可降解介孔氧化硅提高黑色素诊疗一体化纳米探针靶向效应研究

The probe integrated of diagnosis and therapy brings a new opportunity for tumor, which can realize early diagnosis, treatment and efficacy monitoring. Nanomaterials can integrate a variety of imaging contrast agents and therapeutic agents, which provide the possibility for cancer diagnosis and therapy. The melanin nanoprobe with small size has the advantage of good water-solubility and biocompatibility, strong near-infrared absorption, easy to chelate metal ions for tumor multimodality, and so on, which has excellent clinical translation prospect. However, its targeting capability is poor. We therefore propose to construct a new nanoprobe based on degradable hydroxyapatite-hybrid mesoporous silica nanoparticles (MSN/HAP) as the carrier and load MNP and then combine with RGD home peptide and Mn2+. We take advantage of the large size of MSN/HAP to improve the passive targeting of MNP cleverly. When enters into tumor intercellular substance with the weak acidic environment, the probe disintegrates into small particles, which is easier to penetrate the deep tumor tissue. The surface grafting RGD home peptide of MSN/HAP can actively target to tumor cells, which further improves the targeting effect. The new nanoprobe not only has high targeting capability, good biocompatibility and degradability, but also integrate MRI/PAI dual-mode imaging, photothermal treatment and efficacy monitoring, which will provide a new idea for tumor diagnosis and treatment.

诊疗一体化探针可同时实现早期诊断、治疗及疗效监测，为肿瘤诊疗带来新机遇。纳米材料可将多种成像对比剂和治疗剂结合于一体，从而为癌症诊疗一体化提供了可能。小尺寸黑色素纳米探针（MNP）具有水溶性和生物相容性好，近红外吸收强且易螯合金属离子进行多模态成像等优点，具有良好的临床转化前景，然而其靶向性较弱。本项目拟采用可降解羟基磷灰石杂化介孔氧化硅纳米颗粒（MSN/HAP）为载体，负载MNP，结合RGD导向肽并螯合Mn2+构建新型纳米探针。巧妙地利用MSN/HAP的大尺寸提高MNP被动靶向效应，进入肿瘤细胞间质微弱酸性环境后崩解为小颗粒，更易进入深层组织；MSN/HAP表面嫁接RGD导向肽可主动靶向肿瘤细胞，进一步提高靶向效率。这种新型纳米探针不仅具有高靶向性、良好的生物相容性和降解性，而且整合了MRI和PAI双模态成像、光热治疗和预后监测等多功能为一体，为肿瘤诊疗一体化研究提供了新思路。

诊疗一体化探针可同时实现早期诊断、治疗及疗效监测，为肿瘤诊疗带来新机遇。纳米材料可将多种成像对比剂和治疗剂结合于一体，从而为癌症诊疗一体化提供了可能。小尺寸黑色素纳米探针（MNP）具有水溶性和生物相容性好，近红外吸收强且易螯合金属离子进行多模态成像等优点，具有良好的临床转化前景，然而其靶向性较弱。本项目拟采用可降解羟基磷灰石杂化介孔氧化硅纳米颗粒（MSN/HAP）为载体，负载MNP，结合RGD导向肽并螯合Mn2+构建新型纳米探针。巧妙地利用MSN/HAP的大尺寸提高MNP被动靶向效应，进入肿瘤细胞间质微弱酸性环境后崩解为小颗粒，更易进入深层组织；MSN/HAP表面嫁接RGD导向肽可主动靶向肿瘤细胞，进一步提高靶向效率。这种新型纳米探针不仅具有高靶向性、良好的生物相容性和降解性，而且整合了MRI和PAI双模态成像、线粒体Ca2+稳态的破坏及光热协同抗肿瘤治疗、预后监测等多功能为一体，为肿瘤诊疗一体化研究提供了新思路。