Construction Of Nitric Oxide Releasing Polydopamine Nanoparticles And Application Of Tumor Synergistic Therapy

Cancer is a serious threat to human health and life safety.However,the accurate diagnosis and treatment of cancer is difficult to achieve limited by the current treatment methods and the complex nature of tumor.In order to improve the therapeutic effect,the drug delivery system（DDS）using nanomaterials as the carrier has come into people’s view.Mussel bionic polydopamine（PDA）has been widely used in the release of tumor drugs due to its good biocompatibility and modifiability.Meanwhile,due to its good photothermal conversion ability,polydopamine can be used as photothermal conversion agent in tumor photothermal therapy（PTT）.Gas therapy based on nitric oxide（NO）has become a potential treatment for cancer,which can be combined with multi-mode combination therapy,providing a new possibility for overcoming cancer.However,delivery of NO gas by conventional means often results in the haphazard diffusion of therapeutic gas in the body,causing harm to normal cells,resulting in poor therapeutic effectiveness.It has been shown that natural NO donor L-arginine（L-Arg）can react with reactive oxygen species（ROS）to produce NO.Considering that photodynamic therapy（PDT）can provide ROS for L-Arg,release of NO gas in situ becomes possible.In this study,we designed and constructed an nitric oxide releasing antitumor nanoplatform AI-MPDA@BSA NPs.MPDA nanoparticles（NPs）were prepared by template method,loaded with L-Arg and photosensitizer IR780,and coated with bovine serum protein（BSA）to enhance biocompatibility.Under the irradiation of 808 nm near-infrared laser（NIR）,AI-MPDA@BSA NPs produces singlet oxygen（¹O₂）,a portion of which can convert L-Arg to NO,achieving the combination of PDT and gas therapy.In addition,due to the photothermal properties of PDA,the distribution of NPs in the body can be effectively tracked through photoacoustic imaging（PAI）.As expected,the nanoplatform has ideal particle size,can be effectively taken up by tumor cells after intravenous administration,and has the ability to release NO gas in situ,synergistic with PTT and PDT.Both in vitro and in vivo studies have demonstrated that the multifunctional platform is more effective than single therapy,AI-MPDA@BSA NPs has a significant inhibitory effect on cancer cells and tumors.And also has excellent biocompatibility,no significant toxicity or side effects were found during treatment.