Abstract
ObjectivesNanocarriers can greatly enhance the cellular uptake of therapeutic agents to regulate cell proliferation and metabolism. Nevertheless, further application of nanocarriers is often limited by insufficient understanding of the mechanisms of their uptake and intracellular behaviour.Materials and methodsFluorescent polymer dots (Pdots) are coated with synthetic octaarginine peptides (R8) and are analysed for cellular uptake and intracellular transportation in HeLa cervical cancer cells via single particle tracking.ResultsSurface modification with the R8 peptide efficiently improves both cellular uptake and endosomal escape of Pdots. With single particle tracking, we capture the dynamic process of internalization and intracellular trafficking of R8‐Pdots, providing new insights into the mechanism of R8 in facilitating nanostructure‐based cellular delivery. Furthermore, our results reveal R8‐Pdots as a novel type of autophagy inducer.ConclusionsThis study provides new insights into R8‐mediated cellular uptake and endosomal escape of nanocarriers. It potentiates biological applications of Pdots in targeted cell imaging, drug delivery and gene regulation.
Highlights
Colocalization between R8‐polymer dots (Pdots) and LAMP1‐red fluorescent protein (RFP) is less than 10% after 6‐hour incubation and the ratio reaches the maximum value of 25% after 24 hours (Figure 5A,B)
We report the use of R8‐conjugated Pdots to investigate the complicated behaviour of nanoparticles in live cells, which is important for developing advanced cellular imaging probes and nanocarriers
Single particle tracking indicates that R8 modification promotes immediate binding of Pdots to negatively charged cell membranes and triggers caveolin‐dependent endocytosis, with increased amount and accelerated speed
Summary
Nanotechnology has shown great potential in biomedical applications.[1,2,3,4] Numerous nanoparticles are developed and exploited as biosensors, diagnostic imaging probes or vehicles of various therapeutic. R8‐Pdots increase autophagy levels in HeLa cells, implying that R8‐Pdots have potential to regulate cellular homeostasis directly in addition to function as imaging probes and carriers of therapeutic agents
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