Construction And Application In Tumor Therapy Of Light-sensitive Nanoparticles Based On Cyanine Dyes

The precise treatment of tumors with specific wavelengths of light mainly includes light-controlled drug release nano delivery system,photothermal therapy,and photodynamic therapy.The light source used in the light-controlled drug release nano delivery system is mainly short-wavelength ultraviolet light,which has poor permeability and can cause light damage to cells and tissues.Cyanine dyes,as promising photothermal agents show inherent near-infrared absorption and high molar extinction coefficient.In the photothermal therapy nano-system based on cyanine dyes,the poor photostability and low photothermal conversion efficiency of cyanine dyes,as well as poor biocompatibility and biodegradability of inorganic nanocarriers,limit its further clinical application.Therefore,it is of great significance to design light-sensitive nano-systems with high performance.Under slightly acidic conditions,hydroxyapatite（HAP）is degraded to phosphate,which has good biological safety.Herein,HAP is used to load the chemotherapeutic drug doxorubicin（DOX）,and then the light-sensitive molecular cyanine dye（Cy）and polyethylene glycol（PEG）are introduced to construct a nanodrug delivery system（HAP@DOX-PEG）with good biocompatibility.Under red light irradiation,Cy is cleaved by regioselective photooxidation of polyene,and the PEG chain is separated.The hydrated particle size of HAP@DOX-PEG is reduced from 414 nm to 178 nm,which improves the cancer cell uptake efficiency and tumor penetration capacity of DOX.In order to solve the problem of low drug loading rate of HAP,mesoporous silica（SiO₂）is used to construct a nano-drug delivery system SiO₂@DOX-Cy-PEG with pore-blocking caps.The drug loading rate of the nano-drug delivery system is 25.1%.PEG chains act as a cap structure to effectively prevent the premature release of the drug.Under irradiation,PEG deshielding from the nano-drug delivery system accelerates the release of DOX,which induces more cell apoptosis and effectively inhibits the growth of mice tumor.In order to improve the stability and photothermal performance of cyanine dyes,herein,an organic nano-formulation（HA@Cy-Cu）were fabricated using the coordination driven assembly of the carboxyl group of cyanine dye with Cu²⁺and further introducing hyaluronic acid（HA）through electrostatic interaction.The nanoparticles have high light stability and photothermal conversion efficiency（42.3%）.In cancer cells,Cu²⁺in the nanoparticles is reduced to Cu⁺by glutathione and further transforms from H₂O₂ to·OH,which lead to significant oxidative damage.After intravenous injection,the nanoparticles are actively targeted to the tumor site of mice through HA,and the tumors are completely ablated through the combination of photothermal and chemodynamic therapy.In order to improve the photothermal performance of cyanine dyes and reduce the side effects of chemotherapeutics,a molecular conjugate Cy-azo with H-aggregation enhanced PTT and sequential hypoxia activated chemotherapy is constituted.Due to the introduction of chemotherapeutic drugs,Cy-azo has superior photothermal conversion efficiency（39.3%）because of the enhanced H-aggregation ability.Moreover,the activated anti-cancer drug,nitrogen mustard,is released in the tumor hypoxic microenvironment,thereby greatly reducing the toxic side effects of chemotherapy.Encapsulated by the polymer fragments,the photothermal conversion efficiency of Cy-azo NPs further increased to 56.1%due to the high stability of the dye molecule H-aggregate.Cy-azo NPs are effectively accumulated in the tumor area through the enhanced permeability and retention effect by intravenous injection,and the tumors are completely ablated through the combination of photothermal and chemotherapy.