title: Polymersomes from dual responsive block copolymers: drug encapsulation by heating and acid-triggered release.
abstract: A series of well-defined thermoresponsive diblock copolymers (PEO45-b-PtNEAn, n=22, 44, 63, 91, 172) were prepared by the atom transfer radical polymerization of trans-N-(2-ethoxy-1,3-dioxan-5-yl) acrylamide (tNEA) using a poly(ethylene oxide) (PEO45) macroinitiator. All copolymers are water-soluble at low temperature, but upon quickly heating to 37 °C, laser light scattering (LLS) and transmission electron microscopy (TEM) characterizations indicate that these copolymers self-assemble into aggregates with different morphologies depending on the chain length of PtNEA and the polymer concentration; the morphologies gradually evolved from spherical solid nanoparticles to a polymersome as the degree of polymerization ("n") of PtNEA block increased from 22 to 172, with the formation of clusters with rod-like structure at the intermediate PtNEA length. Both the spherical nanoparticle and the polymersome are stable at physiological pH but susceptible to the mildly acidic medium. Acid-triggered hydrolysis behaviors of the aggregates were investigated by LLS, Nile red fluorescence, TEM, and (1)H NMR spectroscopy. The results revealed that the spherical nanoparticles formed from PEO45-b-PtNEA44 dissociated faster than the polymersomes of PEO45-b-PtNEA172, and both aggregates showed an enhanced hydrolysis under acidic conditions. Both the spherical nanoparticle and polymersome are able to efficiently load the hydrophobic doxorubicin (DOX), and water-soluble fluorescein isothiocyanate-lysozyme (FITC-Lys) can be conveniently encapsulated into the polymersome without using any organic solvent. Moreover, FITC-Lys and DOX could be coloaded in the polymersome. The drugs loaded either in the polymersome or in the spherical nanoparticle could be released by acid triggering. Finally, the DOX-loaded assemblies display concentration-dependent cytotoxicity to HepG2 cells, while the copolymers themselves are nontoxic.
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Polymer Chemistry & Physics of Ministry of Education, Department of Polymer Science & Engineering, College of Chemistry & Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Zeng-Ying
authors.initials: ZY
authors.lastname: Qiao
authors.forename: Ran
authors.initials: R
authors.lastname: Ji
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Huang
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Du
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: De-Hai
authors.initials: DH
authors.lastname: Liang
authors.forename: Zi-Chen
authors.initials: ZC
authors.lastname: Li
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D004339:Drug Compounding; D016650:Fluorescein-5-isothiocyanate; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D009113:Muramidase; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin; D009113:Muramidase; D016650:Fluorescein-5-isothiocyanate