Modification Of Halloysite Nanotubes And Their Application In Cancer Therapy With Photothermal Therapeutic Agents And Chemotherapeutic Drugs

Malignant tumors pose a serious threat to human health and life.Traditional methods of cancer treatment?surgical resection,radiation therapy,and chemotherapy?have been widely used clinically but have some limitations,such as damage to normal tissues and drug resistance.In recent years,photothermal therapy?PTT?for cancer has become a research hotspot.The halloysite nanotubes?HNTs?have the advantages of high specific surface area,strong adsorption capacity,good water dispersibility,good biocompatibility and easy surface modification.Therefore,HNTs have the potential to serve as a carrier.In this paper,the surface modification method of HNTs and their potential application in photothermal therapy and imaging are discussed.?1?Halloysite nanotubes@carbon?HNTs@C?nanocomposites were synthesized by one-step hydrothermal carbonization of glucose.HNTs are effective in inducing heterogeneous deposition of carbonaceous materials on their surface,which results in the coating of an amorphous carbon layer on the HNTs.A variety of characterization methods demonstrate the successful preparation of HNTs@C.The effects of glucose loading and reaction time on the structure of nanocomposites were investigated.The thickness of surface carbon of HNTs increases with increasing glucose loading and reaction time.Bovine serum albumin adsorption experiments showed that HNTs@C has stronger protein adsorption capacity than the original HNTs.Hemolysis experiments showed that HNTs@C showed a reduced hemolysis rate compared to HNTs.In vitro cell culture experiments using HeLa cells showed that HNTs@C has lower cytotoxicity than the original HNTs.All of these indicate that HNTs@C have good adsorption capacity and biocompatibility,and they have potential applications in biomedical fields such as drug delivery vehicles.?2?Gold nanorods?GNRs?and doxorubicin hydrochloride?DOX?were loaded into the lumen of HNTs by rapid synthesis?2 min?and physical adsorption.The target molecule of folic acid?FA?is then conjugated to HNTs by reaction with bovine serum albumin?BSA?.The formation of GNRs in HNTs was verified by different techniques.Au-HNTs-DOX@BSA-FA showed a temperature rise of up to 26.8^oC after 8 min of 808 nm laser irradiation at 0.8 W·cm^-2.Functionalized HNTs exhibit a stronger chemotherapeutic effect under laser irradiation because the laser raises the temperature to promote DOX release.Au-HNTs-DOX@BSA-FA treated MCF-7 cells showed a7.4%survival rate after laser irradiation.In vivo chemical photothermal treatment of mice carrying4T1 showed that Au-HNTs-DOX@BSA-FA showed significant tumor targeting efficiency and good controlled release effect on DOX.In addition,nanoparticles exhibit rapid photothermal performance and ability to inhibit tumor growth.Due to the synergistic effect of chemical photothermotherapy,high efficacy was ensured under the premise of using low dose DOX of 0.32mg·kg^-1,and the toxicity of DOX to normal tissues was reduced.This novel chemical photothermotherapy nanoplatform provides a fast,efficient and inexpensive option for the treatment of breast tumors in vitro and in vivo.?3?Fe³⁺and Fe²⁺were coprecipitated by NH₃·H₂O to form Fe₃O₄ NPson the wall of HNTs.Then DOX and Py were adsorbed on the modified HNTs.Py was then polymerized on the surface of HNTs was polymerized with the aid of FeCl₃ to form HNTs@Fe₃O₄@PPy@DOX.The outer layer of PPy can act as photothermal agent and can encapsulate DOX and Fe₃O₄ for protection.The nano-platform can be guided to the tumor by external magnet,and the effect of combination of chemotherapy and photo-heat treatment on the tumor can be achieved by laser irradiation.At the same time,Fe₃O₄ has the ability of T2-weighted magnetic resonance imaging to guide the photothermal/chemotherapy of tumors by magnetic imaging.In vitro and in vivo experiments have demonstrated that the material can be targeted to the tumor to produce a photothermal temperature rise by laser irradiation to kill the tumor cells.Molecular magnetic resonance imaging of mice demonstrated that HNTs@Fe₃O₄@PPy@DOX is a novel therapeutic diagnostic agent that can be used for T2-weighted MR imaging in vivo.In addition,magnetic targeting of HNTs@Fe₃O₄@PPy@DOX allows for more effective ablation of tumors by external magnetic field control.