Khorenko Mikhail, Pfeifer Juliana, Napp Joanna, Meschkov Anna, Alves Frauke, Schepers Ute, Feldmann Claus
Institute of Inorganic Chemistry, Karlsruhe Institute of Technology (KIT), Engesserstraße 15, 76131 Karlsruhe, Germany.
Institute of Functional Interfaces, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
J Mater Chem B. 2023 Apr 26;11(16):3635-3649. doi: 10.1039/d3tb00226h.
Theranostic inorganic-organic hybrid nanoparticles (IOH-NPs) with a cocktail of chemotherapeutic and cytostatic drugs and a composition Gd[(PMX)(EMP)], [Gd(OH)][(PMX)(AlPCS)], or [Gd(OH)][(PMX)(TPPS)] (PMX: pemetrexed, EMP: estramustine phosphate, AlPCS: aluminum(III) chlorido phthalocyanine tetrasulfonate, TPPS: tetraphenylporphine sulfonate) are presented for the first time. These IOH-NPs are prepared in water (40-60 nm in size) and have a non-complex composition with outstanding drug loading (71-82% of total nanoparticle mass) of at least two chemotherapeutic or a mixture of cytostatic and photosensitizing agents. All IOH-NPs show red to deep-red emission (650-800 nm) to enable optical imaging. The superior performance of the IOH-NPs with a chemotherapeutic/cytostatic cocktail is validated based on cell-viability assays and angiogenesis studies with human umbilical vein endothelial cells (HUVEC). The synergistic anti-cancer effect of the IOH-NPs with a chemotherapeutic cocktail is shown in a murine breast-cancer cell line (pH8N8) and a human pancreatic cancer cell line (AsPC1), whereas the synergistic cytotoxic and phototoxic efficacy is verified in response to illumination of HeLa-GFP cancer cells, MTT assays with human colon cancer cells (HCT116), and normal human dermal fibroblasts (NHDF). HepG2 spheroids as 3D cell cultures prove the effective uptake of the IOH-NPs with high uniform distribution and the release of the chemotherapeutic drugs with the strong synergistic effect of the cocktail of drugs.
首次展示了具有化疗和细胞抑制药物组合以及组成成分为Gd[(PMX)(EMP)]、[Gd(OH)][(PMX)(AlPCS)]或[Gd(OH)][(PMX)(TPPS)]（PMX：培美曲塞，EMP：磷酸雌莫司汀，AlPCS：四磺酸铝酞菁，TPPS：四苯基卟啉磺酸盐）的治疗诊断用无机-有机杂化纳米颗粒（IOH-NPs）。这些IOH-NPs在水中制备（尺寸为40-60纳米），具有简单的组成，对至少两种化疗药物或细胞抑制与光敏剂混合物具有出色的载药量（占纳米颗粒总质量的71-82%）。所有IOH-NPs均呈现红色至深红色发射（650-800纳米），以实现光学成像。基于对人脐静脉内皮细胞（HUVEC）的细胞活力测定和血管生成研究，验证了具有化疗/细胞抑制药物组合的IOH-NPs的卓越性能。在小鼠乳腺癌细胞系（pH8N8）和人胰腺癌细胞系（AsPC1）中显示了具有化疗药物组合的IOH-NPs的协同抗癌作用，而在HeLa-GFP癌细胞光照、人结肠癌细胞（HCT116）和正常人皮肤成纤维细胞（NHDF）的MTT测定中验证了协同细胞毒性和光毒性功效。作为三维细胞培养的HepG2球体证明了IOH-NPs的有效摄取，具有高度均匀的分布以及化疗药物的释放，且药物组合具有强大的协同作用。
