Fabrication Of Self-oxygenated Nanocomposites And Its Application In Photodynamic Therapy

Cancer is one of the diseases that endanger human health.In recent years,photodynamic therapy?PDT?has attracted much attention due to its advantages such as minimally invasive and low toxic side effects.Hypoxia in the solid tumor,low tumor accumulation and limited light penetration depth of photosensitizers?PS?have become the most important problems that limit the development of PDT.At present,nanotherapeutic agents that can release drugs,photosensitizers and oxygen by tumor microenvironment?TME?or light-trigger have attracted great attention.However,the preparation methods of such nanomaterials are complicated and there are still some problems in the controllability and real-time tracking of drug and oxygen release.In this thesis,we designed and synthesized several novel nanotherapeutic agents via a rather simple method to achieve excellent phototherapeutic performance characterized by deep penetration,TME response,NIR-light-trigger,and O₂ self-supply.The main contents are list as follow.?1?New nanostructured MnO₂-based nanotherapeutic agents?BHMI NPs?were designed to achieve excellent phototherapeutic performance characterized by NIR-light-mediation,deep diffusion via TME response and O₂ self-supply.In this design,hydrophobic NIR dye IR780 and bovine serum albumin?BSA?were adsorbed onto honeycomb MnO₂ via electrostatic interaction and Mn-N coordination bonding,and honeycomb MnO₂ plays key role to enhance tumor accumulation and deep intratumoral diffusion.First,honeycomb MnO₂ nanoparticle were prepared by a rather simple method,and then,the near-infrared photosensitizer IR780 was adsorbed onto honeycombed MnO₂ nanoparticle via electrostatic interaction and coordination of manganese ions.Furthermore,in order to increase the cycling stability and biocompatibility of nanomaterials,bovine serum albumin?BSA?was modified to the surface of the as-prepared nanomaterials by hydrogen bonding between BSA and MnO₂ nanoparticles,and finally the functionalized nanotherapeutic agents?BHMI NPs?were obtained.The ex vivo and in vivo NIR fluorescence imaging results demonstrate that the honeycomb nanostructure of HMIB NPs facilitates the high tumor accumulation of hydrophobic IR780 via enhanced permeability and retention?EPR?effect after intravenous injection.The immunofluorescence results demonstrate that the TME response of HMIB NPs not only provides O₂ for relieving hypoxia but also reduces size for improving deep intratumoral diffusion.As a result,under the synergy of NIR fluorescence imaging,photothermal effect and PDT of IR780 with TME responsive size-change and O₂ self-supply of honeycomb MnO₂,the HMIB NPs have achieved all-in-one NIR fluorescence and photothermal dual-model imaging guided synergistic PDT/PTT under a single-wavelength NIR light irradiation.?2?First,silica hybrid nanoparticles with near-infrared photosensitizer?IR780?and fluorescein?rhodamine B?was prepared.Then,polyvinylpyrrolidone?PVP 40 K?was adsorbed on the surface of the silica to provide binding sites for the subsequent absorption of H₂O₂.In this design,the near-infrared dye IR780 was used as a photosensitizer and a photothermal reagent to trigger oxygen and dyes release and carrier decomposition.The experimental results demonstrate that the as prepared HPIBS NPs showed excellent performance in on-demand O₂ self-sufficient and degradable properties under NIR laser irradiation.Such a nanosystem provides a potential platform for improved therapeutic efficacy in anticancer therapy.