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Biodegradable amphiphilic poly (ethylene glycol) (PEG) based ether-anhydride terpolymer, consisting of PEG, 1, 3-bis (p-carboxyphenoxy) propane (CPP) and sebacic acid (SA), namely PEG-CPP-SA terpolymer, was employed to self-assemble into micelles by adding water into a solution of the terpolymer in tetrahydrofuran (THF). The shape of polyanhydride micelles can be regulated by simply adjusting the water addition rate, where spherical, rod-like and comb-like micelles can obtained under water addition rate of 20, 3 and 1 ml/h, respectively. The effect of micellar morphologies on the cellular internalization and intracellular distribution were characterized qualitatively with cervical cancer cells (HeLa cells) and hepatoma cells (HepG2 cells) by fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry (FCM) and transmission electron microscopy (TEM). The results reveal that the cellular uptake of micelles are micelle-shape-dependent (rod-like micelles may possess the highest cellular internalization rate) and cell-type-specific. Each endocytic pathway can make a contribution to this process in different degree. Moreover, blood circulation experiments of these micelles were carried out, demonstrating that comb-like micelles have a relatively longer blood circulating feature, which may due to its irregular shape help to increase the sensitivity to fluid forces and allows them to tumble and align with the blood flow.

Polyanhydride micelles with diverse morphologies for shape-regulated cellular internalization and blood circulation