Rationally integrating peptide-induced targeting and multimodal therapies in a dual-shell theranostic platform for orthotopic metastatic spinal tumors
Rationally integrating peptide-induced targeting and multimodal therapies in a dual-shell theranostic platform for orthotopic metastatic spinal tumors
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DOI：
10.1016/j.biomaterials.2021.120917
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发表时间：
2021-06-26
期刊：
影响因子：
14
通讯作者：
Dong, Jian
中科院分区：
文献类型：
--
作者：
Ma, Yiqun;Chen, Liang;Dong, Jian
转移性肿瘤给诊断和治疗带来了巨大的挑战。在此，开发了一种由金纳米粒子核和金属有机框架（MOF）和介孔二氧化硅（MS）双壳组成的概念验证治疗诊断纳米平台，用于在原位模型中对抗肺癌脊柱转移。抑制剂Alpelisib（BYL719）和化疗药物顺铂两种药物分别负载于高负载量的双壳中。最外层的 MS 层上缀合了一种名为 dYNH 的靶向肽和吲哚菁绿 (ICG)，用于特异性靶向转移性肿瘤细胞并增强光热效应。荧光和光声成像证明，所得的 Au@MOF@MS-ICG -dYNH-PAA (AMMD) 显示肿瘤细胞的细胞摄取增强以及转移性脊柱肿瘤的积累。得益于对肿瘤细胞的超高亲和力以及ICG的光热效应，ICG修饰的双载药AMMD（BCAMMD）对脊柱肿瘤表现出优异的治疗效果。更重要的是，BCAMMD 中的 BYL719 可以有效抑制骨相关肿瘤中经常发生的骨破坏。因此，通过合理地整合多种功能，包括优异的靶向能力、双药物负载、光热治疗和光声成像，所开发的一体化治疗诊断纳米平台为利用纳米医学有效治疗转移性脊柱肿瘤提供了有用的范例。
Metastatic tumors present great challenges in diagnosis and treatment. Herein, a proof-of-concept theranostic nanoplatform composed of an Au nanoparticle core and a double-shell of metal-organic framework (MOF) and mesoporous silica (MS) is developed for combating spinal metastasis of lung cancer in an orthotopic model. Two drugs, Alpelisib (BYL719) as an inhibitor and cisplatin as a chemotherapeutic drug, are separately loaded into the double-shell with high loading content. A targeting peptide called dYNH and indocyanine green (ICG) are conjugated onto the outmost MS layer for specifically targeting metastatic tumor cells and enhancing photothermal effect. The resultant Au@MOF@MS-ICG -dYNH-PAA (AMMD) shows enhanced cellular uptake on tumor cells and accumulation at metastatic spinal tumors, as evidenced by fluorescent and photoacoustic imaging. Benefiting from this ultra-high affinity to tumor cells and the photothermal effect of ICG, the dual-drug-loaded AMMD (BCAMMD) modified with ICG exhibits superior therapeutic efficacy on spinal tumors. More importantly, bone destruction, which frequently occurs in bone-related tumors, is effectively suppressed by BYL719 in BCAMMD. Hence, by rationally integrating multiple functions, including excellent targeting ability, dual-drug loading, photothermal therapy, and photoacoustic imaging, the developed all-in-one theranostic nanoplatform provides a useful paradigm of employing nanomedicine to treat metastatic spinal tumors efficiently.