Functionalization Strategy Of Magnetic Iron-Based Nanomaterials For Tumor Diagnosis And Treatment

Cancer has caused serious harm to human health and lives.However,the early diagnosis and efficient treatment of tumors remain challenging.The development of functional nanomaterials provides a new opportunity for precise diagnosis and efficient treatment of tumors.Iron-based nanomaterials possess outstanding advantages such as biocompatibility,controllability of morphology and size,tunability of functional components,and surface chemical modification,which promote their wide utility in tumor molecular imaging,controlled drug delivery,and tumor magnetothermal treatment in various biomedical scenes.The design of functional nanomedicine with magnetic iron-based nanomaterials has broad application prospects and clinically transformable chances.Thus,this article presented three novelty functional diagnosis and treatment systems based on magnetic iron-based nanoparticles and combined with the special pathological characteristics of the tumor microenvironment,aiming to improve the accuracy of magnetic resonance imaging(MRI)diagnosis of tumors and treatment effectiveness.These works are summarized as follows:A functional theranostic agent holds great promise for tumor management.Here,a tumor microenvironment(GSH)-responsive nano-platform(mPEG@TAT@Fe3O4)based on Fe3O4 nanoparticles was designed for MRI-guided magnetothermal tumor treatment,aiming to improve the intravenous administration of magnetothermal agents and difficulty in monitoring tumor treatment.mPEG modification endowed the nanomedicine with longer blood circulation time and weakened non-specific cell uptake.In the tumor site,tumor-specific reduction of the pathological environment(GSH)triggered the shedding of the mPEG shell to expose the inner TAT peptide,which promoted the internalization of Fe3O4.The protection-shedding-local uptake cascade enhancement strategy effectively increased the accumulation of nanomedicine in tumors,and achieved MRI-guided tumor hyperthermia therapy and immune-favorable tumor microenvironment,thereby presenting a promising method for improving tumortargeted delivery and immune activation.The early detection of metastases is vital to prolonging the survival of tumor patients.Next,a target-response-signal amplification cascade MR nanoprobe(UMFNPCREKA)based on manganese-doped ferrite nanoparticles was constructed to detect small tumors/metastasis by MRI.The high level of fibronectin,low pH,and H2O2 containing tumor pathological characteristics have been used as the inducer of UMFNPCREKA for multi-level response signal amplification.UMFNP-CREKA is recruited to the margin of tumor metastases by the binding of CREKA with fibrin-fibronectin complexes,and then release of manganese ions(Mn2+)to the metastasis in response to pathological parameters(mild acidity and elevated H2O2).The localized release of Mn2+and its interaction with proteins affects a marked amplification of Ti-weighted magnetic resonance(MR)signals,thereby providing an abundance of anatomical and functional imaging information of large tumors,experimental lung metastases,and systemic spontaneous metastases.In addition,UMFNP-CREKA achieved the detection of 0.39 mm metastases,significantly extending the previously reported detection limit of MRI probes.This work provided a reference idea for the development of a smart multiparameter response nano-diagnostic drug delivery system.Last,a spatiotemporal controlled CD47nb release integrated bacterial robot delivery system based on Fe3O4 nanoparticles was constructed to perform the precisely controlled release of nano-drugs at tumor sites.Through genetic engineering of H1pACD47nb plasmid I,bacterial robots expressed the fusion protein of histone-like protein A(H1pA),which ensured the affinity to heparan sulfate proteoglycan(HSPG)that is overexpressed in colon cancer,to realize the robot’s tumor-targeting instructions;Meanwhile,amounts of CD47nb expression was induced.The signal decoding unit of Fe3O4 nanoparticles converted the magnetic field(MF)signal into a heat signal(42℃),and induced the temperature-sensitive plasmid Ⅱ to express the bacterial lysis protein phiX174-E(signal process),causing bacterial lysis and CD47nb release(signal output).Through the precise control of MF signal,the metabolic lysis behavior of bacteria in the body could be controlled,and the tumor-specific time and space controllable release of CD47nb would be carried out.The unique immunogenicity of the bacterial lysate and CD47nb could trigger a synergistic immunomodulatory effect,elicit stronger innate immunity and adaptive immune response,and induce robust systemic anti-tumor immunity.These Fe3O4 nanoparticles modified bacterial robot platforms showed a great promise in precise and controllable drug delivery,and potent tumor immunotherapy.