2011
DOI: 10.1021/la203843m
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pH and Reduction Dual-Bioresponsive Polymersomes for Efficient Intracellular Protein Delivery

Abstract: pH and reduction dual-bioresponsive nanosized polymersomes based on poly(ethylene glycol)-SS-poly(2-(diethyl amino)ethyl methacrylate) (PEG-SS-PDEA) diblock copolymers were developed for efficient encapsulation and triggered intracellular release of proteins. PEG-SS-PDEA copolymers with PDEA-block molecular weights ranging from 4.7, 6.8, to 9.2 kg/mol were synthesized in a controlled manner via reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(diethyl amino)ethyl methacrylate (DEAEMA… Show more

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Cited by 123 publications
(95 citation statements)
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“…PMs are generally formed by supramolecular assemblies of amphi- [71] mPEG-SS-PzLL DPA 302 -DOX MCF-7 cells [72] mPEG-SS-Pleu Cystamine dihydrochloride 160 -DOX HepG2 cells [73] PEG-SS-PBLG Cystamine dihydrochloride 137 -DOX SCC7 cells [54] PEG-SS-PBLG Cystamine dihydrochloride 107 -SN-38 L929 cells [56] PEG-SS-PLys-PLeu Cystamine dihydrochloride 150 -3.52 CPT HeLa cells [22] Vesicles PEG-b-PLys(Z)-SS-PCL SPDP 256 43.9 ± 1.61 DOX·HCl; CPT SCC7 cells [66] PzLL-SS-PEG-SS-PzLL Cystamine dihydrochloride 380 -DOX·HCl; GC·HCl MDA-MB-231 cells [26] PEG-SS-PCL 2,2′-dithiodipyridine 210.0 0.40 ± 0.2 Cytochrome C (CC) proteins; recombinant human granzyme B MCF-7 cells, HepG2 cells [44] PEG-SS-PDEA Cystamine dihydrochloride 54.5−66.8 -FITC-BSA; FITC-CC MCF-7 cells [74] Prodrug system (MTX) 2 PEG(MTX) 2 Cystamine dihydrochloride 278 -MTX HepG2 cells [25] CPT-SS-PEG-SS-CPT Cystamine dihydrochloride 226 -CPT HepG2 cells [45] P(PTX-DTPA-HEMA)-co-PPEGMEA DPA 135 -PTX HEK-293 cells; HeLa cells [75] Organicinorganic nanocomposite NGO-SS-mPEG Cysteamine hydrochloride 220 -DOX·HCl HeLa cells [76] MSNs-SS-mPEG mPEG-SS-Pyridine 100 -27.8 Fluorescein dye MCF-7 cells [24] S-P-βCD; S-T-βCD; S-MT-βCD SPDP; SPT; SMPT <100 -Rhodamine B dye Zebrafish (Danio rerio) [77] Gene vector mPEG-SS-Lys n -r-His m Cystamine dihydrochloride Disulfide-bridged cleavable PEGylation in polymeric nanomedicine for controlled therapeutic delivery Review philic polymers that possess unique core-shell structure. The inner core can be an efficient reservoir for drug encapsulation, which is protected by the hydrophilic shell, a necessary interface between the core and the external environment.…”
Section: Polymeric Micellesmentioning
confidence: 99%
“…PMs are generally formed by supramolecular assemblies of amphi- [71] mPEG-SS-PzLL DPA 302 -DOX MCF-7 cells [72] mPEG-SS-Pleu Cystamine dihydrochloride 160 -DOX HepG2 cells [73] PEG-SS-PBLG Cystamine dihydrochloride 137 -DOX SCC7 cells [54] PEG-SS-PBLG Cystamine dihydrochloride 107 -SN-38 L929 cells [56] PEG-SS-PLys-PLeu Cystamine dihydrochloride 150 -3.52 CPT HeLa cells [22] Vesicles PEG-b-PLys(Z)-SS-PCL SPDP 256 43.9 ± 1.61 DOX·HCl; CPT SCC7 cells [66] PzLL-SS-PEG-SS-PzLL Cystamine dihydrochloride 380 -DOX·HCl; GC·HCl MDA-MB-231 cells [26] PEG-SS-PCL 2,2′-dithiodipyridine 210.0 0.40 ± 0.2 Cytochrome C (CC) proteins; recombinant human granzyme B MCF-7 cells, HepG2 cells [44] PEG-SS-PDEA Cystamine dihydrochloride 54.5−66.8 -FITC-BSA; FITC-CC MCF-7 cells [74] Prodrug system (MTX) 2 PEG(MTX) 2 Cystamine dihydrochloride 278 -MTX HepG2 cells [25] CPT-SS-PEG-SS-CPT Cystamine dihydrochloride 226 -CPT HepG2 cells [45] P(PTX-DTPA-HEMA)-co-PPEGMEA DPA 135 -PTX HEK-293 cells; HeLa cells [75] Organicinorganic nanocomposite NGO-SS-mPEG Cysteamine hydrochloride 220 -DOX·HCl HeLa cells [76] MSNs-SS-mPEG mPEG-SS-Pyridine 100 -27.8 Fluorescein dye MCF-7 cells [24] S-P-βCD; S-T-βCD; S-MT-βCD SPDP; SPT; SMPT <100 -Rhodamine B dye Zebrafish (Danio rerio) [77] Gene vector mPEG-SS-Lys n -r-His m Cystamine dihydrochloride Disulfide-bridged cleavable PEGylation in polymeric nanomedicine for controlled therapeutic delivery Review philic polymers that possess unique core-shell structure. The inner core can be an efficient reservoir for drug encapsulation, which is protected by the hydrophilic shell, a necessary interface between the core and the external environment.…”
Section: Polymeric Micellesmentioning
confidence: 99%
“…Cell experiments demonstrated that the intracellular protein release and therefore cell apoptosis effect of cytochrome C (CC)-loaded chimeric polymersomes were closely related to the disulfide content. The reduction and pH dual-sensitive PEG-SS-PDEA polymersomes, although stable with minimal protein release under physiological conditions, rapidly dissolved or formed large aggregates in response to endosomal pH and/or intracellular-mimicking reductive environment, affording fast protein release (95). CC-loaded dual-sensitive polymersomes have demonstrated much faster release of CC inside the MCF-7 cells and significantly enhanced apoptosis (42.9% in 48 h with CC dosage of 80 lg/ml) compared to free CC and CC-loaded reductioninsensitive PEG-b-PDEA control (18.3% and 29.1% apoptosis, respectively).…”
Section: Reduction-sensitive Shell-sheddable Micelles and Polymersomesmentioning
confidence: 99%
“…16 In general, molecules larger than 5 nm in diameter do not readily cross the capillary endothelium and will remain in the circulation until they are cleared from the body. 17 However, certain tissues, including the liver, spleen, and some tumors allow passage of molecules up to 200 nm in diameter which can accommodate a typical drug delivery nanoparticle. 18 The size distribution of the nanoparticles was examined using a particle size and shape analyzer (CIS-100; Ankersmid).…”
Section: In Vitro Cytotoxicitymentioning
confidence: 99%