黑色素基靶向纳米药物用于乳腺癌的光热治疗  

Melanin-based Targeted Nanodrugs for Photothermal Therapy of Breast Cancer

作　　者：孙菁华 郭春燕 董杰 张瑞平[1] SUN Jinghua;GUO Chunyan;DONG Jie;ZHANG Ruiping(Department of Radiology,First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一医院放射科,太原030001

出　　处：《高等学校化学学报》2023年第8期43-53,共11页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:81801767,32271429);山西省自然科学研究面上项目(批准号:202203021211243);山西医科大学校博士启动基金(批准号:03201549)资助。

摘　　要：为提高小尺寸黑色素纳米颗粒(MNP)在肿瘤部位的靶向效应,设计合成了一种在肿瘤微酸性环境下可降解的羟基磷灰石杂化介孔氧化硅(MSN/HAP)对其进行负载,结合RGD导向肽构建了一种新型靶向纳米药物(MAN/HAP-MNP-RGD),用于小鼠乳腺癌的多模态成像和光热治疗.对纳米颗粒进行了理化性能、细胞和活体实验.结果表明,颗粒尺寸约为60 nm,MNP的负载量为37.7%,在微酸性环境中呈现较好的降解性,且纳米颗粒的光热转化效率(η)高达40.29%.细胞实验结果也证明了纳米颗粒的高效摄取和对细胞的光热杀伤效果.此外,光声成像和磁共振成像结果表明,纳米颗粒在肿瘤部位表现出更高的累积和更长时间的滞留.活体实验结果证明,MAN/HAP-MNP-RGD具有最佳的治疗效果且具有很高的生物安全性,展现出潜在的应用前景.To improve the targeting effect of small-sized melanin nanoparticles(MNP)at tumor sites,a hydroxyapa⁃tite hybrid mesoporous silica(MSN/HAP),which is degradable in tumor micro-acidic environment,was designed and synthesized for loading,and a novel highly targeted nanodrug(MAN/HAP-MNP-RGD)was constructed in combi⁃nation with RGD-directed peptide for multimodal imaging and photothermal therapy of mouse breast cancer.The physicochemical properties of nanoparticles,cellular and in vivo experiments were examined and the results showed that the final particle size was approximately 60 nm,the loading of MNP was 37.7%,the nanoparticles showed good degradability in a slightly acidic environment,and the photothermal conversion efficiency of the nanoparticles was 40.29%.In addition,the results of photoacoustic imaging and magnetic resonance imaging showed that the nanoparticles showed higher accumulation and longer retention time at the tumor site.Finally,the in vivo experiments demonstrated that MAN/HAP-MNP-RGD has the best therapeutic effect and high biosafety,showing potential applications.

关 键 词：羟基磷灰石杂化介孔氧化硅 黑色素纳米颗粒 光声成像 磁共振成像 光热治疗 

分 类 号：O613.72[理学—无机化学] O631[理学—化学]