Minimizing the Heat Effect of Photodynamic Therapy Based on Inorganic Nanocomposites Mediated by 808 nm Near-Infrared Light.

Photodynamic therapy (PDT) based on photosensitizers (PSs) constructed with nanomaterials has become popular in cancer treatment, especially oral carcinoma cell. This therapy is characterized by improved PS accumulation in tumor regions and generation of reactive oxygen species (ROS) for PDT under specific excitation. In the selection of near-infrared (NIR) window, 808 nm NIR light because it can avoid the absorption of water is particularly suitable for the application in PDT. Hence, multiband emissions under a single 808 nm near-infrared excitation of Nd3+ -sensitized upconversion nanoparticles (808 nm UCNPs) have been applied for the PDT effect. 808 nm UCNPs serve as light converter to emit UV light to excite inorganic PS, graphitic carbon nitride quantum dots (CNQDs), thereby generating ROS. In this study, a nanocomposite consisting UCNPs conjugated with poly-l-lysine (PLL) to improve binding with CNQDs is fabricated. According to the research results, NIR-triggered nanocomposites of 808 nm UCNP-PLL@CNs have been verified by significant improvement in ROS generation. Consequently, 808 nm UCNP-PLL@CNs exhibit high capability for ROS production and efficient PDT in vitro and in vivo. Moreover, the mechanism of PDT treatment by 808 nm UCNP-PLL@CNs is evaluated using the cell apoptosis pathway.

Near-Infrared Light-Mediated Photodynamic Therapy Nanoplatform by the Electrostatic Assembly of Upconversion Nanoparticles with Graphitic Carbon Nitride Quantum Dots.

Photodynamic therapy (PDT) is a promising antitumor treatment that is based on photosensitizers. This therapy kills cancer cells by generating reactive oxygen species (ROS) after irradiation with specific laser wavelengths. Being a potential photosensitizer, graphitic carbon nitride (g-C3N4) quantum dots (QDs) are noncytotoxic. Although the use of g-C3N4 QDs is challenged by the limited tissue penetration of UV light, g-C3N4 QDs display excellent ultraviolet (UV) light-triggered cytotoxicity. The g-C3N4 QDs were synthesized using a solid-phase hydrothermal method. The well-distributed hydrophilic g-C3N4 can be combined with NaYF4:Yb3+/Tm3+ upconversion nanoparticles via the positive ligand poly(l-lysine) to produce the final nanocomposite, NaYF4:Yb/Tm-PLL@g-C3N4. Upconversion nanoparticles can transfer IR light into UV light and promote g-C3N4 to release blue-to-green visible light to generate different images. Moreover, g-C3N4 is a promising photosensitizer in PDT because g-C3N4 can transfer oxygen into toxic ROS. The singlet oxygen formed by g-C3N4 displays great potential for use in the treatment of cancer.

Erratum: Near-Infrared-Activated Fluorescence Resonance Energy Transfer-Based Nanocomposite to Sense MMP2-Overexpressing Oral Cancer Cells.

[This corrects the article DOI: 10.1021/acsomega.7b01494.].

Near-Infrared-Activated Fluorescence Resonance Energy Transfer-Based Nanocomposite to Sense MMP2-Overexpressing Oral Cancer Cells.

The matrix metalloproteinases (MMPs) are well-known mediators that are activated in tumor progression. MMP2 is a kind of gelatinase in extracellular matrix remodeling and cancer metastasis processes. MMP2 secretion increased in many types of cancer diseases, and its abnormal expression is associated with a poor prognosis. We fabricated a nanocomposite that sensed MMP2 expression by a red and blue light change. This nanocomposite consisted of an upconversion nanoparticle (UCNP), MMP2-sensitive peptide, and CuInS2/ZnS quantum dot (CIS/ZnS QD). An UCNP is composed of NaYF4:Tm/Yb@NaYF4:Nd/Yb, which has multiple emissions at UV/blue-visible wavelengths under 808 nm laser excitation. The conjugated CIS/ZnS QD showed the red-visible fluorescence though the FRET process. The two fluorophores were connected by a MMP2-sensitive peptide to form a novel MMP2 biosensor, named UCNP@p-QD. UCNP@p-QD was highly biocompatible according to cell viability assay. The FRET-based biosensor was employed in the MMP2 determination in vitro and in vivo. Furthermore, it was administrated into the tumor-bearing mouse to check MMP2 expression. UCNP@p-QD could be a promising tool for biological study and biomedical application. In this study, we demonstrated that the CIS/ZnS QD improved the upconversion intensity through a near-infrared-induced FRET process. This nanocomposite has the advantage of light penetration, excellent biocompatibility, and high sensitivity to sense MMP2. The near-infrared-induced composites are a potential inspiration for use in biomedical applications.

Plasmon-Enhanced Photodynamic Cancer Therapy by Upconversion Nanoparticles Conjugated with Au Nanorods.

Photodynamic therapy (PDT) based on photosensitizers (PSs) constructed with nanomaterials has been widely applied to treat cancer. This therapy is characterized by an improved PS accumulation in tumor regions. However, challenges, such as short penetration depth of light and low extinction coefficient of PSs, limit PDT applications. In this study, a nanocomposite consisting of NaYF4:Yb/Er upconversion nanoparticles (UCPs) conjugated with gold nanorods (Au NRs) was developed to improve the therapeutic efficiency of PDT. Methylene blue (MB) was embedded in a silica shell for plasmon-enhanced PDT. UCPs served as a light converter from near-infrared (NIR) to visible light to excite MB to generate reactive oxygen species (ROS). Au NRs could effectively enhance upconversion efficiency and ROS content through a localized surface plasmon resonance (SPR) effect. Silica shell thickness was adjusted to investigate the optimized MB loading amount, ROS production capability, and efficient distance for plasmon-enhanced ROS production. The mechanism of plasmon-enhanced PDT was verified by enhancing UC luminescence intensity through the plasmonic field and by increasing the light-harvesting capability and absorption cross section of the system. This process improved the ROS generation by comparing the exchange of Au NRs to Au nanoparticles with different SPR bands. NIR-triggered nanocomposites of UCP@SiO2:MB-NRs were significantly confirmed by improving ROS generation and further modifying folic acid (FA) to develop an active component targeting OECM-1 oral cancer cells. Consequently, UCP@SiO2:MB-NRs-FA could highly produce ROS and undergo efficient PDT in vitro and in vivo. The mechanism of PDT treatment by UCP@SiO2:MB-NRs-FA was evaluated via the cell apoptosis pathway. The proposed process is a promising strategy to enhance ROS production through plasmonic field enhancement and thus achieve high PDT therapeutic efficacy.

Evaluation of the intracellular uptake and cytotoxicity effect of TiO2 nanostructures for various human oral and lung cells under dark conditions.

Titanium dioxide (TiO2) nanomaterials (NMs) have been widely used to develop commercial products such as sunscreen cosmetics because of their unique optical properties to provide complete protection from ultraviolet (UV) light. The most dangerous type of UV radiation is UVA, which comprises nearly 97% of the UV radiation that reaches the Earth. This type of radiation is also the major cause of skin damage. As the most beneficial content of sunscreen cosmetics, TiO2 NMs exhibit immense capability to protect the human skin from UVA exposure through their scattering and reflecting physical properties. Therefore, investigating the factors involved in using TiO2 NMs in cosmetics is necessary. In this study, various human oral and lung cell lines were selected to evaluate the cytotoxicity of treatment using different sizes and shapes of TiO2 NMs, including spheres (AFDC and AFDC300) and rods (M212 and cNRs). The morphology, size, and crystalline phase of the selected TiO2 NMs were studied to characterize each physical property. Based on cell viability and endocytic behavior results, treatment with all the selected TiO2 NMs were nearly non-toxic to the oral cell lines. However, high cytotoxicity was obviously observed in lung cells with M212 and AFDC treatments at 50 µg mL-1, which was larger by approximately 20% than with ADC300 and cNRs treatments because the smaller the TiO2 NMs, the larger their specific surface area. This condition resulted in the progress of apoptosis from the considerable aggregation of TiO2 NMs in the cytoplasm. Moreover, compared with those of TiO2 NMs with a similar structure (e.g., cNRs) and size (e.g., M212), the cellular uptake of AFDC was evidently low, which resulted in the approximated non-toxicity. Moreover, the similar sizes and different shapes of AFDC and cNRs were considered to treat lung cells to investigate further the influence of morphology on the cell cycle and the apoptosis effect. Consequently, AFDC and cNRs could inhibit the growth of lung cells and allow a considerable proportion of the cells to remain in the G1/G0 phase. Furthermore, a high-dose treatment would directly induce the apoptosis pathway, whereas a low-dose treatment might decrease cell regeneration.

MMP2-sensing up-conversion nanoparticle for fluorescence biosensing in head and neck cancer cells.

Upconversion nanoparticles (UCNPs) have extensive biological-applications because of their bio-compatibility, tunable optical properties and their ability to be excited by infrared radiation. Matrix metalloproteinases (MMPs) play important roles in extracellular matrix remodelling; they are usually found to significantly increase during cancer progression, and these increases may lead to poor patient survival. In this study, we produced a biosensor that can be recognized by MMP2 and then be unravelled by the attached quencher to emit visible light. We used 3.5-nm gold nanoparticles as a quencher that absorbed emission from UCNPs at a wavelength of 540 nm. The biosensor consists of an upconversion nanoparticle, MMP2-recognized polypeptides and quenchers. Here, UCNPs consisting of NaYF4:Yb(3+)/Er(3+) were prepared via a high temperature co-precipitation method while protecting the oleic acid ligand. To improve the biocompatibility and modify the UCNPs with a polypeptide, they were coated with a silica shell and further conjugated with MMP-recognizing polypeptides. The polypeptide has two ends of featuring carboxylic and thiol groups that react with UCNPs and AuNPs, and the resulting nanoparticles were referred to as UCNP@p-Au. According to the in vitro cell viability analysis, UCNP@p-Au exhibited little toxicity and biocompatibility in head and neck cancer cells. Cellular uptake studies showed that the MMP-based biosensor was activated by 980-nm irradiation to emit green light. This MMP-based biosensor may serve as sensitive and specific molecular fluorescent probe in biological-applications.

Quantifying the barrier lowering of ZnO Schottky nanodevices under UV light.

In this study we measured the degrees to which the Schottky barrier heights (SBHs) are lowered in ZnO nanowire (NW) devices under illumination with UV light. We measured the I-V characteristics of ZnO nanowire devices to confirm that ZnO is an n-type semiconductor and that the on/off ratio is approximately 10(4). From temperature-dependent I-V measurements we obtained a SBH of 0.661 eV for a ZnO NW Schottky device in the dark. The photosensitivity of Schottky devices under UV illumination at a power density of 3 µW/cm(2) was 9186%. Variations in the SBH account for the superior characteristics of n-type Schottky devices under illumination with UV light. The SBH variations were due to the coupled mechanism of adsorption and desorption of O2 and the increase in the carrier density. Furthermore, through temperature-dependent I-V measurements, we determined the SBHs in the dark and under illumination with UV light at power densities of 0.5, 1, 2, and 3 µW/cm(2) to be 0.661, 0.216, 0.178, 0.125, and 0.068 eV, respectively. These findings should be applicable in the design of highly sensitive nanoscale optoelectronic devices.

Plasmon-induced hyperthermia: hybrid upconversion NaYF4:Yb/Er and gold nanomaterials for oral cancer photothermal therapy.

Nanocomposites consisting of upconversion nanoparticles (UCPs) and plasmonic materials have been widely explored for bio-imaging and cancer photothermal therapy (PTT). However, several challenges, including incomprehensible efficiency of energy transfer processes and optimization of the conditions for plasmon-induced photothermal effects, still exist. In this study, we fabricated NaYF4:Yb3+/Er3+ nanoparticles (NPs) conjugated with gold nanomaterials (Au NMs), such as Au NPs and gold nanorods (Au NRs). NaYF4:Yb3+/Er3+ NPs were used as photoconverters, which could emit green and red light under excitation of a 980 nm laser; Au NPs and Au NRs were also prepared and used as heat producers. The silica shell was further coated around UCPs to improve biocompatibility and as a bridge linking UCPs and the Au NMs. Most importantly, the thickness of the silica shell was tuned precisely to investigate the effective distance of the plasmonic field for heat induction. Energy transfer was confirmed by the declining UCL photoluminescence and emission decay time after connecting to the Au NMs. Moreover, a simulative model was built using the finite element method to assess the differences in heat generation between UCP@SiO2-NPs and UCP@SiO2-NRs. The surfaces of the hybrid nanocomposites were modified with folic acid to improve the specific targeting to cancer cells. The performance of the modified hybrid nanocomposites in PTT for OECM-1 oral cancer cells was evaluated.

Non-amine-based furan-containing oligoaryls as efficient hole transporting materials.

A new class of highly stable furan-based hole transporting oligomeric materials, synthesized from the corresponding propargylic dithioacetals, serve as efficient hole transporting materials in electroluminescent devices. The performance of the devices using these furan materials is comparable with or somewhat better than those employing the conventional triarylamines (e.g. alpha-NPD).

First examples of organophosphorus-containing materials for light-emitting diodes.

Exploiting the reactivity of the P-atom of phosphole-based oligomers, we have achieved access to the first organophosphorus-containing organic light-emitting diode (OLED) materials. The versatility of these P-materials is demonstrated with the synthesis of a corresponding gold complex that has also been used as an OLED material. Optimization of the OLED devices by doping the phosphole layer with a red fluorescent dye is described.