Near-infrared Ⅱ Plasmonic Multifunctional Biomedical Materials

Cancer is one of the leading causes of human deaths worldwide.It has been estimated that there will be 29.5 million new cancer cases by 2040.Surgery,chemotherapy and radiotherapy are the most commonly used methods for clinical treatment of cancer.These methods can effectively treat primary tumor but suffers from low treatment efficiency and high risk of cancer recurrence.Multimodal phototheranostics combining diagnostics and therapy in a single entity exploits external light stimuli for simultaneous diagnostics and in situ therapy of cancer.It presents great advantages including light controllability,high spatial resolution,high accurateness,non-invasiveness,rapidness and real-time.These prominent features are conductive to the therapeutic treatment with reduced side-effects.However,the clinical application of phototheranostics is restricted by the limited light penetration depth,the lacking of multifunctionality and low targeting efficiency.Plasmonic materials exhibit absorption coefficients several orders-of-magnitude larger than traditional optofunctional materials,and feature excellent multifunctionalities including surface-enhanced Raman scattering（SERS）detection,photothermal（PT）imaging,photoacoustic（PA）imaging,and computed tomography（CT）imaging for diagnostic applications,and photothermal therapy（PTT）,chemodynamic therapy（CDT）and（or）drug carriers for therapeutic applications.Thus,plasmonic materials hold great promises for phototheranostics of cancer.As is well-known,biological tissues have less optical absorption and scattering,and negligible autofluorescence in the near-infrared Ⅱ（NIR-Ⅱ,1000-1700 nm）biowindow,which results in a high tissue penetration depth of up to several centimeters.In addition,the maximum permissible laser power density of NIR-Ⅱ light is as high as1 W/cm²,significantly higher than the visible（400-700 nm）and NIR-I（700-900 nm）light.Taking all these into accounts,this thesis deals with NIR-Ⅱ plasmonic materials for phototheranostic applications,and the following accomplishments are summarized:（1）A Se template-mediated two step method is developed for synthesis of concentric Au@Cu_2-xSe core/shell nanocrystals（GCS NCs）,which reveals the effective tailoring of Cu_2-xSe shell and the resulting tuning the NIR-Ⅱ plasmonic/photothermal properties by varying the Se O₂concentration.It is demonstrated that effective·OH production can be obtained by Fenton-like reaction and plasmonic hole-induced photocatalytic reaction in concentric GCS NCs,which could be utilized for·OH-mediated CDT and PCT.The excellent NIR-Ⅱ photothermal performance can be used for cancer photothermal ablation.We demonstrate that concentric GCS NCs serve as an excellent phototheranostic platform for PA/PT/CT multi-modal imaging-guided CDT/PCT/PTT combination therapy triggered by a single NIR-Ⅱ excitation wavelength.（2）It is found that GCS nanocrescents can be synthesized using the Setemplate-mediatedtwo-stepmethodwith hexadecyltrimethylammonium chloride（CTAC）as the capping ligand.The offset degree and Cu_2-xSe size in the GCS nanocrescents can be tuned by varying the Se O₂concentration,consequently tuning the NIR-Ⅱ NIR-Ⅱ plasmonic properties.The electron transfer from the Au to Cu_2-xSe domains is verified by transient absorption and extinction spectral measurements,and the Cu_2-xSe-dependent bleaching amplitude and carrier dynamics of the Au-and Cu_2-xSe-associated plasmons are revealed owing to variations of the carrier-photon and photon-phonon relaxation processes.（3）The regioselective growth of Cu_2-xSe on the surface of gold nanorods（GNRs）is discovered by the Se template-mediated two-step method using different capping ligands.The lateral one-and two-side depositions,conformal core-shell coating and island growth of Cu_2-xSe on theGNRsareachievedusingCTAC,cationic hexadecyltrimethylammonium bromide（CTAB）,neutral poly（vinylpyrrolidone）（PVP）and anionic poly（sodium 4-styrenesulfonate）（PSS）,and cationic poly（diallyldimethyl ammonium chloride）（PDDA）,respectively.The NIR-Ⅱ plasmonic properties（i.e.,position,amplitude）can be controlled by the initial Se O₂concentration.We demonstrate that these GNR@Cu_2-xSe heterostructures possess excellent NIR-I and NIR-Ⅱ photothermal conversion efficiency（58-85%）,which can serve as superior photothermal agents for in vivo photothermal tumor ablation.（4）It is revealed that the structural symmetry of GCS NCs significantly affects the plasmonic/photothermal properties and Fenton-like effects.Results show that Janus-GCS NCs exhibit much higher NIR-Ⅱ plasmon absorption cross-section and NIR-Ⅱ photothermal conversion efficiency in comparison with the concentric and non-concentric GCS core/shell heterostructures.In addition,more efficient·OH production and GSH depletion are observed in Janus-GCS NCs.These prominent features endow Janus-GCS NCs with excellent performance for PA/CT imaging-guided CDT/PTT combination therapy of cancer.（5）A novel NIR-Ⅱ plasmonic Au@Au-Ag dot-in-cubic nanoframes（DCFs）with small size is developed for in vivo NIR-Ⅱ SERS detection and PA imaging of microtumors.The developed Au@Au-Ag DCFs comprise a spherical Au core and a Au-Ag alloy cubic shell with a wall hole on each side face.The edge length and wall hole size can be controllably tailored by simply varying silver nitrate and chloroauric acid concentrations,consequently achieving spectral tunability in the range of700-1400 nm for Au@Au-Ag DCFs.In vivo experiments demonstrate the successful detection of microtumors in animals using NIR-Ⅱ SERS detection and PA imaging.The developed Au@Au-Ag DCFs hold great promises for real-time intraoperative elimination of microtumors to improve surgical resection of tumors.Overall,this thesis greatly advances the synthesis of NIR-Ⅱ plasmonic materials and their applications for diagnostic optical imaging and multi-modal phototherapy,unambiguously demonstrating the great promises of the developed NIR-Ⅱ plasmonic materials for multimodal phototheranostics.