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Jianfeng Guo,1 Kamil Rahme,2–4 Yan He,1 Lin-Lin Li,5 Justin D Holmes,3,4 Caitriona M O’Driscoll6 1School of Pharmaceutical Sciences, Jilin University, Changchun, China; 2Department of Sciences, Faculty of Natural and Applied Science, Notre Dame University (Louaize), Zouk Mosbeh, Lebanon; 3Department of Chemistry, Tyndall National Institute, University College Cork, Cork, 4AMBER@CRANN, Trinity College Dublin, Dublin, Ireland; 5The First Hospital of Jilin University, Changchun, China; 6Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland Abstract: Development of multifunctional nanomaterials, one of the most interesting and advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer diagnosis and treatment. Gold nanoparticles (AuNPs) are now being widely utilized in bioimaging and phototherapy due to their tunable and highly sensitive optical and electronic properties (the surface plasmon resonance). As a new concept, termed “theranostics,” multifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic and phototherapeutic applications such as structure, shape, optics, and surface chemistry are described. Barriers for translational development of theranostic AuNPs and recent advances in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy are discussed. Keywords: multifunctional gold nanoparticles, cancer bioimaging, cancer photothermal and photodynamic therapy

Abstract Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl 4 , FeCl 2), whereas Na 2 SeO 3 supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al. Graphical Abstract The cancer cells' unique microenvironment provides an opportunity for the biosynthesis of metallic nanoscale particles of <10 nm size. These gold and iron nanoclusters were biosynthesized in neoplastic tissue and then loaded on the exosomes that were automatically generated by the cancer cells and disseminated into the blood and surrounding environment. These gold and iron nanoclusters loaded exosomes were isolated and then characterized by TEM and fluorescence bioimaging for potential cancer diagnosis, especially the reoccurrence of cancer after tumor ablation via radio or chemotherapies. Unlabelled Image [ABSTRACT FROM AUTHOR]

Semiconductor quantum dots (QDs) are one of the most interesting photoluminescent nanomaterials with very promising applications in cancer nanomedicine. In this work, ZnS fluorescent quantum dots (ZnS-QDs) were synthesized and stabilized by carboxymethylcellulose (CMC) as a pH-sensitive biopolymer using a facile one-step green aqueous colloidal process at distinct pH conditions (acidic, neutral and alkaline) and chemical proportions of precursors (Zn2+, S2−). The optical properties of these nanoconjugates (ZnS@CMC) were characterized by UV–visible and photoluminescence spectroscopy. The morphological features and physicochemical properties were evaluated by TEM, FTIR spectroscopy, zeta potential, and dynamic light scattering (DLS) analyses. The cytocompatibility in vitro of ZnS@CMC was assessed by MTT assay using normal and malignant glioma cells. The UV–Vis results indicated that ZnS-QDs were effectively produced with different bandgap energies (from 4.5 to 3.8 eV) blue-shifted from bulk (E bulk = 3.61 eV), and sizes (typically from 3.3 to 4.5 nm), dependent on the pH and concentration ratio of precursors during the synthesis. Analogously, the changes of synthesis parameters significantly altered the photoluminescence emission energies and intensities within the visible range of spectra (PL maxima from λ = 400–430 nm, at pH = 3.5, [Zn:S] ratio = 1:2). The cell viability results in vitro (>90%) demonstrated no cytotoxicity of ZnS@CMC nanohybrids towards both cell types. Importantly, these ZnS@CMC nanoconjugates behaved as active fluorescent nanoprobes for bioimaging malignant glioma cells proving the high potential for applications in cancer nanomedicine. Image 1004 • Facile green synthesis of ZnS quantum dot-carboxymethylcellulose nanoconjugates. (79). • CMC pH-sensitive ligand tailored nucleation/growth processes of ZnS nanocrystals. (80). • Colloidal process parameters regulated the optical properties of ZnS@CMC nanohybrids. (84). • ZnS@CMC colloids behaved as active photoluminescent biological nanoprobes. (73). • Fluorescent nanoconjugates were effective for bioimaging brain cancer cells in vitro. (84). [ABSTRACT FROM AUTHOR]

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl 4 , FeCl 2 ), whereas Na 2 SeO 3 supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Anti-HER2 antibody conjugated with quantum dots (anti-HER2ab-QDs) is a very recent fluorescent nanoprobe for HER2+ve breast cancer imaging. In this study we investigated in-vivo toxicity of anti-HER2ab conjugated CdSe/ZnS QDs in Wistar rats. For toxicity evaluation of injected QDs sample, body weight, organ coefficient, complete blood count (CBC), biochemistry panel assay (AST, ALT, ALP, and GGTP), comet assay, reactive oxygen species, histology, and apoptosis were determined. Wistar rat (8-10 weeks old) were randomly divided into 4 treatment groups (n = 6). CBC and biochemistry panel assay showed nonsignificant changes in the anti-HER2ab-QDs treated group but these changes were significant (P < 0.05) in QDs treated group. No tissue damage, inflammation, lesions, and QDs deposition were found in histology and TEM images of the anti-HER2ab-QDs treated group. Apoptosis in liver and kidney was not found in the anti-HER2ab-QDs treated group. Animals treated with nonconjugated QDs showed comet formation and apoptosis. Cadmium deposition was confirmed in the QDs treated group compared with the anti-HER2ab-QDs treated group. The QDs concentration (500 nM) used for this study is suitable for in-vivo imaging. The combine data of this study support the biocompatibility of anti-HER2ab-QDs for breast cancer imaging, suggesting that the antibody coating assists in controlling any possible adverse effect of quantum dots.