19 February 2013 Light-activated endosomal escape using upconversion nanoparticles for enhanced delivery of drugs
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Abstract
Nanoparticle-based delivery of drugs has gained a lot of prominence recently but the main problem hampering efficient delivery of payload is the clearing or degradation of nanoparticles by endosomes. Various strategies have been used to overcome this issue and one such effective solution is Photochemical Internalization (PCI). This technique involves the activation of certain photosensitizing compounds by light, which accumulate specifically in the membranes of endocytic vesicles. The activated photosensitizers induce the formation of reactive oxygen species which in turn induces localized disruption of endosomal membranes. But the drawback of this technique is that it needs blue light for activation and hence confined to be used only in in-vitro systems due to the poor tissue penetration of blue light. Here, we report the use of Upconversion nanoparticles (UCNs) as a transducer for activation of the photosensitizer, TPPS 2a. NIR light has good tissue penetrating ability and thus enables PCI in greater depths. Highly monodisperse, uniformly-sized, sub-100 nm, biocompatible upconversion nanoparticles were synthesized with a mesoporous silica coating. These UCNs activated TPPS 2a efficiently in solution and in cells. Paclitaxel, an anti-cancer drug was used as a model drug and was loaded into the mesoporous silica coating. B16F0 cells transfected with drug-loaded UCNs and irradiated with NIR showed significantly higher nanoparticle uptake and in turn higher cell death caused by the delivered drug. This technique can be used to enhance the delivery of any therapeutic molecule and thus increase the therapeutic efficiency considerably.
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Muthu Kumara Gnanasammandhan, Muthu Kumara Gnanasammandhan, Akshaya Bansal, Akshaya Bansal, Yong Zhang, Yong Zhang, } "Light-activated endosomal escape using upconversion nanoparticles for enhanced delivery of drugs", Proc. SPIE 8594, Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications X, 85940B (19 February 2013); doi: 10.1117/12.2003720; https://doi.org/10.1117/12.2003720
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