Glutathione Depletion in a Benign Manner by MoS2‐Based Nanoflowers for Enhanced Hypoxia‐Irrelevant Free‐Radical‐Based Cancer Therapy

Tumor hypoxia significantly diminishes the efficacy of reactive oxygen species (ROS)‐based therapy, mainly because the generation of ROS is highly oxygen dependent. Recently reported hypoxia‐irrelevant radical initiators (AIBIs) exhibit promising potential for cancer therapy under different oxygen tensions. However, overexpressed glutathione (GSH) in cancer cells would potently scavenge the free radicals produced from AIBI before their arrival to the specific site and dramatically limit the therapeutic efficacy. A synergistic antitumor platform (MoS₂@AIBI‐PCM nanoflowers) is constructed by incorporating polyethylene‐glycol‐functionalized molybdenum disulfide (PEG‐MoS₂) nanoflowers with azo initiator and phase‐change material (PCM). Under near‐infrared laser (NIR) irradiation, the photothermal feature of PEG‐MoS₂ induces the decomposition of AIBI to produce free radicals. Furthermore, PEG‐MoS₂ can facilitate GSH oxidation without releasing toxic metal ions, greatly promoting tumor apoptosis and avoiding the introduction of toxic metal ions. This is the first example of the use of intelligent MoS₂‐based nanoflowers as a benign GSH scavenger for enhanced cancer treatment.     

Polyethylene Glycol and Polyethylenimine Dual‐Functionalized Nano‐Graphene Oxide for Photothermally Enhanced Gene Delivery

Graphene oxide (GO) has been extensively explored in nanomedicine for its excellent physiochemical, electrical, and optical properties. Here, polyethylene glycol (PEG) and polyethylenimine (PEI) are covalently conjugated to GO via amide bonds, obtaining a physiologically stable dual‐polymer‐functionalized nano‐GO conjugate (NGO‐PEG‐PEI) with ultra‐small size. Compared with free PEI and the GO‐PEI conjugate without PEGylation, NGO‐PEG‐PEI shows superior gene transfection efficiency without serum interference, as well as reduced cytotoxicity. Utilizing the NIR optical absorbance of NGO, the cellular uptake of NGO‐PEG‐PEI is shown to be enhanced under a low power NIR laser irradiation, owing to the mild photothermal heating that increases the cell membrane permeability without significantly damaging cells. As the results, remarkably enhanced plasmid DNA transfection efficiencies induced by the NIR laser are achieved using NGO‐PEG‐PEI as the light‐responsive gene carrier. More importantly, it is shown that our NGO‐PEG‐PEI is able to deliver small interfering RNA (siRNA) into cells under the control of NIR light, resulting in obvious down‐regulation of the target gene, Polo‐like kinase 1 (Plk1), in the presence of laser irradiation. This study is the first to use photothermally enhanced intracellular trafficking of nanocarriers for light‐controllable gene delivery. This work also encourages further explorations of functionalized nano‐GO as a photocontrollable nanovector for combined photothermal and gene therapies.     

Why does nitrogen-doped graphene oxide lose the antibacterial activity?

Graphene and its derivatives attract extensive research interests in the biomedicine field due to their outstanding physiochemical properties.Lots of studies have reported that graphene materials exhibit antibacterial activities.However,antibacterial mechanisms of graphene materials still remain controversial and need further investigation.Herein,graphene oxide(GO)with and without nitrogen-doping were fabricated on the titanium surface by cathodic electro phoretic deposition and antibacterial activities were systematically investigated.Results showed that GO on the titanium surface presented antibacterial activity,while nitrogen-doped GO lost the antibacterial activity.The reason is that antibacterial mechanisms for the GO-metal system contain two steps.First,electron transfer occurs from bacterium's cell membrane to GO surface which destroys the bacterial respiratory chain;subsequently,electrons on GO surface induce the production of reactive oxygen species(ROS)that damage the membrane structure and eventually lead to bacterial death.For nitrogen-doped GO,nitrogen atoms denote electrons into GO leading to n-type doping.Nitrogen-doped GO as an electron donor cuts off the electron transfer from the cell membrane to GO and subsequently inhibits the production of ROS.This is why nitrogen-doped GO exhibits no antibacterial activity.This work confirms the antibacterial mecha nisms for the GO-metal system with a synergistic effect of non-oxidative electron transfer and ROS mediated oxidative stress.     

Radikalidentifizierung auf Polymeren nach Plasmabehandlung. Radical Identification on Polymers after Plasma Treatment

Radicals form the initial germ for reactions of chemically inert polymers. The incorporation of functional chemical groups can proceed via trapping‐ or quenching reactions of polymer radicals with functionalized reaction partners. The density of surfaces radicals governs the efficiency of the surface functionalization process. Subsequent to its termination, the surviving radicals become of special importance since they can react with oxygen from air. This may introduce an unintended secondary functionalization of the polymer surface with various oxygen groups. Therefore, the identification and quantification of radicals on polymer surfaces is becoming increasingly important for the on‐going development of highly efficient and highly selective functionalization of polymer surface. Here, we present currently most relevant methods for surface radical quantification. In addition, a new approach to the generation of radicals on polymer surface is presented.     

A UV-light induced photochemical method for graphene oxide reduction

Chemical reduction of graphene oxide (GO) has been considered as a promising route towards the large scale production of graphene. Herein, a rapid, efficient photochemical method for preparing reduced graphene oxide (RGO) by ultraviolet (UV) irradiation of a mixture solution containing a photoinitiator and Monoethanolamine (MEA) compound in ethanol has been developed. In this route, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (GR-XBPO) was used as the reductant and MEA as the oxygen inhibition agent. After UV irradiation, oxygen-containing groups (OCGs) on GO plane and edges are being largely removed due to the reduction of GO by free radicals generated by photoinitiator decomposition. X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet and visible spectrophotometer showed that GR-XBPO can efficiently reduce GO at room temperature. It is also found that the electrical conductivity of RGO fabricated by this rapid route (~10 min) is more competitive compared to other reported works. Moreover the corresponding reduction mechanism was being discussed. This work puts forward a novel method for preparing graphene, and has great potential in scaling up graphene production and developing graphene materials.     

Integration of IR‐808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR‐excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR‐808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)‐functionalized silica layer is developed for PDT agent. The two booster effectors (dye‐sensitization and core–shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS₂ nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS₂ nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.     

Targeted luminescent near-infrared polymer-nanoprobes for in vivo imaging of tumor hypoxia

Polystyrene nanoparticles (PS-NPs) were doped with an oxygen-sensitive near-infrared (NIR)-emissive palladium meso-tetraphenylporphyrin and an inert reference dye which are both excitable at 635 nm. The nanosensors were characterized with special emphasis on fundamental parameters such as absolute photoluminescence quantum yield and fluorescence lifetime. The PS-NPs were employed for ratiometric dual-wavelength and lifetime-based photoluminescent oxygen sensing. They were efficiently taken up by cultured murine alveolar macrophages, yielding a characteristic and reversible change in ratiometric response with decreasing oxygen concentration. This correlated with the cellular hypoxic status verified by analysis of hypoxia inducible factor-1α (HIF-1α) accumulation. In addition, the surface of PS-NPs was functionalized with polyethylene glycol (PEG) and the monoclonal antibody herceptin, and their binding to HER2/neu-overexpressing tumor cells was confirmed in vitro. First experiments with tumor-bearing mouse revealed a distinctive ratiometric response within the tumor upon hypoxic condition induced by animal sacrifice. These results demonstrate the potential of these referenced NIR nanosensors for in vitro and in vivo imaging that present a new generation of optical probes for oncology.     

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.     

Investigation of irradiated graphene oxide/ultra-high-molecular-weight polyethylene nanocomposites by ESR and FTIR spectroscopy

Graphene oxide/ultra-high-molecular-weight polyethylene (GO/UHMWPE) nanocomposite has a potential application for artificial joints. However, free radicals and antioxidative properties of irradiated GO/UHMWPE were not clearly clarified. In this paper, GO/UHMWPE nanocomposites were prepared and irradiated by gamma-irradiation with a dose of 100 kGy. Afterward, test samples were aged in air. Free radicals and molecular structures of test samples were investigated by electron spin resonance (ESR) spectroscopy and Fourier transform infrared (FTIR) spectroscopy, respectively. These studies indicated that irradiation enhanced GO radical concentrations. And GO radicals were stable in air and even could not be quenched after accelerated aging. GO radicals were superimposed on free radicals of irradiated UHMWPE. Although GO showed free radical-scavenging capacity, the influence of GO on free radicals of irradiated UHMWPE was too weak to be observed in ESR spectroscopy. Free radicals concentrations of irradiated GO/UHMWPE nanocomposites were gradually decayed with aging time evolving in air. Observing the oxidation index values of test samples, it was proposed that irradiated GO/UHMWPE might show very weak antioxidative properties.     

Mitochondria‐Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual‐modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria‐targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria‐targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.     

Thin surface layer of plasma treated polyethylene

This paper reports on the effect of argon plasma on the high density polyethylene surface. The aim is to alter the surface in a manner and scale resulting in a stronger metal/polymer valence. The specimens are exposed to the direct current discharge, the irradiation time and power being variables. Electron paramagnetic resonance and X-ray photoelectron spectroscopy (EPR and XPS, respectively) are employed to determine the plasma effect. The surface wettability is studied by goniometry. The plasma treatment leads to radical generation and activation of such agents as oxygen, thus the surface wettability is significantly increased. The evolution of the treated surface in different media is studied. The influence of an increased oxygen concentration and the storage medium on the concentration gradient within the surface monolayers is proved. The EPR data show a gradual and very slow decrease in the number of radicals present on the treated surface after 2000 h. Also evidence is given for partial dissolution of the treated surface in water. __________ Translated from Problemy Prochnosti, No. 1, pp. 97–100, January–February, 2008.     

Corannulene‐Incorporated AIE Nanodots with Highly Suppressed Nonradiative Decay for Boosted Cancer Phototheranostics In Vivo

Fluorescent nanoparticles (NPs) based on luminogens with aggregation‐induced emission characteristic (AIEgens), namely AIE dots, have received wide attention because of their antiquenching attitude in emission and reactive oxygen species (ROS) generation when aggregated. However, few reports are available on how to control and optimize their fluorescence and ROS generation ability. Herein, it is reported that enhancing the intraparticle confined microenvironment is an effective approach to advanced AIE dots, permitting boosted cancer phototheranostics in vivo. Formulation of a “rotor‐rich” and inherently charged near‐infrared (NIR) AIEgen with 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000] and corannulene‐decorated PEG affords DSPE‐AIE dots and Cor‐AIE dots, respectively. Compared to DSPE‐AIE dots, Cor‐AIE dots show 4.0‐fold amplified fluorescence quantum yield and 5.4‐fold enhanced ROS production, because corannulene provides intraparticle rigidity and strong interactions with the AIEgen to restrict the intramolecular rotation of AIEgen to strongly suppress the nonradiative decay and significantly facilitate the fluorescence pathway and intersystem crossing. Thus, it tremendously promotes phototheranostic efficacies in terms of NIR image‐guided cancer surgery and photodynamic therapy using a peritoneal carcinomatosis‐bearing mouse model. Collectively, it not only provides a novel strategy to advanced AIE dots for cancer phototheranostics, but also brings new insights into the design of superior fluorescent NPs for biomedical applications.     

A novel photothermally controlled multifunctional scaffold for clinical treatment of osteosarcoma and tissue regeneration

After an osteosarcoma excision, recurrence, large bone defects, and soft tissue injury are significant challenges for clinicians. Conventional treatment by implanting bone replacement materials can induce bone regeneration after surgery, but this does not prevent bleeding, promote soft tissue repair, or help destroy the residual tumor cells. We attempted to develop a new multifunctional scaffold, with the clinical goals of facilitating tumor cell death through thermal ablation and promoting osteogenesis. Accordingly, we first investigated the effect of nano-hydroxyapatite/graphene oxide (nHA/GO) composite particles with different proportions on human osteosarcoma cells (HOS), pre-osteoblastic MC3T3-E1 cells, and human bone marrow mesenchymal stem cells (hBMSC) with or without 808-nm near-infrared (NIR) light irradiation. Next, we fabricated a novel temperature-controlled multifunctional nano-hydroxyapatite/graphene oxide/chitosan (nHA/GO/CS) scaffold, which can effectively kill human osteosarcoma cells under 808-nm NIR irradiation by reaching a temperature of 48 °C and further promote osteogenesis of hBMSC at 42 ± 0.5 °C in coordination with nHA. This scaffold demonstrates the best post-operative bone volume/tissue volume (BV/TV) ratio performance (20.36%) 8 weeks after scaffold implantation in the cranial defects of rats. Further exploration has revealed that NIR irradiation may promote the osteogenesis of hBMSC with the addition of nHA by enhancing the BMP2/Smad signaling pathway. Further, this scaffold has a good hemostatic effect and facilitates soft tissue repair under irradiation. This novel photothermally controlled multifunctional scaffold, which not only kills human osteosarcoma cells but also facilitates tissue regeneration, is a promising clinical tool for treating tissue injuries from an osteosarcoma resection.     

单壁碳纳米管的光解法功能化及其对分散性能的影响(英文)

将单壁碳纳米管分散到溶有光引发剂2-羟基-2-甲基-1-苯基-1-丙醇的四氢呋喃溶液中,在紫外光辐照下,光引发剂裂解生成2-羟基异丙基自由基。通过自由基的偶合反应,2-羟基异丙基自由基偶合到碳纳米管表面。用UV-Vis光谱、FTIR、拉曼光谱、TGA-MS及HRTEM等表征方法,证实在单壁碳纳米管表面引入了羟基。UV-Vis光谱上范霍夫吸收峰的消失表明碳纳米管表面被功能化。羟基化的SWCNTs样品在FTIR光谱中出现的3420cm-1(O—H键)、2930和2859cm-1(烷基C—H键)峰进一步证实了碳纳米管的功能化。拉曼光谱显示,随着SWCNTs的功能化,其切向模式吸收带与杂碳原子吸收带的相对比值(IG/ID)下降。TGA-MS的m/z59峰(400℃)揭示了SWCNTs上存在着异丙醇基团。HRTEM和溶解数据表明,光解改性有助于碳纳米管管束间缠结的解开,进而提高了其在有机溶剂中的溶解性,并且在一定程度上保持了碳纳米管的结构。     

Ultrastable Near‐Infrared Conjugated‐Polymer Nanoparticles for Dually Photoactive Tumor Inhibition

It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low‐bandgap donor–acceptor (D–A)‐type conjugated‐polymer nanoparticles (CP‐NPs) are developed to afford a highly efficient singlet‐to‐triplet transition and photothermal conversion for near‐infrared (NIR) light‐induced photodynamic (PDT)/photothermal (PTT) treatment. CP‐NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP‐NPs undergo singlet‐to‐triplet intersystem crossing through charge transfer in the excited D–A system and simultaneous nonradiative decay from the electron‐deficient electron acceptor isoindigo derivative under single‐wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP‐NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light‐triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP‐NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof‐of‐concept design of D–A‐type conjugated‐polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.     

Fewer Defects in the Surface Slows the Hydrolysis Rate,Decreases the ROS Generation Potential,and Improves the Non‐ROS Antimicrobial Activity of MgO

Magnesium oxide (MgO) is recognised as exhibiting a contact‐based antibacterial activity. However, a comprehensive study of the impact of atomic‐scale surface features on MgO's antibacterial activity is lacking. In this study, the nature and abundance of the native surface defects on different MgO powders are thoroughly investigated. Their impacts on the hydrolysis kinetics, antibacterial activity against Escherichia coli (ATCC 47076), Staphylococcus epidermidis and Pseudomonas aeruginosa and the reactive oxygen species (ROS) generation potential are determined and explained. It is shown that a reduction in the abundance of low‐coordinated oxygen atoms on the surface of the MgO improves its resistance to both hydrolysis and antibacterial activity. The ROS generation potential, determined in‐situ using a fluorescence microplate assay and electron paramagnetic resonance spectroscopy, is not an inherent property of the studied MgO, rather it is a side product of hydrolysis (only for the most highly defected MgO particles) and/or a consequence of the MgO/bacteria interaction. The evaluation of the mutual correlations of the hydrolysis, the antibacterial activity and the ROS generation, with their origin in the surface defects' peculiarities, led to the conclusion that the acid/base reaction between the MgO surface and the bacterial wall contributes considerably to the MgO's antibacterial activity.     

Synergistic Enzyme-Mimetic Catalysis-Based Non-Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation (Small 42/2023)

Non-invasive cancer treatment strategies that enable local non-thermal ablation, hypoxia relief, and reactive oxygen species (ROS) production to achieve transiently destroying tumor tissue and long-term killing tumor cells would greatly facilitate their clinical applications. However, continuously generating oxygen cavitation nuclei, reducing the transient cavitation sound intensity threshold, relieving hypoxia, and improving its controllability in the ablation area still remains a significant challenge. Here, in this work, an Mn-coordinated polyphthalocyanine sonocavitation agent (Mn-SCA) with large d-π-conjugated network and atomic Mn-N sites is identified for the non-thermal sonocavitation and sonodynamic therapy in the liver cancer ablation. In the tumor microenvironment, the catalytical generation of oxygen assists cavitation formation and generates microjets to ablate liver cancer tissue and relieve hypoxia, this work reports for the first time to utilize the enzymatic properties of Mn-SCA to lower the cavitation threshold in situ. Moreover, under pHIFU irradiation, high reactive oxygen species (ROS) production can be achieved. The two merits in liver cancer ablation are demonstrated by cell destruction and high tumor inhibition efficiency. This work will help deepen the understanding of cavitation ablation and the sonodynamic mechanisms related to the nanostructures and guide the design of sonocavitation agents with high ROS production for solid tumor ablation.     

Electrochemical Monitoring of Paclitaxel‐Induced ROS Release from Mitochondria inside Single Cells

Mitochondria are believed to be the major source of intracellular reactive oxygen species (ROS). However, in situ, real‐time and quantitative monitoring of ROS release from mitochondria that are present in their cytosolic environment remains a great challenge. In this work, a platinized SiC@C nanowire electrode is placed into a single cell for in situ detection of ROS signals from intracellular mitochondria, and antineoplastic agent (paclitaxel) induced ROS production is successfully recorded. Further investigations indicate that complex IV (cytochrome c oxidase, COX) is the principal site for ROS generation, and significantly more ROS are generated from mitochondria in cancer cells than that from normal cells. This work provides an effective approach to directly monitor intracellular mitochondria by nanowire electrodes, and consequently obtains important physiological evidence on antineoplastic agent‐induced ROS generation, which will be of great benefit for better understanding of chemotherapy at subcellular levels.     

Efficacy Dependence of Photodynamic Therapy Mediated by Upconversion Nanoparticles: Subcellular Positioning and Irradiation Productivity

Singlet oxygen (¹O₂), as an important kind of reactive oxygen species (ROS) and main therapeutic agent in photodynamic therapy (PDT), only have a half‐life of 40 ns and an effective radius of 20 nm, which cause significant obstacles for improving PDT efficacy. In this work, novel upconversion nanoparticle (UCN)‐based nanoplatforms are developed with a minimized distance between UCNs and a photosensitizer, protoporphyrin IX (PpIX), and a controllable payload of PpIX, to enhance and control ROS production. The ability of the nanoplatform to target different subcellular organelles such as cell membrane and mitochondria is demonstrated via surface modification of the nanoplatform with different targeting ligands. The results show that the mitochondria‐targeting nanoplatforms result in significantly increased capability of both tumor cell killing and inhibition of tumor growth. Subcellular targeting of nanoparticles leads to the death of cancer cells in different manners. However, the efficiency of ROS generation almost have no influence on the tumor cell viability during the period of evaluation. These findings suggest that specific subcellular targeting of the nanoplatforms enhances the PDT efficacy more effectively than the increase of ROS production, and may shed light on future novel designs of effective and controllable PDT nanoplatforms.     

Antimicrobial activity and cellular toxicity of nanoparticle-polymyxin B conjugates

We investigate the antimicrobial activity and cytotoxicity to mammalian cells of conjugates of the peptide antibiotic polymyxin B (PMB) to Au nanoparticles and CdTe quantum dots. Au nanoparticles fully covered with PMB are identical in antimicrobial activity to the free drug alone, whereas partially-conjugated Au particles show decreased effectiveness in proportion to the concentration of Au. CdTe-PMB conjugates are more toxic to Escherichia coli than PMB alone, resulting in a flattening of the steep PMB dose-response curve. The effect is most pronounced at low concentrations of PMB, with a greater effect on the concentration required to reduce growth by half (IC50) than on the concentration needed to inhibit all growth (minimum inhibitory concentration, MIC). The Gram positive organism Staphylococcus aureus is resistant to both PMB and CdTe, showing minimal increased sensitivity when the two are conjugated. Measurement of reactive oxygen species (ROS) generation shows a significant reduction in photo-generated hydroxyl and superoxide radicals with CdTe-PMB as compared with bare CdTe. There is a corresponding reduction in toxicity of QD-PMB versus bare CdTe to mammalian cells, with nearly 100% survival in fibroblasts exposed to bactericidal concentrations of QD-PMB. The situation in bacteria is more complex: photoexcitation of the CdTe particles plays a small role in IC50 but has a significant effect on the MIC, suggesting that at least two different mechanisms are responsible for the antimicrobial action seen. These results show that it is possible to create antimicrobial agents using concentrations of CdTe quantum dots that do not harm mammalian cells.