Construction Of Boron-based Multifunctional Nanoplatform And Application Of Tumor Synergistic Chemotherapy/Low-Temperature Photothermal Therapy

Traditional methods for tumor treatment usually face some unavoidable side effects.With the continuous development of materials and nanotechnology,plenty of smart drug carrier materials have emerged and are used in the research of tumors and other major diseases.In recent years,photothermal therapy（PTT）has been widely studied in tumor treatment due to its high treatment efficiency and low side effects.PTT is usually combined with other treatment methods to build a multifunctional synergistic treatment nanoplatform,and has showed excellent treatment effects.However,cancer cells are easily tolerant to heat stress after thermal treatments.Therefore,to ensure the therapeutic effect,relatively high local temperature（>50℃）is often required in photothermal therapy.However,such high temperatures will create damage to the healthy organs and tissues near the tumor site.Therefore,providing effective photothermal therapy under mild conditions will be a potential PTT strategy.Heat shock protein（HSP）has been proven to be an important factor for activating tumor defense mechanisms,and it plays a vital role in the tolerance of cells to higher temperature.In order to develop an effective antitumor strategy with relatively low side effects,an innovative boron-based multifunctional nanoplatform was constructed in this work for synergistic chemotherapy/low temperature photothermal therapy（PTT）.Firstly,two-dimensional boron nanosheets were prepared by thermal oxidation etching and liquid phase exfoliation technology,and modified by H₂N-PEG-NH₂ to make the nanoparticles have better biocompatibility.Then the platform is functionalized with the cRGD peptide to permit nanoparticles targeting towardα_vβ₃ integrin over expressed on tumor cells,promote the uptake of nanoparticles by tumor cells and exert subsequent therapeutic effects.The nanoparticles were further loaded with the anti-tumor drug doxorubicin（DOX）and a heat shock protein inhibitor（17AAG）,and the loading capacity of DOX（60.3%） and 17AAG（41.7%）（w/w） was obtained,respectively.The resultant DOX-17AAG@B-PEG-cRGD system shows both pH-controlled and near-infrared（NIR）-induced DOX and 17AAG release.It also gives significantly enhanced cellular uptake in cancerous cells over healthy cells.At the same time,the release of 17AAG can effectively inhibit the expression of heat shock protein 90（HSP90）in tumor cells,thereby alleviating the heat tolerance of the cells.The presence of 17AAG permits low-temperature PTT to be combined with chemotherapy from DOX,resulting in highly effective anticancer activity.This has been confirmed by both in vitro assays and using an in vivo murine cancer model.In summary,the DOX-17AAG@B-PEG-cRGD nanosystem prepared in this study has good biocompatibility,and can achieve effective aggregation at the tumor site through passive（EPR effect）and active targeting.The chemotherapy/photothermal synergistic treatment is realized under the mild conditions,,and it shows excellent antitumor effect.It is expected that such multifunctional nanoplatform can serve as a promising candidate for cancer therapy.