Study On A Novel Core-shell Gold Nanomaterial For NIR Mediated Antitumor Photothermal Therapy

Photothermal therapy (PTT) employs photosensitizing agents taken up by cells to generate heat from near-infrared (NIR) light, leading to photoablation of cancer cells. However, complete tumor eradication by PTT alone is difficult because heterogeneous heat distribution can lead to the accumulation of a sub-lethal thermal dose in some areas of the tumor. High absorption in the NIR region for a photosensitizing agent is a key to obtain an efficient PTT effect. Herein, we fabricated a novel NIR photosensitizer, Doxorubicin (DOX) inserted gold nanospheres (DAuNS), where DOX as a core and gold as a shell.Our work presents a new, simple method to load a drug into the nanoparticles with similar synthesis process of hollow gold nanoparticles (HAuNS), by changing the stabilizer and adding Doxorubicin hydrochloride (DOX’HCl) into the reaction medium. DAuNS may be a promising nanoparticle for cancer therapy with controllable synthesis, small size, narrow size distribution and "two punch" efficacy of photothermal therapy with chemotherapy.The novel DOX inserted gold nanospheres, called DOX-Au core-shell nanoparticles (DAuNS), the average size distribution is 58.6±1.6 nm,polydispersity index is 0.0412, zeta potential is 14.6±0.5 mV. Interestingly, DAuNS presented a significantly enhanced plasma resonance absorption in the NIR region, compared to HAuNS alone or the complex of DOX-HCl and HAuNS (DOX@HAuNS), inducing more efficient photothermal conversion and stronger tumor-cell killing ability under NIR laser irradiation. In the photothermal conversion assay, under the same Au concentration and irradiation condition, DAuNS and HAuNS could reach approximately 70 and 55℃ after a 10 min-exposure in vitro and 60 and 50℃ after a 5 min-exposure in vivo. Furthermore, DAuNS presented a more stable photothermal coupling property due to the insert of DOX, compared to HAuNS. We observed that, after several irradiations, DAuNS showed no significant change in NIR plasmon absorption (-800 rim), indicating a photothermal coupling property suitable for PTT. TEM imaging showed that most of the DAuNS kept intact after three irradiations. DAuNS produced the photothermal effect under NIR laser irradiation, which subsequently triggered the release of DOX molecules from the nanospheres. The triggered release of DOX depended on the pH environment and the laser. At a slightly acidic environment (pH=5.5), where the tumor thrived, the release of DOX maximized under NIR laser irradiation, accumulated releasing of DOX is more than 90%; but less than 35% at pH=7.4 without laser irradiation. Antitumor activity assay also showed, under the mediation of the NIR laser, DAuNS exerted the strongest antitumor activity, which could be attributed to the dual modalities of cell killing, enhanced photothermal ablation and chemical toxicity. The novel nanomaterials of DAuNS may be a promising nanoparticle for cancer therapy with controllable synthesis, small size, narrow size distribution and "two punch" efficacy.