Mussel Foot Protein-Inspired Intelligent Hydrogel For Postoperative Cancer Therapy And Modulation Of Switchable Anticoagulant And Hemostatic Function

Clinically,surgery is the major form of intervention for comprehensive treatment of cancer,but higher local recurrence rate of cancer and post-operative tissue defect remain unaddressed.In this work,a robust injectable thermoresponsive nanocomposite hydrogel(PNAm-PDAAu)embedded with polydopamine(PDA)coated-gold nanoparticles(Au NPs)was first prepared by polymerization of N-arolyoyl glycinamide(NAGA)and acrylamide(AAm)without any chemical cross-linker through UV photoinitiation.The PNAm-PDAAu sol driven by near infrared light(NIR)heating was injected into the cavity of resected cancerous breasts of rats,thereby finely serving as a breast filler.After implantation,interval NIR light irradiation could mediate photothermal effect and concertedly controllable DOX release from the hydrogel,thus collectively preventing the recurrence of breast cancer and facilitating the breast reconstruction.Remarkably,this stable remoldable hydrogel was capable of being tracked by CT imaging owing to the intrinsic X-ray attenuation property of the loaded Au NPs.Although the PNAm-PDAAu exhibited an excellent therapeutic effect in postoperative breast cancer treatment,the strength of hydrogel was not high enough for serving as a bone implant material.Therefore,a high strength supramolecular copolymer hydrogel(PNDA-HAP)bearing hydroxyapatite(HAP)nanoparticles was prepared by one-step copolymerization of NAGA and N-methylacryloyl dopamine(DMA)without any chemical cross-linker through UV photo-initiation.The H-bond interactions inside the polymer networks was enhanced after copolymerization of DMA and this weak non-covalent interaction could increase the tear resistance of hydrogel due to the energy dissipation mechanism.Furthermore,the PNDA-HAP hydrogel exhibited better mechanical property and bone regeneration ability supposedly owing to the additional interaction of polymer chains-HAP nanoparticles.In tumor weak acid environment,p H-triggered DOX release of the PNDA-HAP hydrogel was accelerated,which was resulted from the reversible non-covalent interactions in hydrogel networks.It was shown that the recurrence of bone cancer was efficiently inhibited and the bone defect could be repaired due to the neutralization of HAP nanoparticles in tumor weak acid environment.On the other hand,blood coagulation of medical devices and excessive bleeding occur frequently in the cancer operation and post-operative therapy,but no efficient approach has yet been developed to concurrently solve the seemingly irreconcilable conflict between hemostasis and anticoagulation in a single material system.In the following study,we presented a novel strategy to engineer a smart indwelling needle with on-demand switchable anticoagulation and hemostasis activity by modifying the outside surface and inner surface of an indwelling needle with coagulant catecholfunctionalized chitosan coating and anticoagulant magnetic Fe NPs-dopamineconjugated heparin(Fe NPs-Hep DA),respectively.The results revealed that under a magnetic field,the Fe NPs-Hep DA-coated cannula inner wall maintained an excellent anticoagulation activity,ensuing the patency of the needle,from which the blood could to be drawn for 6 times in 3 h.After removing the magnetic field,the Fe NPs-Hep DA were shed off or aggregation occurred.Under this condition,the cannular inner surface lost anticoagulation activity,and when the needle was extracted from the vein,the anticoagulant CHCS coating on external surface served to prevent bleeding.In this work,we opens up new avenues for designing intelligent hydrogels as well as anticoagulation-coagulation coexistent biomaterials and biodevices.