In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles.

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.

Trackable Liposomes for In Vivo Delivery Tracing toward Personalized Medicine Care under NIR Light on Skin Tumor.

We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and in vivo mouse veins after intravenous administration. The trackable liposome delivery provides in vitro and in vivo photothermal heat (∼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.

Local drug delivery from surgical thread for area-specific anesthesia.

The application of surgical suture-thread and the systemic analgesics regimens for pain control in the postoperative surgery remain the criterion standard. However, these medications have daunting adverse effects on the body's innate pain management system. To address this issue, we have developed a local analgesic-loaded suture system which could be efficiently used for surgical repair with localized sedation effect. The drug-loaded conventional suture has modified by adhesive poly-dopamine coating with the local anesthetic lidocaine. The surface modifications have been ascertained by FE-SEM imaging. The tensile strength of suture ensures required elasticity to use in surgical skin closure. In vitro drug release and the in vivo local analgesia was achieved one day after surgery and persisted approximately for one week in 80% of treated animals. Our pre-clinical results suggest that drug-loaded surgical thread may be an effective strategy for improving the overall outcome.

Surface patterned pH-sensitive fluorescence using ß-cyclodextrin functionalized poly(ethylene glycol).

This paper reports the development of a pH-responsive molecular pattern that shows specific and selective affinity for particular host-guest interactions, and its use as a pH fluorescent sensor. The pH-responsive boronate ester is formed via interactions between the diol group of ß-cyclodextrin (CD) and phenylboronic acid of poly(ethylene glycol), and is strategically designed to allow reversible formation of a molecular lining pattern. Printing on a versatile substrate provides a method to monitor the positioning of different molecules by using a pH-responsive boronate ester, allowing specific host-guest interactions on any surface. Confocal laser scanning microscopy, fluorescence spectroscopy, and (1)H NMR results indicate that the assembled CD monolayer can be removed by washing with an acidic pH buffer, demonstrating the presence of a boronate ester connective bridge, which is acid labile. Therefore, visualization of the pH-responsive fluorescence sensor using a rhodamine-CD complex allows straightforward discrimination between different molecules on any substrate, thus facilitating application of this sensor in clinical diagnostics and environmental monitoring.

Iron Oxide@PEDOT-Based Recyclable Photothermal Nanoparticles with Poly(vinylpyrrolidone) Sulfobetaines for Rapid and Effective Antibacterial Activity.

Growing microbial resistance that renders antibiotic treatment vulnerable has emerged, attracting a great deal of interest in the need to develop alternative antimicrobial treatments. To contribute to this effort, we report magnetic iron oxide (Fe3O4) nanoparticles (NPs) coated with catechol-conjugated poly(vinylpyrrolidone) sulfobetaines (C-PVPS). This negatively charged Fe3O4@C-PVPS is subsequently encapsulated by poly(3,4-ethylenedioxythiophene) (PEDOT) following a layer-by-layer (LBL) self-assembly method. The obtained Fe3O4@C-PVPS:PEDOT nanoparticles appear to be novel NIR-irradiated photothermal agents that can achieve effective bacterial killing and are reusable after isolation of the used particles using external magnetic fields. The recyclable Fe3O4@C-PVPS:PEDOT NPs exhibit a high efficiency in converting photothermal heat for rapid antibacterial effects against Staphylococcus aureus and Escherichia coli. In this study, antibacterial tests for repeated uses maintained almost 100% antibacterial efficiency during three cycles and provided rapid and effective killing of 99% Gram-positive and -negative bacteria within 5 min of near-infrared (NIR) light exposure. The core-shell nanoparticles (Fe3O4@C-PVPS:PEDOT) exhibit the required stability, and their paramagnetic nature means that they rapidly convert photothermal heat sufficient for use as NIR-irradiated antibacterial photothermal sterilizing agents.

pH triggered in vivo photothermal therapy and fluorescence nanoplatform of cancer based on responsive polymer-indocyanine green integrated reduced graphene oxide.

We have synthesized a pH-dependent, NIR-sensitive, reduced graphene oxide (rGO) hybrid nano-composite via electrostatic interaction with indocyanine green (ICG) which is designed not only to destroy localized cancer cells but also be minimally invasive to surrounding normal cells. The near-infrared (NIR) irradiated hybrid nano-composites showed pH dependent photo-thermal heat generation capability from pH 5.0 to 7.4 due to the pH response relief and quenching effects of poly(2-dimethyl amino ethyl methacrylate) [poly(PDMAEMA)] with ICG on a single rGO sheet. This pH-triggered relief and quenching mechanism regulated in vitro photo-thermolysis as the pH changed from 5.0 to 7.4. The in vitro cellular uptake and confocal laser scan microscopic (CLSM) images at different pH values show promise for environment sensitive bio-imaging. The NIR-absorbing hybrid nanomaterials showed a remarkably improved in vitro cancer cell targeted photothermal destruction compared to free ICG. Upon local NIR irradiation, these hybrid nano-composites-treated tumors showed necrotic, shrunken, ablation of malignant cells and totally healed after 18 days treatment. Our finding regarding the acidic pH stimulus of cancer cellular environment has proven to be a wining platform for the fight against cancer.

In situ synthesis of luminescent carbon nanoparticles toward target bioimaging.

This paper describes the in situ synthesis of single fluorescence carbon nanoparticles (FCNs) for target bioimaging applications derived from biocompatible hyaluronic acid (HA) without using common conjugation processes. FCNs formed via the dehydration of hyaluronic acid, which were obtained by carbonizing HA, and partially carbonized HA fluorescence carbon nanoparticles (HA-FCNs), formed by a lower degree of carbonization, show good aqueous solubility, small particle size (<20 nm) and different fluorescence intensities with a red shift. After confirming the cytotoxicity of HA-FCNs and FCNs, we carried out in vitro and in vivo bioimaging studies where HA-FCNs themselves functioned as single particle triggers in target imaging. The converted nanocrystal carbon particles from HA provide outstanding features for in vitro and in vivo new targeted delivery and diagnostic tools.

Photo- and pH-tunable multicolor fluorescent nanoparticle-based spiropyran- and BODIPY-conjugated polymer with graphene oxide.

We report a stimuli-responsive fluorescent nanomaterial, based on graphene oxide coupled with a polymer conjugated with photochromic spiropyran (SP) dye and hydrophobic boron dipyrromethane (BODIPY) dye, for application in triggered target multicolor bioimaging. Graphene oxide (GO) was reduced by catechol-conjugated polymers under mildly alkaline conditions, which enabled to formation of functionalized multicolor graphene nanoparticles that can be induced by irradiation with UV light and by changing the pH from acidic to neutral. Investigation of these nanoparticles by using AFM, fluorescence emission, and in vitro cell and in vivo imaging revealed that they show different tunable colors in bioimaging applications and, more specifically, in cancer-cell detection. The stability, biocompatibility, and quenching efficacy of this nanocomposite open a different perspective for cell imaging in different independent colors, sequentially and simultaneously.