Raviraj Vankayala

Designing Multi-Branched Gold Nanoechinus for NIR Light Activated Dual Modal Photodynamic and Photothermal Therapy in the Second Biological Window

Gold nanoechinus can sensitize the formation of singlet oxygen in the first and the second near-infra red (NIR) biological windows and exert in vivo dual modal photodynamic and photothermal therapeutic effects (PDT and PTT) to destruct the tumors completely. This is the first literature example of the destruction of tumors in NIR window II induced by dual modal nanomaterial-mediated photodynamic and photothermal therapy (NmPDT & NmPTT).

Metal Nanoparticles Sensitize the Formation of Singlet Oxygen

Singlet oxygen (O2) is known to play an indispensible role in the photodynamic therapy (PDT) treatment of cancer, and is an important oxidant for hydroperoxidation of olefins in organic synthesis. Singlet O2 is conventionally formed by sensitization by organic photosensitizers, such as Rose Bengal, silicon phthalocyanine, etc. These organic or organometallic dyes are, however, prone to photoinduced degradation and enzymatic degradation, which becomes problematic in PDT treatments, and reduces the efficiency of the generation of singlet O2. [5,8] It is, therefore, important to search for photosensitizers with highly efficient singlet O2 generation and large absorption coefficients that are photochemically more stable and less prone to enzymatic degradation. Previously, it was reported that the yield of singlet oxygen production by a photosensitizer, namely, Rose Bengal, was enhanced by a silver island film through the metal-enhanced absorption of photosensitizer. It was also reported that a gold nanodisk could enhance the phosphorescence decay rate of singlet oxygen, leading to a larger characteristic phosphorescence emission band of singlet oxygen at 1270 nm. In another two studies, it was observed that the quantum yield of singlet O2 formation generated by phthalocyanine photosensitizers can be enhanced by the presence of gold nanoparticles. Herein we report an unprecedented observation that singlet oxygen can be formed through direct sensitization by metal nanoparticles (M NPs, M=Ag, Pt, and Au) without the presence of any organic photosensitizers. Unambiguous experimental evidence includes direct observation of singlet oxygen emission at roughly 1268 nm, hydroperoxidation of cyclohexene, green fluorescence from a selective singlet oxygen fluorescent sensor, namely, Singlet Oxygen Sensor Green (SOSG, Molecular Probe), and quenching of singlet oxygen phosphorescence by sodium azide. As shown in Figure 1, photoexcitation of M NPs at the surface plasmon resonance absorption bands of Ag (d= 55, 42 nm), Pt (10 nm), and Au (22 nm) in D2O results in characteristic singlet oxygen emission at 1264 and 1268 nm, respectively. Control experiments show that in the absence of metal nanoparticles, photoexcitation of poly(vinyl pyrrolidone (PVP) in D2O using either 254 or 508 nm light did not result in any detectable singlet O2 emission signal (see the

First Demonstration of Gold Nanorods‐Mediated Photodynamic Therapeutic Destruction of Tumors via Near Infra‐Red Light Activation

Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1-48 W/cm²) irradiation, leading to hyperthermia-induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs-mediated PTT and organic photosensitizers-mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (¹O₂) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm²) light excitation. By changing the NIR light excitation wavelengths, Au NRs-mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti-cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon-induced fluorescence to illustrate their in vivo locations/distribution.

Photosensitization of Singlet Oxygen and In Vivo Photodynamic Therapeutic Effects Mediated by PEGylated W18O49 Nanowires

Upon excitation with near-infrared light (980 nm), PEGylated W18 O49 nanowires can sensitize the formation of singlet oxygen and thus reactive oxygen species (ROS). The resulting photodynamic therapy (PDT) effect can cause the destruction of tumors in the absence of organic photosensitizers. PEG=poly(ethylene glycol), PTT=photothermal therapy.

Morphology dependent photosensitization and formation of singlet oxygen (1Δg) by gold and silver nanoparticles and its application in cancer treatment

Singlet oxygen is a very important reactive oxygen species (ROS) involved in peroxidation of olefins and polymers, as well as in clinical photodynamic therapy treatments of tumors. Previously, it was reported that singlet oxygen can be formed via sensitization by spherical metal nanoparticles upon photo-excitation of the surface plasmon resonance (SPR) bands. In this paper, we report that sensitization and formation of singlet O2 is strongly dependent on the morphologies of gold and silver nanostructures. For example, singlet O2 can be generated via photo-irradiation and sensitization of silver decahedrons and silver triangular nanoplates, but not by silver nanocubes and gold decahedrons. The sensitization patterns of silver and gold nanoparticles are the reverse of each other. In the case of gold nanorods, singlet O2 can be generated via photo-excitation at the longitudinal SPR band, but not by excitation at the transverse SPR band. The controlling factors for such a morphology dependent singlet O2 sensitization will be discussed. Furthermore, we also demonstrate in vitro morphology dependent sensitization behaviour of silver nanoparticles in the photodynamic cancer treatment. Our results indicate that metal nanoparticles with certain morphologies are potentially very promising dual functional nanomaterials with capabilities of simultaneously serving as near infrared (NIR) activatable photodynamic therapy and photothermal therapy reagents for cancer treatments.

Bioinspired reduced graphene oxide nanosheets using Terminalia chebula seeds extract.

A green one step facile synthesis of graphene nanosheets by Terminalia chebula (T. chebula) extract mediated reduction of graphite oxide (GO) is reported in this work. This method avoids the use of harmful toxic reducing agents. The comparative results of various characterizations of GO and T. chebula reduced graphene oxide (TCG) provide a strong indication of the exclusion of oxygen containing groups from graphene oxide and successive stabilization of the formed reduced graphene oxide (RGO). The functionalization of reduced graphene oxide with the oxidized polyphenols causes their stability by preventing the aggregation. We also have proposed how the oxidized polyphenols are accountable for the stabilization of the formed graphene sheets.

Complete destruction of deep-tissue buried tumors via combination of gene silencing and gold nanoechinus-mediated photodynamic therapy

Cancer is one of the major diseases leading to human deaths. Complete destruction of deep tissue-buried tumors using non-invasive therapies is a grand challenge in clinical cancer treatments. Many therapeutic modalities were developed to tackle this problem, but only partial tumor suppression or delay growths were usually achieved. In this study, we report for the first time that complete destruction of deep tissue-buried tumors can be achieved by combination of gold nanoechinus (Au NEs)-mediated photodynamic therapy (PDT) and gene silencing under ultra-low doses of near infra-red (NIR) light irradiation (915 nm, 340 mW/cm(2); 1064 nm, 420 mW/cm(2)) in the first and second biological windows. The average lifespan of the mice treated by the above combined therapy is beyond 40 days, which are ∼ 2.6 times longer than that (15 days) observed from the anticancer drug doxorubicin-treated group. The current study points out a new direction for the therapeutic design to treat deeply seated tumors in future cancer treatments.

Biocompatibility of Polymer Grafted Core/Shell Iron/Carbon Nanoparticles

For biomedical applications, emerging nanostructures requires stringent evaluations for their biocompatibility. Core/shell iron/carbon nanoparticles (Fe@CNPs) are nanomaterials that have potential applications in magnetic resonance imaging (MRI), magnetic hyperthermia and drug delivery. However, their interactions with biological systems are totally unknown. To evaluate their potential cellular perturbations and explore the relationships between their biocompatibility and surface chemistry, we synthesized polymer grafted Fe@CNPs with diverse chemistry modifications on surface and investigated their dynamic cellular responses, cell uptake, oxidative stress and their effects on cell apoptosis and cell cycle. The results show that biocompatibility of Fe@CNPs is both surface chemistry dependent and cell type specific. Except for the carboxyl modified Fe@CNPs, all other Fe@CNPs present low toxicity and can be used for further functionalization and in a wide range of biomedical applications.

Casein mediated green synthesis and decoration of reduced graphene oxide

This research is mainly focusing on one-step biosynthesis of graphene from graphene oxide and its stabilization using naturally occurring milk protein, casein. The synthesis of casein reduced graphene oxide (CRGO) was completed within 7h under reflux at 90°C with the formation of few layered fine graphene nanosheets. UV-Vis, XRD, XPS analysis data revealed the reduction process of the graphene oxide. Results of FT-IR, HPLC and TEM analysis have shown that the ensuing material consists of graphene decorated with casein molecules. Aspartic acid and glutamic acid residue present in casein molecules are responsible for the reduction of graphene oxide.

Preparation, cytotoxicity and in vivo bioimaging of highly luminescent water-soluble silicon quantum dots.

Designing various inorganic nanomaterials that are cost effective, water soluble, optically photostable, highly fluorescent and biocompatible for bioimaging applications is a challenging task. Similar to semiconducting quantum dots (QDs), silicon QDs are another alternative and are highly fluorescent, but non-water soluble. Several surface modification strategies were adopted to make them water soluble. However, the photoluminescence of Si QDs was seriously quenched in the aqueous environment. In this report, highly luminescent, water-dispersible, blue- and green-emitting Si QDs were prepared with good photostability. In vitro studies in monocytes reveal that Si QDs exhibit good biocompatibility and excellent distribution throughout the cytoplasm region, along with the significant fraction translocated into the nucleus. The in vivo zebrafish studies also reveal that Si QDs can be evenly distributed in the yolk-sac region. Overall, our results demonstrate the applicability of water-soluble and highly fluorescent Si QDs as excellent in vitro and in vivo bioimaging probes.