Tumor Microenvironment-responsive Functional Materials For Multimodal Cancer Therapy

The high incidence and mortality of malignant tumors have become one of the major diseases threatening human health.At present,early detection,early treatment and reduced side effects are the best ways to treat cancer.Current conventional treatments are not effective in treating cancer due to poor prognosis and side effects.Tumor microenvironment（TME）is a special pathological environment composed of tumor cells and extracellular matrix（ECM）,which regulates the complex biological behavior of tumors.Compared with normal cells,it has characteristics of hypoxia,low p H,and hydrogen peroxide（H₂O₂）overexpression,providing opportunities and directions for novel targeted cancer therapy.In recent years,the therapeutic system based on TME-specific constructs has made great progress.The main research of this thesis is as follows:（1）p H-programmed responsive nanoplatform for synergistic cancer therapy based on single atom catalystsGiven the advantages of porous and high atomic utilization of single-atom iron-containing catalysts（SAF NPs）,we designed a p H-programmed responsive nanodrug delivery and synergistic therapeutic nanoplatform（Ca CO₃@SAF NPs@DOX）.SAF NPs was used as carrier to load chemotherapy drug doxorubicin（DOX）,then Ca CO₃was mineralized in situ,and encapsulated with A549 cell membrane（CM）to obtain an excellent biocompatibility and targeting nanoplatform.After targeting homologous cancer cells by CM,the Ca CO₃mineralization layer was decomposed to release Ca²⁺to form calcium ion interference therapy（CIT）and DOX to form chemotherapy（CT）under the weak acidic response.Besides,SAF NPs can undergo Fenton-like reaction and in situ produce·OH to generate chemodynamic therapy（CDT）.Therefore,the designed nano-system not only enables effective drug delivery,but also targeted multimodal combination therapy can achieve efficient and precise tumor treatment.（2）Escherichia coli Based in-Situ Triggerable Probe for Sensitive Diagnosis and Deep Penetration Therapy of CancerIn this work,to achieve imaging diagnosis and in-depth treatment of tumors,Escherichia coli（E.coli）was used as carrier to reduce HAu Cl₄in-situ,and then the photosensitizer（riboflavin,Rf）and luminescent reagent（luminol）were modified to obtain ROS self-amplified nanoprobe（E-Au@Rf@Lum）.In the overexpressed H₂O₂environment of tumor cells,the blue-violet light emitted by luminol allows both chemiluminescence（CL）imaging and Rf excitation by chemiluminescence energy resonance transfer（CRET）to generate ROS for photodynamic therapy（PDT）.In addition,the E.coli catalase-containing that catalyzes H₂O₂to produce O₂,which in turn alleviates hypoxia in PDT.Finally,ROS generated by Rf excitation can promote CL intensity of luminol,to form a cyclic amplification process,and the abundant ROS can break down the dense ECM and penetrate into the tumor for PDT.The study combines imaging diagnosis and treatment of cancer,and proposed integrated diagnosis and treatment system provides a research idea for early detection and treatment of tumors.