Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic block copolymer for siRNA delivery

Sun, Tianmeng; Du, Jin‐Zhi; Yan, Lifeng; Mao, Hai‐Quan; Wang, Jun

doi:10.1016/j.biomaterials.2008.07.036

Cited by 231 publications

(174 citation statements)

References 49 publications

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“…[27][28][29] As previously reported, polyphosphoesters featuring a linear molecular structure can be synthesized through the ringopening polymerization reaction of EEP in tetrahydrofuran, utilizing ROH or RNH 2 as the co-initiator, and Sn(Oct) 2 as the catalyst. 30 In this work, the PAEEP-PLLA copolymer was synthesized as illustrated in Figure 2.…”

Section: Results and Discussion Synthesis Of Paeep-plla Copolymermentioning

confidence: 88%

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

Luo¹,

Liang²,

Zhang³

et al. 2015

IJN

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In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O 1 /O 2 /W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of −12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0–20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue ® microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

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Section: Results and Discussion Synthesis Of Paeep-plla Copolymermentioning

confidence: 88%

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

Luo¹,

Liang²,

Zhang³

et al. 2015

IJN

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“…6,7 The nanosized PIC can be spontaneously formed in aqueous solution from double hydrophilic block copolymers containing ionic and nonionic blocks, upon electrostatic interaction between the ionic blocks and oppositely charged molecules such as genes, polyions, proteins, or surfactants. [8][9][10] The electrostatically neutralized ionic blocks lead to the formation of a hydrophobic core in aqueous solution, which can incorporate various pharmaceutical drugs through hydrophobic interactions and hydrogen bonding. In addition, hydrophilic and nonionic blocks such as poly(ethylene glycol) (PEG) can provide aqueous stability via steric hindrance on the surface of the particle and extended circulation times by avoiding rapid renal clearance and reticuloendothelial system uptake.…”

Section: Introductionmentioning

confidence: 99%

“…The hydrophobic PLA block in the triblock polycation was able to provide increased colloidal stability by localizing to the middle layer of PIC and enhancing cell interactions and tissue permeability of the delivery platform. 6,10,16,17 The fact is that PIC complexed with PEG-PLA-PEI and P(Asp) at various ratios of cationic PEI and anionic P(Asp) blocks (C/A ratios) shows the pH sensitivity by the protonation and deprotonation of the carboxyl groups in P(Asp) and the amine groups in the PEI blocks. pH-sensitive nanosystems could be used as a cancer reversal strategy through the exploitation of their favorable properties such as improved stability at physiological pH, reduced toxicity, and the controlled release of therapeutic agents at extracellular tumor pH (pH ex =~6.5-7.2) or endosomal pH (pH en #6.5).…”

mentioning

confidence: 99%

Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

Lim¹,

Youn²,

Lee³

et al. 2016

IJN

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A polyelectrolyte ionomer complex (PIC) composed of cationic and anionic polymers was developed for nanomedical applications. Here, a poly(ethylene glycol)–poly(lactic acid)–poly(ethylene imine) triblock copolymer (PEG–PLA–PEI) and a poly(aspartic acid) (P[Asp]) homopolymer were synthesized. These polyelectrolytes formed stable aggregates through electrostatic interactions between the cationic PEI and the anionic P(Asp) blocks. In particular, the addition of a hydrophobic PLA and a hydrophilic PEG to triblock copolyelectrolytes provided colloidal aggregation stability by forming a tight hydrophobic core and steric hindrance on the surface of PIC, respectively. The PIC showed different particle sizes and zeta potentials depending on the ratio of cationic PEI and anionic P(Asp) blocks (C/A ratio). The doxorubicin (dox)-loaded PIC, prepared with a C/A ratio of 8, demonstrated pH-dependent behavior by the deprotonation/protonation of polyelectrolyte blocks. The drug release and the cytotoxicity of the dox-loaded PIC (C/A ratio: 8) increased under acidic conditions compared with physiological pH, due to the destabilization of the formation of the electrostatic core. In vivo animal imaging revealed that the prepared PIC accumulated at the targeted tumor site for 24 hours. Therefore, the prepared pH-sensitive PIC could have considerable potential as a nanomedicinal platform for anticancer therapy.

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“…These functions improve bioavailability and decrease the risk of side effects. 17 In the past decade, polyethylene glycol-poly ε-caprolactone (PEG-PCL) micelles have been reported to feature a selfassembled core-shell structure in nanoscale. PEG is a biocompatible water-soluble polymer without immunogenicity, and is widely used in designing amphiphilic block copolymers.…”

Section: Introductionmentioning

confidence: 99%

Self-assembled mPEG–PCL-g–PEI micelles for simultaneous codelivery of chemotherapeutic drugs and DNA: synthesis and characterization in vitro

Qian¹

2012

IJN

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Background:In this paper, a series of amphiphilic triblock copolymers based on polyethylene glycol-poly ε-caprolactone-polyethylenimine (mPEG-PCL-g-PEI) were successfully synthesized, and their application for codelivery of chemotherapeutic drugs and DNA simultaneously was investigated. Methods and results: These copolymers could self-assemble into micelles with positive charges. The size and zeta potential of the micelles was measured, and the results indicate that temperature had a large effect on the micelles obtained. In vitro gene transfection evaluation in cancer cells indicated that the self-assembled micelles could serve as potential gene delivery vectors. In addition, hydrophobic drug entrapment efficiency and codelivery with the gene was also studied in vitro. The self-assembled micelles could load doxorubicin efficiently and increase cellular uptake in vitro, while maintaining high gene transfection efficiency. Conclusion:The triblock copolymer mPEG-PCL-g-PEI could be a novel vector for codelivery of drug and gene therapy.

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Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic block copolymer for siRNA delivery

Cited by 231 publications

References 49 publications

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

Self-assembled mPEG–PCL-g–PEI micelles for simultaneous codelivery of chemotherapeutic drugs and DNA: synthesis and characterization in vitro

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Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic block copolymer for siRNA delivery

Cited by 231 publications

References 49 publications

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

Self-assembled mPEG&ndash;PCL-g&ndash;PEI micelles for simultaneous codelivery of chemotherapeutic drugs and DNA: synthesis and characterization in vitro

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Self-assembled mPEG–PCL-g–PEI micelles for simultaneous codelivery of chemotherapeutic drugs and DNA: synthesis and characterization in vitro