Self-assembled Gold Super-nanoparticles For SERS Imaging Guided Cancer Therapy

Cancer,which possesses an intricate structure and constituents that are distinct from normal tissues,has become one of the major threats to the human health.Recently,multifunctional cancer theranostics nanoplatforms that combined with diagnosis and treatment have attracted widespread attention.Especially,imaging-guided cancer therapeutic strategies are helpful to manage the treatment by monitoring cancer progression.Compared with computed tomography?CT?,magnetic resonance imaging?MRI?,fluorescence?FL?imaging,surface enhanced Raman scattering?SERS?imaging plays an increasingly important role in the diagnosis of cancer due to its high sensitivity and specificity.The primary requirement for the enhancement of SERS signal is the presence of highly populated hot spots on a metallic surface.Therefore,it is necessary to design a stable substrate with high density of hot spots for SERS imaging guided cancer therapy.Conventional cancer therapy methods,such as surgery,radiation therapy,and chemotherapy,suffer from the risk of toxic side effects,incomplete tumor eradication,and therapy resistance.Phototherapy is a promising cancer therapeutic approach that selectively kills cancer cells via light triggered cytotoxicity.Photothermal therapy?PTT?,which converts near-infrared?NIR?light into heat for thermal ablation of cancer cells,is standout from cancer treatment methods owing to its unique advantages including minimal invasiveness,high specificity,effective tumor ablation,and low side effects to normal tissues.As another non-invasive treatment,photodynamic therapy?PDT?is a modality that employs a photosensitizer,an appropriate excitation light,and oxygen?O₂?molecules to generate cytotoxic reactive oxygen species?ROS?and destroy the malignant tumor.However,the generation of ROS depends strongly on oxygen level which is the major obstacle to PDT clinical application.As most tumors tend to develop a hypoxia environment which prevents the formation of ROS and further decreases antitumor therapeutic efficacy drastically.Therefore,the development of oxygen-independent therapeutic means is urgently demanded for efficient tumor treatment.Herein,a multifunctional GSPs^1,4-BDT@PDA-AIPH-cRGD nanosystem was successfully constructed to achieve the SERS imaging guided cancer treatment.Gold super-nanoparticles?GSPs?with superlattice structure were formed by successive self assembling of 5.8nm gold nanoparticles?GNPs?,modifying with the Raman signal molecule 1,4-BDT,and coating with dopamine?PDA?,then loading with 2,2'-azobis[2-?2-imidazolin-2-yl?propane]dihydrochloride?AIPH?,and functionalizing with a tumor targeting ligand cRGD.Here,GSPs serve as excellent enhancements of the Raman signal.While PDA can not only make the structure more stable and further enhance the Raman signal,but also convert NIR light into heat to kill the tumor cells.In addition,the elevated temperature could be used to break down AIPH to produce free radicals,which further killed tumor cells.The nanosystem ingeniously combined tumor targeting,photothermal treatment,oxygen independent generation of free radical into a single nanoparticle,resulting in the death of cancer cells in vitro and the significant inhibition of tumor growth in vivo,so as to achieve the synergistic cancer treatment guided by SERS imaging.This study provides basic research data for Raman guided cancer therapy new ideas for developing multifunctional nano-therapy platform.