Nb₂C@Dox Microneedle For Synergistic Photothermal-chemo Treatment Of Superficial Tumors

Photothermal chemotherapy is a new method of synergetic tumor therapy,which combines photothermal therapy with drug chemotherapy to achieve more effective treatment.Photothermal agents are important materials for photothermal chemotherapy,mainly used in the photothermal generation and drug loading.Traditional photothermal agents usually have limitations in biocompatibility,biodegradability,stability,drug loading,spectral absorption and photothermal conversion efficiency.MXene nanosheets are new materials,which not only have good biodegradability and biocompatibility,but also have large drug loading surface area.More importantly,MXene has excellent absorption ability in the near infrared（NIR）regions Ⅰ and Ⅱ,and exhibits good photothermal conversion ability,so it is very suitable for use as photothermal agent.Polymer microneedle（MN）is a rapid development of drug delivery technology in recent years.Compared with the traditional drug delivery,it has advantages of minimally invasive,painless,efficient,accurate,non-systemic toxicity and has gradually become a hot spot in the medical field.In this paper,a dissolvable microneedle system based on 3D printing and micro molding technology is developed for the efficient delivery of Nb₂C photothermal-agent,which is a member of the MXene family,and the chemotherapeutic agent Doxorubicin（Dox）to achieve photothermo-chemical synergistic therapy of superficial tumors.The main work is as follows:（1）Nb₂C nanosheets were prepared and characterized.In this paper,Nb₂C nanosheets were prepared by chemical etching method.The synthesis of Nb₂C nanosheets was verified by XRD and EDS.The morphology and size of Nb₂C nanosheets were characterized by TEM imaging and dynamic light scattering（DLS）.Functionalization of Nb₂C nanoplates and loading of DOX were realized by conjugation reaction.（2）A dissolvable Nb₂C@DOX MN system containing Nb₂C and DOX was designed and fabricated.In this paper,the positive mold was first formed based on 3D printing technology,then the template was formed by polydimethylsiloxane（PDMS）,and finally the microneedles containing Nb₂C and DOX were formed by a two-step process.The morphology of Nb₂C@DOX MN was characterized by con focal microscopy and scanning electron microscopy（SEM）,and its mechanical strength was confirmed by a mechanical tester.（3）The performance of Nb₂C@DOX MN system was evaluated in vitro.The results show that the Nb₂C@DOX MN system is an efficient,stable and reproducible heating system.Three minutes after insertion into the isolated skin,the microneedles dissolved;In NIR-Ⅰ radiation,can reach 60 degrees in a minute,and can effectively release drugs.（4）The antitumor activity of Nb₂C@DOX MN system was evaluated in vivo.This system realized the accumulation of Nb₂C and DOX in mouse superficial tumor.Under NIR-Ⅰ radiation,the drug release was realized.Compared with the control group（drugfree microneedles,Nb₂C,or DOX only）,the proposed system achieved more effective treatment of superficial tumors.The tumor size was significantly reduced after four treatments.This paper proposes a novel microneedle system,which provides a more effective tool for photo-thermochemical synergetic therapy of superficial tumors.