Effects of targeting modification on intracellular transportation of PEG-PCL micelles in human cervical cancer cells
OBJECTIVE To study the effects of transferrin-targeting peptide T7(7pep)on intracellular transportation of polyethylene glycol-polycaprolactone(PEG-PCL)micelles in human cervical cancer HeLa cells.METHODS Using coumarin-6(C6)as fluorescent indicator probe,both coumarin-6(C6)-loaded PEG-PCL(PEG-PCL-C6)micelles and 7pep-modified PEG-PCL(7pep-PEG-PCL-C6)micelles were prepared by film-dispersion method.The particle size,polydispersity index and appearance morphology were compared between two types of micelles;the real-time uptake of two types of micelles by HeLa cells was compared,and the colocalization of two types of micelles with early endosomes(EE),endocytic recycling compartments(ERC)and late endosomes(LE)after entry into the cells was observed.RESULTS The particle sizes of PEG-PCL-C6 and 7pep-PEG-PCL-C6 micelles were(75.0±2.3)and(82.0±1.5)nm;the polymer dispersity indexes were 0.17±0.20 and 0.17±0.32,respectively,with a regular spherical appearance.The colocalization results showed that entry speed and amount of 7pep-PEG-PCL-C6 micelles were significantly faster/more than those of PEG-PCL-C6 micelles.7pep-PEG-PCL-C6 micelles entered EE faster than PEG-PCL-C6 micelles,while PEG-PCL-C6 micelles entered ERC at a faster rate than 7pep-PEG-PCL-C6 micelles,and both PEG-PCL-C6 micelles and 7pep-PEG-PCL-C6 micelles tended to accumulate gradually in LE;Pearson coefficient,signal overlap ratio,and colocalization ratio of 7pep-PEG-PCL-C6 micelles with LE were significantly lower 60 minutes after entering the cell than those 30 minutes after entering the cell(P＜0.05 or P＜0.01).CONCLUSIONS Targeting 7pep modification can increase the entry speed and amount of PEG-PCL-C6 micelles,and also alter their intracellular transportation behavior.
transferrin-targeting peptide T7micelletransferrin receptortargeting drug delivery systemcellular transport
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维普
