Currently, major concerns about the safety and efficacy of RNA interference (RNAi)-based bone anabolic strategies still exist because of the lack of direct osteoblast-specific delivery systems for ...osteogenic siRNAs. Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteoblasts, and then we developed CH6 aptamer-functionalized lipid nanoparticles (LNPs) encapsulating osteogenic pleckstrin homology domain-containing family O member 1 (Plekho1) siRNA (CH6-LNPs-siRNA). Our results showed that CH6 facilitated in vitro osteoblast-selective uptake of Plekho1 siRNA, mainly via macropinocytosis, and boosted in vivo osteoblast-specific Plekho1 gene silencing, which promoted bone formation, improved bone microarchitecture, increased bone mass and enhanced mechanical properties in both osteopenic and healthy rodents. These results indicate that osteoblast-specific aptamer-functionalized LNPs could act as a new RNAi-based bone anabolic strategy, advancing the targeted delivery selectivity of osteogenic siRNAs from the tissue level to the cellular level.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Lack of effective photosensitizers has become a major limit for extensive application of photodynamic therapy. In this study, the photocytotoxicity and mode of death induced by a newly developed ...photosensitizer MPPa, a derivative of chlorophyll a, were investigated in PC-3M cell line, a highly metastatic variant of poorly differentiated androgen-independent proctanec adenocarcinoma PC-3. MTT reduction assay was used to measure cytotoxicity in both PC-3M and HUVEC, after which a flow cytometer was used to measure apoptotic rate and cell cycle, and then Caspase-3, -8, -9 were investigated. Finally, an animal model was set up to embody the curative effect and for histopathological examinations. The photocytotoxicity of MPPa showed both light- and drug-dose dependent characteristics and no significant dark cytotoxicity was observed in PC-3M cells. In HUVEC, MPPa exhibited an obviously low cytotoxicity. By other in vitro studies, we found MPPa–PDT induced apoptotic mainly via the mitochondrial/Caspase-9/Caspase-3 pathway and could restrain the cell cycle progression from the more sensitive G
0/G
1-phases. In vivo, the tumour growth was significantly inhibited after PDT, and many apoptotic cells could be seen by histopathological examinations. These results indicate the death way of cells induced by MPPa is mainly via mild apoptotic and the cure effect is obvious, suggesting that MPPa is a potential photosensitizer of photodynamic therapy for prostate cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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