ABSTRACT
The regulation of the cell cycle has recently opened up a new research perspective for cancer treatment. So far, no effort has been made for temporal control of cell cycles using a photocleavable linker. Presented herein is the first report of regulation of disrupted cell cycles through the temporal release of a well-known cell cycle regulator α-lipoic acid (ALA), enabled by a newly designed NIR-active quinoxaline-based photoremovable protecting group (PRPG). The suitable quinoxaline-based photocage of ALA (tetraphenylethelene conjugated) has been formulated as fluorescent organic nanoparticles (FONs) and used effectively as a nano-DDS (drug delivery system) for better solubility and cellular internalization. Fascinatingly, the enhanced TP (two-photon) absorption cross section of the nano-DDS (503 GM) signifies its utility for biological applications. Using green light, we have successfully controlled the time span of cell cycles and cell growth of skin melanoma cell lines (B16F10) by the temporal release of ALA. Further, in silico studies and PDH activity assay supported the observed regulatory behavior of our nano-DDS with respect to photoirradiation. Overall, this approach expands the research path toward a futuristic photocontrolled toolbox for cell cycle regulation.
Subject(s)
Nanoparticles , Prodrugs , Thioctic Acid , Nanoparticle Drug Delivery System , Quinoxalines/pharmacology , Drug Delivery Systems/methods , Cell CycleABSTRACT
In this study a major lectin called Concanavalin A (ConA) has been micropatterned on a glass substrate by microcontact printing and the patterns have been characterized with fluorescent and atomic force microscope for their uniformity. Interaction of the patterns with mammalian cells has been investigated by culturing L929 mouse fibroblast cells on the ConA printed glass surface. Cell culture results obtained from the microcontact printed patterns have also been compared and benchmarked with another patterning technique named micromolding in capillaries (MIMIC). It has been revealed that in spite of molecular level heterogeneity and agglomeration of protein molecules in microcontact printed form, they can still interact with cell surface glycoproteins, impede the mobility of membrane receptor which results in altered morphology of the fibroblast cells.