A Light-activated Plasmonic-nanocatalyst For Oxygen Self-supply Photocatalytic Therapy

Cancer is a disease with a high mortality rate and a low cure rate.Current cancer treatments include surgery,radiotherapy,chemotherapy,and biotherapy,but due to their side effects and poor prognosis,it is difficult to meet the current clinical needs.Compared with natural enzymes,nanoenzymes have attracted wide interest due to their high stability,low cost,and ease of preparation,especially in the field of cancer treatment.Nanozymes can target tumor cells through EPR effects and targeting peptides.Nanozymes kill cancer cells in two ways:the first is to increase ROS in the body directly through the oxidative enzymes?OXD?and peroxidase?POD?enzyme activities of the nanozymes;the second is indirect killing,which is related to the catalase?CAT?or superoxide dismutase?SOD?enzyme activity of the nanozymes,which can reduce the hypoxia of the tumor microenvironment through the help of light,sound or chemical pathways,thereby enhancing the efficacy of cancer treatment.In recent years,the nobel metal gold nanorods?Au NRs?have been widely studied due to their tunable local surface plasmon resonance effect and nanozyme activity.The catalytic activity of a single Au NRs is very limited.Gold-based nanomaterials,especially gold-platinum-based composite nanoparticles of various structures,due to their OXD,CAT,and POD and SOD has attracted widespread attention.It is well known that by adjusting the size,morphology and composition of nanozymes,the catalytic performance of nanozymes can be well controlled.In this paper,we first designed and synthesized dumbbell-shaped platinum-tipped-gold nanorods?Pt-Au NRs?,and charactered the structural morphology and elemental composition of Pt-Au NRs by transmission electron microscope?TEM?,X-ray diffraction?XRD?pattern,high-resolution transmission electron microscopy?HRTEM?and High-angle annular dark-field scanning transmission electron microscopy?HAADF-STEM?;the surface potential of Pt-Au NRs was detected by a Zeta potential analyzer.The results showed that Pt-Au NRs are dumbbell-shaped nanorods with an aspect ratio of about 3.45,with uniform size and the surface is modified with methoxypolyethylene glycol thiol(MPEG₅₀₀₀-SH),indicating that Pt-Au NRs were successfully prepared.Furthermore,it was verified by electrochemical analysis that Pt-Au NRs can effectively transfer hot electrons under laser irradiation due to its excellent structural effects.Then,ESR and DPBF detection methods were used to verify that Pt-Au NRs had excellent oxygen and singlet oxygen?¹O₂?production ability under 808nm laser irradiation,that is,it has the properties of light-activated CAT enzymes and photocatalysis to promote the production of ¹O₂.Human breast cancer cells?MDA-MB 231?were tested for cell activity after incubation with different concentrations of Pt-Au NRs by CCK-8.As anticipated,the results showed that Pt-Au NRs had good biocompatibility in vitro without laser.After808nm laser irradiation,the cytotoxicity of Pt-Au NRs increased with the increase of its concentration;the co-localization of Pt-Au NRs and lysosomes was observed by confocal microscopy to determine the cell uptake of Pt-Au NRs.As a result,the surface Pt-Au NRs can enter the lysosome,and lysosomal escape will occur;DCFH-DA probe and confocal microscopy were used to detect the Pt-Au NRs producing reactive oxygen species(?Reactive oxygen species,ROS?.In addition,to investigate the anti-tumor effect in vivo,the breast cancer-bearing mice model was established.In vivo anti-tumor experiments have demonstrated that Pt-Au NRs can significantly inhibit tumor growth under 808nm laser irradiation and significantly reduced tumor volume,which showed excellent photocatalytic treatment effects.Herein,we constructed a highly efficient nanocatalyst?named Pt-Au NRs?to enhance the efficacy of photocatalytic therapy and against hypoxic tumors by light-activated self-supplied O₂ and accelerating ¹O₂generation in the tumor site.The Pt NPs were able to selectively deposited on the ends of Au NRs,which made the light-induced hot electrons transfer form Au to Pt.Under 808nm laser irradiation,the transferred plasmon-generated electron could activate the CAT-like activity of Pt-Au NRs to catalyze endogenous H₂O₂ to generate O₂ at the hypoxic tumor site and activated the OXD-like activity of Pt-Au NRs to generation cytotoxic ¹O₂ for alleviating tumor hypoxia and enhance photocatalytic therapy.In in vivo experiments,the Pt-Au NRs exhibit superior reversible regulated catalytic activity by laser irradiation and a dramatically strong ability to ablate tumors in vivo with extremely low toxicity,it not only enhance the generation of ROS but also improve the hypoxic environment in the tumor.The designed light-activated plasmonic-nanocatalyst is a promising tumor oxygen bomb by sequential nanocatalytic reaction,which demonstrates the proof of catalytic nanomedicine concept in effective tumor therapy.