Reducible self-assembled micelles for enhanced intracellular delivery of doxorubicin

Chen, Jun; Zehtabi, Fatemeh; Ouyang, Jun; Kong, Jiming; Zhong, Wen; Xing, Malcolm

doi:10.1039/c2jm15277k

Cited by 41 publications

(27 citation statements)

References 41 publications

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“…These micelles aggregated instead of disassociating after treatment with DTT for 7 days. A similar phenomenon was observed for disulfide‐containing PAE‐ graft ‐PEG (SS‐PAE‐ g ‐PEG) micelles 161. In PBS, these micelles were approximately 100 nm in size and were stable in the absence of DTT.…”

Section: Redox‐sensitive Polymeric Nanoparticlessupporting

confidence: 68%

Stimulus‐Sensitive Polymeric Nanoparticles and Their Applications as Drug and Gene Carriers

Gao

Lee

2012

Adv Healthcare Materials

141

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Polymeric nanoparticles are promising candidates as drug and gene carriers. Among polymeric nanoparticles, those that are responsive to internal or external stimuli are of greater interest because they allow more efficient delivery of therapeutics to pathological regions. Stimulus-sensitive polymeric nanoparticles have been fabricated based on numerous nanostructures, including micelles, vesicles, crosslinked nanoparticles, and hybrid nanoparticles. The changes in chemical or physical properties of polymeric nanoparticles that occur in response to single, dual, or multiple stimuli endow these nanoparticles with the ability to retain cargoes during circulation, target the pathological region, and release their cargoes after cell internalization. This Review focuses on the most recent developments in the preparation of stimulus-sensitive polymeric nanoparticles and their applications in drug and gene delivery.

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Section: Redox‐sensitive Polymeric Nanoparticlessupporting

confidence: 68%

Stimulus‐Sensitive Polymeric Nanoparticles and Their Applications as Drug and Gene Carriers

Gao

Lee

2012

Adv Healthcare Materials

141

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“…Nevertheless, micelles present the advantage of being more stable than liposomes (Andrade et al, 2011a). The versatility of micelles explains why they have been proposed as vehicles for solubilization and delivery of a variety of drugs like doxorubicin (Chen et al, 2012), paclitaxel (Kato et al, 2011;Lee et al, 2008), rifampicin (Moretton et al, 2013), calcitonin (Baginski et al, 2012), cyclosporine A (Di Tommaso et al, 2012) among others, being some formulations in clinical trials (Kato et al, 2011;Lee et al, 2008). Due to the development noted in the biotechnology field, biopharmaceuticals have emerged as an alternative to conventional drugs in the treatment of many diseases.…”

Section: Introductionmentioning

confidence: 99%

Solid state formulations composed by amphiphilic polymers for delivery of proteins: characterization and stability

Andrade

Fonte

Oliva

et al. 2015

International Journal of Pharmaceutics

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“…29,30 The work from different groups has demonstrated that reduction-responsive polymeric nanocarriers exhibit significantly improved in vitro and in vivo antitumor efficacy as compared to their reduction-insensitive counterparts. [31][32][33][34] The synthesis of reduction-responsive biocompatible and biodegradable polymeric systems, nevertheless, is not straightforward and often involves multiple steps. It should also be noted that to enhance their tumor specificity, cellular uptake and therapeutic efficacy, reduction-responsive biodegradable nanoparticles are additionally obliged to be equipped with specific targeting ligands.…”

Section: Introductionmentioning

confidence: 99%

Reductively degradable α-amino acid-based poly(ester amide)-graft-galactose copolymers: facile synthesis, self-assembly, and hepatoma-targeting doxorubicin delivery

Sun

Zou

et al. 2015

Biomater. Sci.

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Novel reductively degradable α-amino acid-based poly(ester amide)-graft-galactose (SSPEA-Gal) copolymers were designed and developed to form smart nano-vehicles for active hepatoma-targeting doxorubicin (DOX) delivery. SSPEA-Gal copolymers were readily synthesized via solution polycondensation reaction of di-p-toluenesulfonic acid salts of bis-l-phenylalanine 2,2-thiodiethanol diester and bis-vinyl sulfone functionalized cysteine hexanediol diester with dinitrophenyl ester of adipic acid, followed by conjugating with thiol-functionalized galactose (Gal-SH) via the Michael addition reaction. SSPEA-Gal formed unimodal nanoparticles (PDI = 0.10 - 0.12) in water, in which average particle sizes decreased from 138 to 91 nm with increasing Gal contents from 31.6 wt% to 42.5 wt%. Notably, in vitro drug release studies showed that over 80% DOX was released from SSPEA-Gal nanoparticles within 12 h under an intracellular mimicking reductive conditions, while low DOX release (<20%) was observed for reduction-insensitive PEA-Gal nanoparticles under otherwise the same conditions and SSPEA-Gal nanoparticles under non-reductive conditions. Notably, SSPEA-Gal nanoparticles exhibited high specificity to asialoglycoprotein receptor (ASGP-R)-overexpressing HepG2 cells. MTT assays using HepG2 cells showed that DOX-loaded SSPEA-Gal had a low half maximal inhibitory concentration (IC50) of 1.37 μg mL(-1), approaching that of free DOX. Flow cytometry and confocal laser scanning microscopy studies confirmed the efficient uptake of DOX-loaded SSPEA-Gal nanoparticles by HepG2 cells as well as fast intracellular DOX release. Importantly, SSPEA-Gal and PEA-Gal nanoparticles were non-cytotoxic to HepG2 and MCF-7 cells up to a tested concentration of 1.0 mg mL(-1). These tumor-targeting and reduction-responsive degradable nanoparticles have appeared as an interesting multi-functional platform for advanced drug delivery.

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Reducible self-assembled micelles for enhanced intracellular delivery of doxorubicin

Cited by 41 publications

References 41 publications

Stimulus‐Sensitive Polymeric Nanoparticles and Their Applications as Drug and Gene Carriers

Stimulus‐Sensitive Polymeric Nanoparticles and Their Applications as Drug and Gene Carriers

Solid state formulations composed by amphiphilic polymers for delivery of proteins: characterization and stability

Reductively degradable α-amino acid-based poly(ester amide)-graft-galactose copolymers: facile synthesis, self-assembly, and hepatoma-targeting doxorubicin delivery

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