Piezoelectric Catalysis Of Bismuth Ferrite Nanoparticle Drug Delivery System And Cervical Cancer Therapy Research

Cancer constantly threatens human life and health,and more and more treatment strategies have been developed.Traditional chemotherapy,surgical excision and radiotherapy lead to unsatisfactory therapeutic effects due to poor targeting,high toxicity and side effects and high recurrence rate.Piezoelectric catalytic therapy,triggered by mechanical energy,produces reactive oxygen species with high oxidation potential through the release of electrons-holes in the oxidation-reduction reaction,resulting in increased oxidative stress at the tumor site,thus damaging tumor cells.The oxygen produced can effectively relieve the hypoxic state of the tumor site and reduce the expression of hypoxia-inducing factors.Piezoelectric catalytic therapy has the advantages of increasing tissue penetration depth,non-invasive and high therapeutic efficiency.It has become a new strategy for tumor treatment to kill tumors based on the active substances produced by piezoelectric catalytic therapy.Bismuth ferrite（BiFeO₃）is a traditional ferroelectric semiconductor material with good piezoelectric catalytic properties.Under ultrasonic stimulation,BiFeO₃can decompose water by piezoelectric catalysis to generate oxygen and active oxygen.At the same time,the internal electric field will form,resulting in band bending,making electron holes difficult to compound,which is conducive to the generation of reactive oxygen species.Dasatinib（DAS）is an anti-tumor drug that reduces collagen content to inhibit cytoplasmic matrix synthesis,thereby reducing the solid pressure of the stroma and allowing the drug to penetrate deeper into the tumor,breaking the barrier to drug delivery.Hyaluronic acid（HA）is an acidic mucopolysaccharide,a major component of the extracellular matrix.HA can bind to CD44 receptors highly expressed by tumor cells to improve drug targeting and biocompatibility.In this study,BiFeO₃nanosheets with piezoelectric catalytic properties were used as the base.By loading chemotherapy drug DAS and modifying hyaluronic acid HA,a BiFeO₃/DAS@HA nano-drugs delivery system was constructed to further study the in vitro and in vivo tumor treatment mechanisms and effects of nano-drugs.Firstly,piezoelectric bismuth ferrite nanosheets were synthesized by hydrothermal method.Meanwhile,dasatinib（DAS）was loaded onto BiFeO₃nanosheets by electrostatic adsorption and then hyaluronic acid（HA）was modified to improve the targeting ability and biocompatibility of the drug,and finally,the bionic nanodrug delivery system（BiFeO₃/DAS@HA）was constructed.HA can bind to CD44 receptor which is highly expressed in tumor cells,realizing effective accumulation of drugs in tumor sites.When BiFeO₃/DAS@HA reaches the tumor area,under the excitation of ultrasound（US）,electrons and holes are separated,and the holes react with the water at the tumor site to produce hydroxyl radical（·OH）and reduce the liquid pressure of tumor interstitial.Electrons can convert oxygen into superoxide anion radical（·O₂^-）,which further reacts with the hole to produce singlet oxygen（¹O₂）to induce apoptosis of tumor cells.The oxygen produced improved the hypoxic environment at the tumor site and reduced the expression of hypoxic-inducing factors.DAS,as a chemotherapy drug,can kill tumor cells,reduce the content of collagen,inhibit the synthesis of extracellular matrix（ECM）,reduce the solid pressure of tumor interstitial,promote more drugs to reach the deep region of tumor,and improve the penetration efficiency of nano drugs.BiFeO₃/DAS@HA showed excellent anti-tumor effects in vitro and in vivo treatment.BiFeO₃/DAS@HA group had the highest apoptosis rate under the US treatment,significantly inhibiting tumor growth in mice.In conclusion,the design achieves the synergistic treatment strategy of piezoelectric catalytic therapy and chemotherapy to improve the anti-tumor effect by reducing the interstitial pressure of tumor.