Development Of Mesoporous Carbon Nanospheres For Photoacoustic Imaging And Chemo-photothermal Cancer Therapy

Nanomaterials with strong light absorption in the near infrared region have broad biomedical applications.The development of nanomaterials with strong light absorption,high photothermal conversion efficiency and good biocompatibility is of great importance to photoacoustic imaging and tumor photothermal therapy.In this work,we synthesized a novel type of mesoporous carbon nanopheres（Meso-CNs）with strong photothermal conversion capacity and rich mesoporous structures,and we applied them:1)as contrast agents to achieve high-quality photoacoustic imaging,2)as photosensitizer for tumor chemo-photothermal therapy to provide a remarkably effective treatment for tumor.The results we obtained can be described as below:1.We synthesized a novel carbon nanospheres by a facile“silicon assisted”method.The transmission electron microscopy and scanning electron microscopy characterization results show that the carbon nanomaterials have a uniform particle size of 200 nm with a well-defined spherical morphology and a large number of pores can be clearly observed from the spherical framework.The N₂ adsorption-desorption isotherm of the Meso-CNs indicates the presence of mesopores and the pore sizes of the Meso-CNs are estimated to be².5 nm.The C1s X-ray photoelectron spectroscopy data reveals that the carbon surface of the Meso-CNs is dominated with C-C or C-H species along with smaller concentrations of C-O and O-C=O originating from the reaction of HF with carbon.Therefore,the Meso-CNs exhibit excellent dispersibility and stability in water because of their highly negative surface zeta potential of-35.5mV.2.We demonstrated that the Meso-CNs have broadband optical absorption and high photothermal conversion efficiency.UV–Vis–NIR absorption spectra of the Meso-CNs show that they have a broad absorption band from the UV to NIR wavelength range（300–1400 nm）,covering both the NIR-I and NIR-II optical windows.The absorption coefficients of the Meso-CNs were measured as 33.9 L g^-1cm^-1 and 29.1 L g^-1cm^-1 at808 nm and 1120 nm,respectively,which are 1.5–2 times higher than those of graphene,single-walled carbon nanotubes,and are comparable to the peak absorption coefficients of gold nanorods.The Meso-CNs also have high photothermal conversion efficiency,with photothermal conversion efficiencies as 35.8%at 808 nm and 46.3%at 1120 nm,respectively,higher than or comparable to contrast photothermal agents under the same experimental conditions.Furthermore,the Meso-CNs have good optical stability.No significant differences of their light absorption property and hydrodynamic radius were observed before and after laser irradiation.3.We demonstrated that the Meso-CNs has excellent drug loading capacity and applied them as drug carriers to achieve delivery and controlled release of anti-tumor drugs.We measured that the loading capacity of the Meso-CNs for anti-tumor drug doxorubicin（DOX）was up to³5.0 wt%（35 mg DOX per 100 mg Meso-CNs）,due to their highly mesoporous structures with appropriate pore size and porosity.We also found that the DOX release from the Meso-CNs was controllable.A solution with pH as low as 5.2 or near-infrared laser irradiation could accelerate the release of DOX.4.The Meso-CNs were explored in photoacoustic imaging as contrast agents and exhibited excellent photoacoustic properties.At the same mass concentrations in agar phantoms,excited by 808 nm laser light,the photoacoustic amplitude of the Meso-CNs was¹.2,¹.6,and².1 times of control contrast agents,graphene,single-walled carbon nanotubes,and gold nanorods,respectively.The contrast of photoacoustic imaging by Meso-CNs are both better than control contrast agents.Intensities of laser-induced photoacoustic signals after independent subcutaneous injections of Meso-CNs,graphene,single-walled carbon nanotubes,gold nanorods at the same concentration were compared.Mice injected with Meso-CNs showed much higher signal intensities than those injected with the other materials,consistent with results from the phantom experiment.5.We applied the Meso-CNs to tumor chemo-photothermal combined therapy and noticed its remarkably therapeutic effect.We used both MTT and Calcein-AM/PI co-staining methods to assess the photothermal effect for MCF-7 and HeLa cancer cells in vitro.The experimental results indicated a dose-dependent photothermal therapy effect after the cells were exposed to light radiation,for both wavelengths 808 nm and 1120nm.We further observed the therapeutic effect of the Meso-CNs in vivo.Under near infrared（NIR）laser irradiation,the local temperature of the tumors injected with DOX-loaded Meso-CNs rapidly rose to 65°C.Remarkably,tumor growth in the mice receiving the DOX-loaded Meso-CNs was effectively inhibited after NIR laser irradiation as a result of the combined chemo-photothermal therapy.The HE staining results of the tumor sections further confirmed that the cells in the tumors injected with Meso-CNs（or Meso-CNs+DOX）followed by laser irradiation were damaged significantly,whereas the tumor cells in control groups largely retained their normal morphologies with distinctive membrane and nuclear structures.Furthermore,the histological assessment confirmed that there was no damage or inflammation in the major organs of each group.