Novel Multifunctional Degradable Photothermal Agent For Tumor In Situ Synergistic Therapy

Gold-based nanoparticles are the only U.S.Food and Drug Administration-approved clinical phase ? medical photothermal diagnostic agents with the photothermal properties and good biocompatibility,which are caused by Landau damping effect and play an important role in tumor treatment.However,in order to achieve higher photothermal conversion efficiency and enrichment rate,most gold-based nanomaterials are usually designed to be larger than 20 nm in size,which are not suitable for in vivo metabolic clearance,and long-term retention may cause biological toxicity.In addition,the penetration depth dependence of the near-infrared(NIR)laser and the non-uniformity of the heat distribution,inducing it is impossible for single photothermal therapy to eradicate the tumor.Based on the problems,this thesis used liposomes as template and chloroauric acid as precursor synthesized biodegradable honeycomb-like gold nanoparticles(HGNs),which has good monodispersity,large NIR light absorption cross section,and excellent degradability.Based on HGNs,two multifunctional tumor treatment integrated platforms including thermo-radiotherapy(PT-RT)and chemo-phototherapy(CPT)were established to achieve multiple synergistic treatments.The synergistic treatments completed ablation of tumors with minimal damage,effectively eliminating small hidden metastases during tumor treatment,and inhibiting the tumor recurre.For PT-RT,SW1990 orthotopic pancreatic cancer was adopted as the therapy model.Through the PTC puncture needle minimally invasive intervention method,it entered the deep abdominal cavity for local irradiation therapy and low-dose 125I radiotherapy,which avoided damage to normal tissues induced by high-energy external radiation.HGNs acted as both internal photothermal agents and radiosensitizers,achieving a 98%tumor inhibition rate.For CPT,4T1 breast cancer was adopted as the therapy model.HGNs were used to encapsulate the exogenous enzymes.The NIR laser was explored to trigger the release of the enzyme,achieving a 100%tumor inhibition rate and greatly reduces chemotherapy drugs cause systemic toxicity.Over all,a multifunctional integrated tumor therapy platform based on degradable gold nanoparticles was extablished,holding a promising future for clinical translation.