Recent advances in near infrared light responsive multi-functional nanostructures for phototheranostic applications.

Light-based theranostics have become indispensable tools in the field of cancer nanomedicine. Specifically, near infrared (NIR) light mediated imaging and therapy of deeply seated tumors using a single multi-functional nanoplatform have gained significant attention. To this end, several multi-functional nanomaterials have been utilized to tackle cancer and thereby achieve significant outcomes. The present review mainly focuses on the recent advances in the development of NIR light activatable multi-functional materials such as small molecules, quantum dots, and metallic nanostructures for the diagnosis and treatment of deeply seated tumors. The need for improved disease detection and enhanced treatment options, together with realistic considerations for clinically translatable nanomaterials will be the key driving factors for theranostic agent research in the near future. NIR-light mediated cancer imaging and therapeutic approaches offer several advantages in terms of minimal invasiveness, deeper tissue penetration, spatiotemporal resolution, and molecular specificities. Herein, we have reviewed the recent developments in NIR light responsive multi-functional nanostructures for phototheranostic applications in cancer therapy.

Recent Advances of Polyaniline-Based Biomaterials for Phototherapeutic Treatments of Tumors and Bacterial Infections.

Conventional treatments fail to completely eradicate tumor or bacterial infections due to their inherent shortcomings. In recent years, photothermal therapy (PTT) has emerged as an attractive treatment modality that relies on the absorption of photothermal agents (PTAs) at a specific wavelength, thereby transforming the excitation light energy into heat. The advantages of PTT are its high efficacy, specificity, and minimal damage to normal tissues. To this end, various inorganic nanomaterials such as gold nanostructures, carbon nanostructures, and transition metal dichalcogenides have been extensively explored for PTT applications. Subsequently, the focus has shifted to the development of polymeric PTAs, owing to their unique properties such as biodegradability, biocompatibility, non-immunogenicity, and low toxicity when compared to inorganic PTAs. Among various organic PTAs, polyaniline (PANI) is one of the best-known and earliest-reported organic PTAs. Hence, in this review, we cover the recent advances and progress of PANI-based biomaterials for PTT application in tumors and bacterial infections. The future prospects in this exciting area are also addressed.

Preparation, Cytotoxicity, and In Vitro Bioimaging of Water Soluble and Highly Fluorescent Palladium Nanoclusters.

Fluorescent probes offer great potential to identify and treat surgical tumors by clinicians. To this end, several molecular probes were examined as in vitro and in vivo bioimaging probes. However, due to their ultra-low extinction coefficients as well as photobleaching problems, conventional molecular probes limit its practical utility. To address the above mentioned challenges, metal nanoclusters (MNCs) can serve as an excellent alternative with many unique features such as higher molar extinction coefficients/light absorbing capabilities, good photostability and appreciable fluorescence quantum yields. Herein, we reported a green synthesis of water soluble palladium nanoclusters (Pd NCs) and characterized them by using various spectroscopic and microscopic characterization techniques. These nanoclusters showed excellent photophysical properties with the characteristic emission peak centered at 500 nm under 420 nm photoexcitation wavelength. In vitro cytotoxicity studies in human cervical cancer cells (HeLa) cells reveal that Pd NCs exhibited good biocompatibility with an IC50 value of >100 µg/mL and also showed excellent co-localization and distribution throughout the cytoplasm region with a significant fraction translocating into cell nucleus. We foresee that Pd NCs will carry huge potential to serve as a new generation bioimaging nanoprobe owing to its smaller size, minimal cytotoxicity, nucleus translocation capability and good cell labelling properties.

Nano-graphene oxide-mediated In vivo fluorescence imaging and bimodal photodynamic and photothermal destruction of tumors.

Cancer is one of the major life-threatening diseases among human beings. Developing a simple, cost-effective and biocompatible approach to treat cancers using ultra-low doses of light is a grand challenge in clinical cancer treatments. In this study, we report for the first time that nano-sized graphene oxide (GO) exhibits single-photon excitation wavelength dependent photoluminescence in the visible and short near-infrared (NIR) region, suitable for in vivo multi-color fluorescence imaging. We also demonstrate in both in vitro and in vivo experiments to show that nano GO can sensitize the formation of singlet oxygen to exert combined nanomaterial-mediated photodynamic therapeutic (NmPDT) and photothermal therapy (NmPTT) effects on the destruction of B16F0 melanoma tumors in mice using ultra-low doses (∼0.36 W/cm(2)) of NIR (980 nm) light. The average half-life span of the mice treated by the GO-PEG-folate-mediated NmPDT effects is beyond 30 days, which is ∼1.8 times longer than the mice treated with doxorubicin (17 days). Overall, the current study points out a successful example of using GO-PEG-folate nanocomposite as a theranostic nanomedicine to exert simultaneously in vivo fluorescent imaging as well as combined NmPDT and NmPTT effects for clinical 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.

Gold nanoshells-mediated bimodal photodynamic and photothermal cancer treatment using ultra-low doses of near infra-red light.

Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm(2)), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under ultra-low laser doses.

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.

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.

Effects of surface functionality of carbon nanomaterials on short-term cytotoxicity and embryonic development in zebrafish.

Nanomaterials have been widely used in the biomedical field as gene/drug carriers, magnetic resonance imaging (MRI) contrast reagents, photothermal therapy reagents, fluorescent cellular markers, etc. The origins and working mechanisms of cytotoxicities of nanomaterials, however, are not well understood. It is often stated in the literature that a nanomaterial is non-toxic and biocompatible. In this study, we show that the short term cytotoxicity of a nanomaterial is determined by the surface functionality, rather than the core nanomaterial. A so-called "non-toxic and biocompatible" nanomaterial, such as core/shell iron-filled carbon nanoparticles (Fe@CNPs) and nanodiamonds (NDs), can become cytotoxic when a cationic surface functionality, such as imidazolium (IM) and tertiary methyl ammonium ethyl methacrylate (TMAEA) moieties, was grafted onto the surface. To investigate the contributions of surface functionalities and the core nanomaterials on cytotoxicity, two "non-toxic and biocompatible" Fe@CNPs and NDs were surface-modified with different surface functionalities, including anionic COOH, zwitterionic PVP, neutral OH, cationic IM and TMAEA, and investigated for their cytotoxicities in both in vitro cancer cells (HeLa and U-87MG cells) and in vivo embryo development of zebrafish. Among these surface functionalities, cationic IM and TMAEA functionalities of both Fe@CNPs and NDs cause acute cytotoxicity to a similar extent in the in vitro cancer cell experiments, as well as affect severely the embryonic development and survival rates of zebrafish. Other surface functionalities do not show particularly strong cytotoxicities. To obtain information regarding the origins of cytotoxicities, the effects of surface functionalities were also examined on the lactate dehydrogenase (LDH) levels, cellular ROS generation, apoptosis, and changes in lysosomal membrane integrity, mitochondrial membrane potential, the intracellular pH (pHi), and cell cycles. Our results clearly point out that surface functionality, rather than the core nanomaterials, plays a critical role in dictating the short-term cytotoxicities.

Photosensitization of singlet oxygen and in vivo photodynamic therapeutic effects mediated by PEGylated W(18)O(49) 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.