIR-II, 1000-1700 nm) window are highly desirable for effectively combating deep-seated tumors. However, the rarely reported NIR-II absorbing PTAs still suffer from a low molar extinction coefficient (MEC, ϵ), inadequate chemostability and photostability, as well as the high light power density required during the therapeutic process. Herein, we developed a series of boron difluoride bridged azafulvene dimer acceptor-integrated small organic PTAs. The B-N coordination bonds in the π-conjugated azafulvene dimer backbone endow it the strong electron-withdrawing ability, facilitating the vigorous donor-acceptor-donor (D-A-D) structure PTAs with NIR-II absorption. Notably, the PTA namely OTTBF shows high MEC (7.21×104 M-1 cm-1), ultrahigh chemo- and photo-stability. After encapsulated into water-dispersible nanoparticles, OTTBF NPs can achieve remarkable photothermal conversion effect under 1064 nm irradiation with a light density as low as 0.7 W cm-2, which is the lowest reported NIR-II light power used in PTT process as we know. Furthermore, OTTBF NPs have been successfully applied for in vitro and in vivo deep-seated cancer treatments under 1064 nm laser. This study provides an insight into the future exploration of versatile D-A-D structured NIR-II absorption organic PTAs for biomedical applications.

Modulated upconversion luminescence of water-dispersed NaErF4@NaYF4 nanoparticles by introducing Tm3+/Ho3+ as energy capture centers under multi-wavelength NIR excitation

Water-dispersed red upconversion nanoparticles (UCNPs) have great application prospects in the biomedical field. Thus, a series of Er3+-based upconversion nanoparticles (Er-UCNPs) with excellent red upconversion luminescence under three-wavelength NIR excitation (808/980/1550 nm) were prepared by a simple thermal decomposition method, and then further functionalized by PAA to achieve good water dispersibility. Compared with NaErF4 bare core, the emission intensity of Er-UCNPs samples doping of 0.5%Tm3+ and 0.5%Ho3+ as energy capture centers was significantly enhanced, and further improved after coating with NaYF4 inert shell. Meanwhile, among all Er-UCNPs@NaYF4 samples, NaErF4@NaYF4 exhibited the highest emission intensity and longest luminescence lifetime due to the efficient suppression of luminescence quenching effect, while NaErF4:0.5%Tm3+@NaYF4 showed highest red luminescence purity owing to the energy transfer process between Tm3+(3H5) and Er3+(4I13/2). The hydrophilic Er-UCNPs@NaYF4@PAA samples still maintained good red luminescence under multi-wavelength excitation. The luminescence enhancement mechanism in Er-UCNPs@NaYF4 was discussed in detail based on spectral characteristics. The as-prepared water-dispersed Er-UCNPs@NaYF4@PAA with bright red luminescence under multi-wavelength NIR excitation will have potential applications in targeted therapy and deep tissue imaging.

Dual Roles of the Photooxidation of Organic Amines for Enhanced Triplet-Triplet Annihilation Upconversion in Nanoparticles.

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

Full color control and patterned display device from cyan/magenta/yellow water-dispersed electrochromic polymer nanoparticles systems

Electrochromic polymers (ECPs) have great application potential in flexible displays, and there is an increasing expectation of using green methods to form ECP films. Herein, we propose a modified microemulsion method to prepare cyan/magenta/yellow (C/M/Y) water-dispersed electrochromic polymer nanoparticles (WDEN) systems. Three polymer films (WDECP-C/M/Y) maintain similar electrochemical properties compared to their corresponding organic solvent-based polymer films. It is intriguing that WDECP-C/M/Y exhibit better electrochromic properties in terms of higher cycling stability (97.24%, 95.05%, and 52.84%, respectively) and faster switching time (0.94 s, 1.09 s, and 1.34 s for coloring time, respectively) due to the introduction of nanoparticles. In addition, it can achieve various desired colors by blending the C/M/Y WDEN systems in different ratios. The calculated chromaticity coordinates of the blending polymer films show close values to the experimental observation, and the calculated ΔE * ab values range from 2.6 to 10.3, which may provide theoretical guidance for precisely color control. Finally, large-scale and patterned devices were assembled, which can achieve colored-to-colorless reversible electrochromism at a low driving voltage of 0–1.5 V. This work puts forward a universal and environmentally sustainable strategy to prepare WDEN systems, demonstrating their wide range of applications in display devices and electronic tags.

Visible-light-excited robust room-temperature phosphorescence of dimeric single-component luminophores in the amorphous state

Organic room temperature phosphorescence (RTP) has significant potential in various applications of information storage, anti-counterfeiting, and bio-imaging. However, achieving robust organic RTP emission of the single-component system is challenging to overcome the restriction of the crystalline state or other rigid environments with cautious treatment. Herein, we report a single-component system with robust persistent RTP emission in various aggregated forms, such as crystal, fine powder, and even amorphous states. Our experimental data reveal that the vigorous RTP emissions rely on their tight dimers based on strong and large-overlap π-π interactions between polycyclic aromatic hydrocarbon (PAH) groups. The dimer structure can offer not only excitons in low energy levels for visible-light excited red long-lived RTP but also suppression of the nonradiative decays even in an amorphous state for good resistance of RTP to heat (up to 70 °C) or water. Furthermore, we demonstrate the water-dispersible nanoparticle with persistent RTP over 600 nm and a lifetime of 0.22 s for visible-light excited cellular and in-vivo imaging, prepared through the common microemulsion approach without overcaution for nanocrystal formation.

The Molecular Footprint of Peptides on the Surface of Ultrasmall Gold Nanoparticles (2 nm) Is Governed by Steric Demand.

Ultrasmall gold nanoparticles were functionalized with peptides of two to seven amino acids that contained one cysteine molecule as anchor via a thiol-gold bond and a number of alanine residues as nonbinding amino acid. The cysteine was located either in the center of the molecule or at the end (C-terminus). For comparison, gold nanoparticles were also functionalized with cysteine alone. The particles were characterized by UV spectroscopy, differential centrifugal sedimentation (DCS), high-resolution transmission electron microscopy (HRTEM), and small-angle X-ray scattering (SAXS). This confirmed the uniform metal core (2 nm diameter). The hydrodynamic diameter was probed by 1H-DOSY NMR spectroscopy and showed an increase in thickness of the hydrated peptide layer with increasing peptide size (up to 1.4 nm for heptapeptides; 0.20 nm per amino acid in the peptide). 1H NMR spectroscopy of water-dispersed nanoparticles showed the integrity of the peptides and the effect of the metal core on the peptide. Notably, the NMR signals were very broad near the metal surface and became increasingly narrow in a distance. In particular, the methyl groups of alanine can be used as probe for the resolution of the NMR spectra. The number of peptide ligands on each nanoparticle was determined using quantitative 1H NMR spectroscopy. It decreased with increasing peptide length from about 100 for a dipeptide to about 12 for a heptapeptide, resulting in an increase of the molecular footprint from about 0.1 to 1.1 nm2.

Fluorescent molecular systems based on carborane-perylenediimide conjugates.

This study presents the successful synthesis of two perylenediimide (PDI)-based ortho-carborane (o-carborane) derivatives, PDI-CB1 and PDI-CB2, through the insertion of decaborane into alkyne-terminated PDIs (PDI1 and PDI2). The introduction of o-carborane groups did not alter the optical properties of the PDI units in solution compared to their carborane-free counterparts, maintaining excellent fluorescence quantum yields of around 100% in various solvents. This was achieved by using a methylene linker to minimize electronic interaction between PDI and o-carborane, and by incorporating bulky o-carborane groups at imide- position to enhance solubility and prevent π-π stacking-induced aggregation. Aggregation studies demonstrated that PDI-CB1 and PDI-CB2 have greater solubility than PDI1 and PDI2 in both nonpolar and aqueous solvents. Despite the steric hindrance imparted by the o-carborane units, the solid state emission of PDI-CB1 and PDI-CB2 was affected by aggregation-caused fluorescence quenching. However, solid PDI-CB1 preserved bright red excimer-type emission, which persisted in water-dispersible nanoparticles, indicating potential for application as a theranostic agent combining fluorescence bioimaging with anticancer boron neutron capture therapy (BNCT) due to its high boron content.

Synthesis of amphiphilic cationic polyesters and their antibacterial activity

Water-dispersible, biodegradable and green-emitting polyester nanoparticles with cationic aromatic pendants have been prepared and the structural parameters influencing their broad-spectrum antibacterial properties have been examined.

Water Dispersible Colloidal Metal and Metal Oxide Nanoparticles Synthesis for Agarwood Inoculation: A Review

Agarwood is one of the most expensive natural products, produced from Aquilaria Spp. These plants produce agar resin through mechanical, biological, or chemical stress. Besides these, the particles having size in the range of 1-100 nm, are known as nanoparticles, have ultra-high surface area and surface plasmon resonance, can create stress on living plants when incorporated into the plant body. Adopting this concept, we intend to produce agarwood by inoculating water-dispersible metal/metal oxide nanoparticles. Therefore, we aim to synthesize water-dispersible four noble metals (Au, Ag, Pt, Pd) and five metal oxides (Fe3O4, TiO2, SnO2, MnO2, CuO) nanoparticles in aqueous colloidal states for application in biotechnology, considering the facile synthetic routes, readily available and inexpensive precursors, and stability of the products under normal laboratory conditions for an extended period, utilizing the synthesis methods of precipitation of metal/metal oxide nanoparticles from an aqueous solution, microwave and ultrasound-assisted rapid heating methods, sol-gel methods, and surfactant-assisted microemulsion methods. We believe that by applying any of these methods, water-dispersible, long-lasting colloidal metal/metal oxide nanoparticles can be synthesized using a simple laboratory setup, without the need for sophisticated tools or instruments. IUBAT Review, 6(2): 41-76

The influence of the polyol solvents on the continuous growth of water-dispersible iron oxide nanoparticles

Magnetic nanoparticles have continued to gain significant attention due to their unique magnetic properties and potential applications. However, it is still challenging to directly synthesize water-dispersible magnetic nanoparticles with controlled size for biomedical applications. This study investigates the influence of solvents on the continuous growth of magnetic nanoparticles, aiming to achieve controlled size and excellent water dispersibility via thermal decomposition in polyol solvents. The size of the nanoparticles gradually increases with longer polyol chain solvents. The increase in nanoparticles size is more significant under a higher reaction temperature (220 °C) compared to a lower temperature (190 °C). These monodispersed nanoparticles exhibit strong superparamagnetic properties, improving with longer solvent chain lengths at the same size. Magnetic resonance imaging (MRI) studies reveal higher relaxivities for magnetic nanoparticles synthesized in longer-chain polyols. This research offers valuable insights for synthesizing magnetic nanoparticles with precise sizes, magnetic properties, and biomedical applications.Graphical abstract

Carbon nano-onions: Individualization and enhanced water dispersibility

Carbon nano-onions (CNOs) are a unique class of carbon nanomaterials, with a concentric fullerene-like structure and sp2-hybridized carbon atoms. Onions present high mechanical strength, good conductivity, the capability to intercalate alkali metals, showing promising applications in diverse fields, such as tribology, energy storage, and nanomedicine. Their production has been developed by several techniques, with the most interesting being the thermal annealing of carbon nanodiamonds because of the easy scalability (gram-scale) and morphologic control (size and shape form perfectly spherical to polygonal). However, this synthesis is commonly affected by the formation of strong aggregates larger than 100 nm, attributed to carbon soot formation or strong van der Waals interactions, hindering the work with small and individual particles, leading to an altered yield of functionalization. In this study we propose a method for CNO individualization based on strong acid treatment, yielding highly water dispersible nanoparticles. Analytical ultracentrifugation (AUC) analysis is employed as a technique to investigate the particle dimensions directly in dispersion, permitting an ensemble analysis free from further sample preparation bias. Moreover, we also provide a comprehensive evaluation of the common post-synthetic treatment methods, and their effects. By means of scanning transmission electron microscopy with medium angle annular dark field detector and electron energy loss spectroscopy (STEM-MAADF and EELS) we have shown images of individual CNOs. Their successful separation achieved in this study is significant for future research and applications in nanomedicine, electrochemistry, and materials composites, where sample homogeneity is critical.

A design strategy of pure Type-I thiadiazolo[3,4-g]quinoxaline-based photosensitizers for photodynamic therapy

Most photosensitizers (PSs) for photodynamic therapy (PDT) can generate singlet oxygen through transferring energy with oxygen, called Type-II PSs. However, the microenvironment of solid tumor is usually anoxic. Type-I PSs can generate reactive oxygen species (ROS) through transferring electron to substrate, showing more efficient in PDT. But pure Type-I PSs are very rare. The relationship between PSs’ chemical structure and Type-I mechanism has not been explicitly stated. In this study, two thiadiazolo [3,4-g]quinoxaline (TQ) PSs (PsCBz-1 and PsCBz-2) are synthesized through introducing carbazole groups to the 4,9-position of TQ backbone. Comparing with their prototype PS, 4,9-dibrominated TQ (TQs-4), the introduction of carbazole groups reverses the reaction mechanism of PSs from pure Type-II to pure Type-I. Excitingly, the water-dispersible nanoparticles (NPs) of PsCBz-1 can achieve strong phototoxicity in vitro under both normoxia and hypoxia through Type-I mechanism. In addition, PsCBz-1 NPs also exhibits remarkable PDT antitumor effect in vivo. This study provides a feasible design strategy for pure Type-I PSs.

Laser-Synthesized Elemental Boron Nanoparticles for Efficient Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 µg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a 10B concentration of 40 µg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of α-particles.

Acceptor engineering of semiconducting oligomers for improved NIR-II fluorescence imaging and therapy

Fluorescence imaging (FI) conducted over second near-infrared (NIR-II) window shows superior performance with deeper penetration, higher temporal and spatial resolution than that over the first near-infrared (NIR-I) window. Various attempts have been made to develop ideal fluorophores with high brightness, longer emission wavelength and good biocompatibility for NIR-II FI. Here, we design and synthesize three D-A-D type oligomers through acceptor engineering approach to compare their optical properties. The newly prepared oligomer (O3) based on thiadiazolobenzotriazole (TBZ) acceptor exhibits the highest NIR-II brightness compared with the counterparts because of the weakest intramolecular charge transfer transition. Water-dispersed O3 nanoparticles (NPs) are then fabricated via nanoprecipitation method, which demonstrate superior NIR-II imaging ability for in vivo vascular imaging and tumor-targeted imaging. Furthermore, O3 NPs exhibit significant photothermal performance, thus inducing obvious cancer cell elimination upon 808 nm light irradiation. Taken together, TBZ unit is a promising electron acceptor for constructing bright and functional NIR-II dyes. This acceptor engineering method has offered us a feasible strategy to develop versatile NIR-II fluorophores.

Fabrication of water-dispersible and cell-stimulating calcium phosphate nanoparticles immobilizing basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a therapeutic protein that can enhance angiogenesis, wound healing, and tissue regeneration; however, it is extremely unstable even under a normal physiological environment. Biocompatible calcium phosphate (CaP) nanoparticles (NPs) co-immobilizing bFGF, heparin, and ferucarbotran would be useful as a multifunctional delivery carrier of bFGF. In this study, such NPs were successfully fabricated by a coprecipitation process, using a labile supersaturated CaP solution containing bFGF, heparin, and ferucarbotran. The NPs showed relatively high negative zeta potential (-12mV) because of the negatively charged heparin, which enabled their stable dispersion in water. The hydrodynamic diameter of the NPs was around 200nm. Immunoreactive bFGF was released from the NPs in an acellular medium dose-dependently. The NPs promoted proliferation of baby hamster kidney fibroblasts (BHK-21 cells) and mouse osteoblastic MC3T3-E1 cells at a certain dose range, although they inhibited proliferation of rat pheochromocytoma (PC-12) cells. These results demonstrated that the effect of the NPs on cell proliferation was dependent on the cell type and dose, the details of which should be investigated in a future study.