Abstract
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.
Highlights
Scientists have long been working on finding effective ways to improve systemic chemotherapy for cancers to be more efficient and safety
The shape of polyanhydride micelles can be regulated by 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 results reveal that the cellular uptake of micelles are micelle-shape-dependent and cell-type-specific
Summary
Scientists have long been working on finding effective ways to improve systemic chemotherapy for cancers to be more efficient and safety. Efforts have been made to redesign these nanocarrirers to remedy this situation, such as optimizing the nanoparticle size [4, 5], modifying the surface chemistry of nanoparticle [6], functionalizing the nanocarriers [7,8,9,10] and regulating the shape of nanoparticles [6, 11, 12] Among those strategies, regulating the shapes or geometries of the nanocarriers was emerging as a promising strategy to understand the internalization process and enhance the cellular internalization, prolong blood circulation and improve the biodistribution of nanoparticles [13,14,15].
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