Seite - 126 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Liuet al. AuNS forcancer imagingand therapy FIGURE2 |TPL imagesofDAPI- (nucleus;blue)andCD31 (blood vessel; red)-stainedcryosectionedspecimens fromperfusedbrain excised48-hrafter injection (5pmole;80nm)ofneutralPEG-AuNS (A–C)andpositively-chargedTAT-AuNS(D–F), and injection (1pmole; 50nm)ofangiopep2-AuNS(G–I). Large-area tile imagesshowing distributionofPEG-AuNS (A), TAT-AuNS (D), Angiopep2-AuNS (G) preferentially in thebrain tumor thannormalbrain. T, tumor.N,normal. ChargedTAT-AuNSaccumulatedgreater in the liver hence lower intratumoral accumulation.Smaller angiopep2-AuNSwasmorewidespread in the tumor. Scalebar: 100µm(Yuanetal., 2014). beenused toperformPTTwitha femtosecondTi:Sapphire laser (810nm, 1.5W/cm2 for 5min) for SK-BR-3 breast cancer cells. The treatment group shows amajority of cells diedwhile there was little cellular death in the control group (Skrabalak et al., 2007).Gold nanorodswithT790dye embedded in a silica shell were developed to perform PDT and the improved treatment efficiencyhasbeendemonstratedwithHepG2cancercells (Zhao et al., 2014b). In particular, the star-shape geometry of AuNS generates a strong tip-enhanced plasmonic effect that greatly increases the photothermal transduction efficiency especially in the NIR tissue optical window. Successful photothermolysis has been demonstrated in both single photon and two photon settings (Yuan et al., 2012a,c). An ultralow irradiance of 0.2 W/cm2 (at using 850nm pulsed laser), which was below the maximal permissible exposure of skin, was reported. A recent study demonstrated that AuNS exhibit higher photothermal transduction efficiency than goldnanoshells (90–94% forAuNS compared to 61% for gold nanoshells). In vivo experiment also revealed a successful photothermal ablation of aggressive sarcoma tumor in mouse after AuNS systemical injection through tail vein (Liu et al., 2015a). In addition, we also loaded Protoporphyrin IX onto silica-coated AuNS for PDT showing specific cytotoxic effect onlyon theUVexposed region (Figure1C) (Fales et al., 2013). These results demonstrated that AuNShavegreatpotential forPDTandphotothermal therapy in futurepreclinical cancer treatmentstudies. ConclusionandFuturePerspective The AuNS synthesized with the surfactant-free method provide a novel nanoplatform for cancer nanotheranostics. Themultifunctional AuNS nanoprobes can be used for future pre-treatment cancer diagnostics with PET, MRI, and CT scan, intraoperative imaging with TPL, PAT, and SERS, and image-guided therapy with PDT and PTT. The plasmonic AuNS is a promising theranostic nanoplatform since they have combined capabilities for diagnostics with various imaging modalities from whole-body to subcellular level, therapeutics with phototherapy and drug delivery, and surface functionalization versatility for cancer targeting. Compared to other gold plasmonic nanoplatforms, the AuNS nanoprobes have unique advantages of tip-enhanced plasmonics, high TPL cross-section, and excellent photon-to-heat conversion efficiency, toxic surfactant-free synthesis. Further studies on relationship between AuNS properties including particle size and surface charge, and their biodistribution are still required to improve nanoprobe uptake in tumor for better biomedical applications. With promising findings from previous studies, AuNS demonstrate great potential for translational medicine studiesasacombinednanoplatformforbothcancer imagingand therapy. Acknowledgments Thiswork is partly supported by theDuke Faculty Exploratory Project.YangLiu is supportedby theKathleenZielek fellowship from the Chemistry Department of Duke University. The authors also would like to acknowledge theDefense Advanced Research Projects Agency (HR0011-13-2-0003). The content of the information in this paper does not necessarily reflect the position or the policy of the government, and no official endorsementshouldbe inferred. Frontiers inChemistry |www.frontiersin.org August2015 |Volume3 |Article51 126|