pH-Responsive NIR-Absorbing Fluorescent Polydopamine with Hyaluronic Acid for Dual Targeting and Synergistic Effects of Photothermal and Chemotherapy

In cancer therapy, optimizing tumor-specific delivery, tumor distribution, and cellular uptake of a drug is important for ensuring minimal toxicity and maximum therapeutic efficacy. This study characterized the therapeutic efficacy of a stimulus responsive and dual targeting nanocarrier for a bioimaging-guided photothermal and chemotherapeutic platform. Hyaluronic acid (HA) conjugated with triphenylphosphonium (TPP) and boronic acid (BA) diol-linked β-cyclodextrin (β-CD) forms an inclusion complex with paclitaxel (PTX), creating a shell-like composite on a core of carbonized fluorescent polydopamine nanoparticles (FNPs-pDA) applicable for photothermal therapy as well as bioimaging. The successful diol cross-linking between core@shells generates nanocarriers [FNPs-pDA@HA-TPP-CD-PTX] that can be used as an extracellular HA- and intracellular TPP-mediated dual targeting system. The carbonized FNPs-pDA was cross-linked with the boronic acid groups of HA-TPP-CD-PTX to promote the formation of boronate esters for pH-mediated photothermal activity, which have shown time dependent complete PTX release along with a photothermal mediated response. The in vitro dual bioimaging and photothermal-chemotherapeutic activities were compared between cancer and normal cells. Lysosomal escape and live/dead cells staining confocal images highlight the promise of this system, which might open up a new approach, a simple and versatile method for site-specific synergetic drug delivery

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 <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. 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

Photoresponsive Fluorescent Reduced Graphene Oxide by Spiropyran Conjugated Hyaluronic Acid for in Vivo Imaging and Target Delivery

This present article demonstrates the strategy to prepare photoresponsive reduced graphene oxide with mussel inspired adhesive material dopamine (DN) and photochromic dye spiropyran (SP) conjugated to the backbone of the targeting ligand hyaluronic acid (HA; HA-SP). Graphene oxide (GO) was reduced by prepared HA-SP accepting the advantages of catechol chemistry under mildly alkaline condition enabling to achieve functionalized graphene (rGO/HA-SP) as fluorescent nanoparticles. Due to containing HA, rGO/HA-SP can bind to the CD44 cell receptors. The prepared rGO/HA-SP is able to retain its photochromic features and can be converted to merocyanine (MC) form upon irradiation with UV light (wavelength: 365 nm) displaying purple color. Photochromic behavior of rGO/HA-SP was monitored by UV–vis and fluorescence spectroscopy. In vitro fluorescence behavior, examined by confocal laser scanning microscope (CLSM), of rGO/HA-SP in cancerous A549 cell lines assured that efficient delivery of rGO/HA-SP was gained due to HA as targeting ligand. In this work, we have shown that in vivo fluorescence image of spiropyran is possible by administrating MC form solution of rGO/HA-SP using Balb/C mice as in vivo modal. Accumulation of rGO/HA-SP in tumor tissue from biodistribution analysis strongly supports the specific delivery of prepared graphene to the target destination. The well tuned drug release manner from the surface of rGO/HA-SP strongly recommends the developed material not only as fluorescent probe for diagnosis but also as a drug carrier in drug delivery system

Light Controllable Surface Coating for Effective Photothermal Killing of Bacteria

Although the electronic properties of conducting films have been widely explored in optoelectronic fields, the optical absorption abilities of surface-coated films for photothermal conversion have been relatively less explored in the production of antibacterial coatings. Here, we present catechol-conjugated poly­(vinylpyrrolidone) sulfobetaine (PVPS) and polyaniline (PANI) tightly linked by ionic interaction (PVPS:PANI) as a novel photothermal antibacterial agent for surface coating, which can absorb broadband near-infrared (NIR) light. Taking advantage of the NIR light absorption, this coating film can release eminent photothermal heat for the rapid killing of surface bacteria. The NIR light triggers a sharp rise in photothermal heat, providing the rapid and effective killing of 99.9% of the Gram-positive and -negative bacteria tested within 3 min of NIR light exposure when used at the concentration of 1 mg/mL. Although considerable progress has been made in the design of antibacterial coatings, the user control of NIR-irradiated rapid photothermal destruction of surface bacteria holds increasing attention beyond the traditional boundaries of typical antibacterial surfaces

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)-<i>g</i>-poly­(dimethylaminoethyl methacrylate) (PEG-<i>g</i>-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

Determination of Cancer Cell-Based pH-Sensitive Fluorescent Carbon Nanoparticles of Cross-Linked Polydopamine by Fluorescence Sensing of Alkaline Phosphatase Activity on Coated Surfaces and Aqueous Solution

The tumor-specific sensitive fluorescence sensing of cellular alkaline phosphatase (ALP) activity on the basis of host–guest specific and pH sensitivity was conducted on coated surfaces and aqueous states. Cross-linked fluorescent nanoparticles (C-FNP) consisting of β-cyclodextrin (β-CD)/boronic acid (BA) and fluorescent hyaluronic acid [FNP­(HA)] were conjugated to fluorescent polydopamine [FNP­(pDA)]. To determine the quenching effect of this system, hydrolysis of 4-nitrophenyl phosphate (NPP) to 4-nitrophenol (NP) was performed in the cavity of β-CD in the presence of ALP activated photoinduced electron transfer (PET) between NP and C-FNP. At an ALP level of 30–1000 U/L, NP caused off-emission of C-FNP because of their specific host–guest recognition. Fluorescence can be recovered under pH shock due to cleavage of the diol bond between β-CD and BA, resulting in release of NP from the fluorescent system. Sensitivity of the assays was assessed by confocal imaging not only in aqueous states, but also for the first time on coated surfaces in MDAMB-231 and MDCK cells. This novel system demonstrated high sensitivity to ALP through generation of good electron donor/acceptor pair during the PET process. Therefore, this fluorescence sensor system can be used to enhance ALP monitoring and cancer diagnosis on both coated surfaces and in aqueous states in clinical settings

Simple Microwave-Assisted Synthesis of Amphiphilic Carbon Quantum Dots from A₃/B₂ Polyamidation Monomer Set

Highly fluorescent and amphiphilic carbon quantum dots (CQDs) were prepared by microwave-assisted pyrolysis of citric acid and 4,7,10-trioxa-1,13-tridecanediamine (TTDDA), which functioned as an A₃ and B₂ polyamidation type monomer set. Gram quantities of fluorescent CQDs were easily obtained within 5 min of microwave heating using a household microwave oven. Because of the dual role of TTDDA, both as a constituting monomer and as a surface passivation agent, TTDDA-based CQDs showed a high fluorescence quantum yield of 29% and amphiphilic solubility in various polar and nonpolar solvents. These properties enable the wide application of TTDDA-based CQDs as nontoxic bioimaging agents, nanofillers for polymer composites, and down-converting layers for enhancing the efficiency of Si solar cells

Visible-Light-Driven Photocatalysts of Perfluorinated Silica-Based Fluorescent Carbon Dot/TiO₂ for Tunable Hydrophilic–Hydrophobic Surfaces

In this study, a new hydrophilic–hydrophobic transition surface was designed via visible-light-induced photocatalytic perfluorinated silica-based fluorescent carbon nanoparticles (FNPs)/TiO₂. Perfluorinated silica–polydopamine hybrid FNPs (<i>f</i>-FNPs) were easily fabricated by carbonization in an emulsion system consisting of tetraethyl orthosilicate and dopamine, followed by the deposition of TiO₂ on <i>f</i>-FNPs, which demonstrated the reversal from hydrophobic to hydrophilic nature during successful photocatalysis. The synergistic effect of silica–carbon and the deposited TiO₂ NPs led to the decomposition of methylene blue under UV and visible light irradiation, demonstrating that FNPs/TiO₂ sustains photocatalytic activity. The profound contact angle with the catalytic kinetics curve and precise morphology and extension of cells detach antifouling exceptionally unrestricted the synergistic effect of silica–carbon on TiO₂ NPs on a coated paper substrate. Given the interest in the manipulation of hydrophobicity and hydrophilicity, this study can serve as a guideline for the fabrication of photocatalytic surfaces where water spreads completely

<i>In Vivo</i> Biodistribution and Toxicology of Carboxylated Graphene Quantum Dots

Photoluminescent graphene quantum dots (GQDs) have fascinating optical and electronic properties with numerous promising applications in biomedical engineering. In this work, we first studied the <i>in vivo</i> biodistribution and the potential toxicity of carboxylated photoluminescent GQDs. KB, MDA-MB231, A549 cancer cells, and MDCK normal cell line were chosen as <i>in vitro</i> cell culture models to examine the possible adverse effects of the carboxylated photoluminescent GQDs. The carboxylated GQDs are desirable for increased aqueous solubility. All cancer cells efficiently took up the carboxylated GQDs. No acute toxicity or morphological changes were noted in either system at the tested exposure levels. A long-term <i>in vivo</i> study revealed that the GQDs mainly accumulated in liver, spleen, lung, kidney, and tumor sites after intravenous injection. To reveal any potential toxic effect of the GQDs on treated mice, serum biochemical analysis and histological evaluation were performed. The toxicity results from serum biochemistry and complete blood count study revealed that the GQDs do not cause appreciable toxicity to the treated animals. Finally, we observed no obvious organ damage or lesions for the GQDs treated mice after 21 days of administration at 5 mg/kg or 10 mg/kg dosages. With adequate studies of toxicity, both <i>in vitro</i> and <i>in vivo</i>, photoluminescent GQDs may be considered for biological application

Highly Efficient Visible Blue-Emitting Black Phosphorus Quantum Dot: Mussel-Inspired Surface Functionalization for Bioapplications

The preparation of blue-emitting black phosphorus quantum dots (BPQDs) is based on the liquid-phase exfoliation of bulk BP. We report the synthesis of soluble BPQDs showing a strong visible blue-light emission. Highly fluorescent (photoluminescence quantum yield of ≈5% with the maximum emission (λ_max) at ≈437 nm) and dispersible BPQDs in various organic solvents are first prepared by simple ultrasonication of BP crystals in chloroform in the ambient atmosphere. Furthermore, simple mussel-inspired surface functionalization of BPQDs with catechol-grafted poly­(ethylene glycol) in basic buffer afforded water-soluble blue-emitting BPQDs showing long-term fluorescence stability, very low cytotoxicity, and excellent fluorescence live cell imaging capability