Preparation Of Implantable Composite Materials And Its Application In Inhibiting Postoperative Tumor Recurrence And Metastasis

Triple-negative breast cancer（TNBC）is one of the most common breast cancer.It has the characteristics of high recurrence,high metastasis,and high fatality rate.It is the most important disease that threatens women’s life and health.How to achieve effective treatment of TNBC is a major challenge in the field of cancer treatment.At present,the clinical therapeutic efficacy of TNBC is not ideal.For example,the recurrence rate after surgical treatment is high.Chemotherapy and radiotherapy have obvious systemic toxicity.Targeted therapy is more expensive and challenged by to drug resistance.Although the method of local administration can greatly increase the local drug concentration,it still faces many challenges.For example,the treatment period of local drug delivery is short,and its biological safety still needs to be improved.High-dose photothermal and photodynamic therapy will cause irreversible damage to the body.Based on the above deficiencies,this paper designed implantable polymer and hydrogel drug-containing scaffolds,namely polycaprolactone（PCL）nanocomposite loaded with doxorubicin（Dox）and mesoporous silica nanoparticles（MSN）,and polyvinyl alcohol（PVA）self-healing hydrogel loaded with immune adjuvant（R837）and molybdenum disulfide（Mo S₂）for the suppression of postoperative TNBC recurrence and metastasis.The research content of this paper includes the following two aspects:1.A solvent-free method was used to prepare a nano-composite drug-containing scaffold with good dispersion of nanoparticles.MSN was used as a nano-carrier to load the chemotherapeutic drug Dox,and the drug loading efficiency could reach 9.83%.Subsequently,Dox@MSN and polycaprolactone（PCL）were mixed by grinding and pressed under heat in a mold to form a composite scaffold.By optimizing drug loading concentration and scaffold porosity,the amount and rate of drug release can be adjusted.A series of physical and chemical characterizations indicated that the nanocomposite scaffold had good mechanical properties and uniform drug distribution.The drug release period in vitro and in vivo was up to 50 days to meet the needs of postoperative chemotherapy for breast cancer.The nano-composite drug-containing scaffold could significantly inhibit the activity of tumor cells and effectively inhibit the tumor recurrence at the resection site after implantation into the body.At the same time,the composite scaffold has good biological safety.2.PVA self-healing hydrogel loaded with immune adjuvant（R837）and Mo S₂ was prepared.The hydrogel had good photothermal properties and self-healing properties.It exhibited certain tissue adhesion and deformability,which can better fit the surrounding tissues of the tumor resection site.Experiments showed that the drug release period in vitro and in vivo is about 5 days.In vitro cell experiments showed that the self-healing hydrogel could effectively inhibit the activity of cancer cells,and promote the maturation of dendritic cells（DC）and causing immune responses.Combined with immune checkpoint blocking agent,the hydrogel can effectively inhibate the activity of residual cancer cells at the tumor resection site of tumor resection and inhibit postoperative tumor recurrence and metastasis.The works in this paper provides new ideas and methods for inhibiting TNBC tumor recurrence and metastasis after surgery.