RESUMEN
Currently, nano-carriers for anti-cancer drug delivery are complex systems, which struggle with immunogenicity and enhanced permeability effect (EPR)-related problems that halt the clinical translation of many therapeutics. Consequently, a rapidly growing field of research has been focusing on biomimetic nano-vesicles (BNVs) as an effective delivery alternative. Nevertheless, the translation of many BNVs is limited due to scalability problems, inconsistent production process, and insufficient loading efficiency. Here we discuss the process of our previously published BNVs, termed Nano-Ghosts (NGs), which are produced from the membrane of mesenchymal stem cells. We demonstrate the flexibility of the process, while alternating physical methodologies (sonication or extrusion) to produce the NGs while preserving their desired characteristics. We also show that our NGs can be labeled using multiple methods (fluorescence, radiolabeling, and genetic engineering) for tracking and diagnostic purposes. Lastly, we demonstrate that the loading efficiency can be improved by using electroporation to accommodate a range of therapeutics (small molecules, peptides and DNA) that can be delivered by the NGs. Our results emphasize the robustness of the NGs technology, its versatility and a vast range of applications, differentiating it from other BNVs and leading the way towards clinical translation.
Asunto(s)
Materiales Biomiméticos/química , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/química , Células A549 , Bioingeniería/métodos , Transporte Biológico , Materiales Biomiméticos/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Liberación de Fármacos , Electroporación/métodos , Vesículas Extracelulares/química , Vesículas Extracelulares/trasplante , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Mesilato de Imatinib/metabolismo , Mesilato de Imatinib/farmacología , Cinética , Células Madre Mesenquimatosas/metabolismo , Nanoestructuras/química , Péptidos/metabolismo , Péptidos/farmacología , Sonicación/métodos , Coloración y Etiquetado/métodosRESUMEN
Nanoghosts derived from mesenchymal stem cells and retaining their unique surface-associated tumor-targeting capabilities were redesigned as a selective and safe universal nonviral gene-therapy platform. pDNA-loaded nanoghosts efficiently targeted and transfected diverse cancer cells, in vitro and in vivo, in subcutaneous and metastatic orthotopic tumor models, leading to no adverse effects. Nanoghosts loaded with pDNA encoding for a cancer-toxic gene inhibited the growth of metastatic orthotopic lung cancer and subcutaneous prostate cancer models and dramatically prolonged the animals' survival.