NIR-vis-Induced pH-Sensitive TiO2 Immobilized Carbon Dot for Controllable Membrane-Nuclei Targeting and Photothermal Therapy of Cancer Cells.

This study investigated a selective and sensitive theragnosis system for the specific targeting of the membrane and nuclei based on visible-light and pH-responsive TiO2-integrated cross-linked carbon dot (C-CD/TiO2) for tumor detection and controllable photothermal therapy. The cross-linking system was formed by boronate ester linkages between the TiO2-immobilized Dopa-decyl (D-CD) and zwitterionic-formed CD (Z-CD) for nuclear targeting, which showed fluorescence "off" at physiological pH. The fluorescence recovered to the "on" state in acidic cancer cells owing to cleavages of the boronate ester bonds, resulting in the disruption of the Förster resonance energy transfer that generated different CDs useful for tumor-selective biosensors and therapy. D-CD, which is hydrophobic, can penetrate the hydrophobic sites of the cell membrane; it caused a loss in the hydrophobicity of these sites after visible-light irradiation. This was achieved by the photocatalytic activity of the TiO2 modulating energy bandgap, whereas the Z-CD targeted the nucleus, as confirmed by merged confocal microscopy images. D-CD augmented by photothermal heat also exhibited selective anticancer activity in the acidic tumor condition but showed only minimal effects at a normal site at pH 7.4. After C-CD/TiO2 injection to an in vivo tumor model, C-CD/TiO2 efficiently ablated tumors under NIR light irradiation. The C-CD/TiO2 group showed up-regulation of the pro-apoptotic markers such as P53 and BAX in tumor. This material exhibited its potential as a theragnostic sensor with excellent biocompatibility, high sensitivity, selective imaging, and direct anticancer activity via photothermal therapy.

Reduction-Triggered Paclitaxel Release Nano-Hybrid System Based on Core-Crosslinked Polymer Dots with a pH-Responsive Shell-Cleavable Colorimetric Biosensor.

Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via π-π stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy.

Photothermal-modulated reversible volume transition of wireless hydrogels embedded with redox-responsive carbon dots.

The reversible volume transition of redox-responsive hydrogels by near-infrared (NIR) irradiation has recently attracted significant attention as a novel therapy matrix for tracking and treating cancer via stimuli-responsive fluorescence on/off with controllable volume transition via a wireless sensing system. Herein, a NIR-induced redox-sensitive hydrogel was synthesized by blending a hydrogel with IR825-loaded carbon dots (CD) to achieve enhanced mobility of nanoparticles inside a gel network, and reversible volume phase transitions remotely controlled by a smartphone application via the induction of different redox environments. The presence of CD-IR825 in the thermosensitive poly(N-isopropylacrylamide) hydrogel network imparted fluorescence, electronic and photothermal properties to the hydrogels, which resulted in volume shrinkage behavior of the hydrogel upon exposure to NIR laser irradiation due to the redox-sensitive CDs. Under the NIR on/off cycles, the photothermal temperature, fluorescence, and porous structure were reversed after turning off the NIR laser. The hydrogel responsiveness under GSH and NIR light was studied using a wireless device based on the changes in the resistance graph on a smartphone application, generating a fast and simple method for the investigation of hydrogel properties. The in vitro cell viabilities of the MDA-MB cancer cells incubated with the composite hydrogel in the presence of external GSH exhibited a higher photothermal temperature, and the cancer cells were effectively killed after the NIR irradiation. Therefore, the NIR-induced redox-responsive nanocomposite hydrogel prepared herein has potential for use in cancer treatment and will enable the study of nanoparticle motion in hydrogel networks under multiple stimuli via a wireless device using a faster and more convenient method.

High performance of electrochemical and fluorescent probe by interaction of cell and bacteria with pH-sensitive polymer dots coated surfaces.

Using pH-switchable fluorescent polymer dots (PD) by means of fluorescent, colorimetric, and electrochemical signals generated from surfaces coated with PD of zwitterionic structure provided a fast and easy method to assess their performance in mammalian cell and bacterial interactions. The PD-coated surfaces showed high sensitivity over a broad range of pH levels by switching reversibly zwitterionic states, which led to an excellent cellular resistance effect by inhibiting the attachment of nearly 95% of mammalian cells. Similarly, they exhibited a strong interaction with the negatively charged surfaces of bacteria, as observed in the fluorescence ON/OFF system. In addition, PD were employed to detect the attachment of mammalian and bacterial cells: we deposited PD on a screen-printed carbon electrode for cyclic voltammetry analysis. Notably, the presence of cells remarkably interfered with the current flow between the PD and the screen-printed carbon electrode surface by causing an impressive decline in both reduction-oxidation signals, implying the high sensitivity of the PD-coated surfaces to cells and bacteria in different pH environments. Therefore, as smart materials with high sensitivity, biocompatibility, selectivity, and accuracy, PD-coated surfaces represent a promising approach to visualizing and controlling biological cell attachment, thereby helping to avoid contamination in biomedical applications.

Photoluminescence-tunable fluorescent carbon dots-deposited silver nanoparticle for detection and killing of bacteria.

Innovative methods to detect and kill pathogenic bacteria have a pivotal role in the eradication of infectious diseases and the prevention of the growth of antibiotic-resistant bacteria. The combination of fluorescent carbon dots (FCDs) with silver nanoparticles (AgNPs) is an effective material for synergic detection and antimicrobial activity determination. However, the fluorescence quenching of the FCDs owing to an interaction with AgNP is a major limitation. In this study, we designed a system to utilize poly(vinylpyrrolidone) (PVP) and catechol chemistry (PVP@Ag:FCD) in order to avoid the fluorescence quenching of the FCD-AgNP combination due to Forster Resonance Energy Transfer (FRET). PVP@Ag:FCD exhibited bright fluorescence, which can be used for bacterial detection, through the promotion of electrostatic binding with the negatively-charged bacterial surface and generation of fluorescence quenching due to aggregation-induced quenching. Furthermore, the presence of silver nanoparticles in PVP@Ag:FCD produced an excellent bacteria killing efficiency against E. coli and S. aureus, even at low concentrations (0.1 mg/mL). In contaminated river water, the PVP@Ag:FCD system showed a simple, highly sensitive, and effective performance for both the detection and eradication of bacteria. Therefore, this system offers an auspicious method for the future detection and killing of bacteria.

pH/Redox-Triggered Photothermal Treatment for Cancer Therapy Based on a Dual-Responsive Cationic Polymer Dot.

In the present study, a pH/redox-responsive cationic polymer dot (CD) was successfully prepared for a near-infrared (NIR)-mediated, simultaneously controllable photothermal temperature guided imaging off/on system to monitor therapeutic delivery. Carbonized disulfide cross-linked branched polyethyleneimine (bPEI) was conjugated with folic acid (FA) as a targeting moiety and partially formed an ionic complex with anionic indocyanine green (ICG) to afford a bPEI-based CD (ICG-CD). This was responsive to mild reductive (glutathione, GSH) and acidic tumor conditions, which enabled the simultaneous biodegradation of those hydrophobic and complex sites. The ICG-CD internalized readily into the cytoplasm of cancer cells by a FA receptor and cationic-mediated endocytosis in the off state, whereas if ICG-CD met intracellular GSH at high concentrations, GSH contributed partially to the recovery of fluorescence and was then internalized into acidic endosomes to induce complete restoration of fluorescence. This tumor-sensitive degradability of the CD not only facilitated ICG release in the tumor location but also allowed controllable photothermal therapy effects of nanoparticles under NIR irradiation, which resulted in improved cancer therapy. Taken together, the results indicate great potential in tumor targeting, intracellular imaging, and controllable therapeutic delivery through a fluorescence off/on assay under the pH/redox conditions of cancer cells.