Doxorubicin-loaded polypeptide nanorods based on electrostatic interactions for cancer therapy

Zhang, Longlong; Zhang, Pei; Zhao, Qingyun; Zhang, Yongchun; Cao, Longqiao; Luan, Yuxia

doi:10.1016/j.jcis.2015.11.008

Cited by 47 publications

(17 citation statements)

References 56 publications

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“…It could be seen that there was red fluorescence in cells treated with DOX and PU·DOX nanoparticles and that the fluorescence intensity of PU·DOX nanoparticles was stronger than that of pure DOX. The results demonstrated that PU·DOX nanoparticles could enter into MCF‐7 cells by endocytosis and the cellular uptake was better than that of pure DOX, which was probably due to the different methods of cellular uptake for small molecules and nanoparticles …”

Section: Resultsmentioning

confidence: 99%

“…prepared a drug‐loaded nano‐system in water by electrostatic interactions between anionic methoxy poly(ethylene glycol)‐ b ‐poly(glutamic acid) and cationic drug doxorubicin hydrochloride (DOX·HCl) (p K a 8.3). The results showed that this system had a pH‐sensitive drug release property and excellent anticancer effects . It is therefore a good method for loading DOX by electrostatic interactions between anionic polymers and cationic drugs in the absence of organic solvents.…”

Section: Introductionmentioning

confidence: 97%

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Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

Huang

Zhou

Yuan

et al. 2018

Polymer International

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In order to obtain a pH-sensitive delivery carrier for doxorubicin (DOX), DOX-loaded polyurethane (PU·DOX) nanoparticles were readily prepared in water by electrostatic interactions between amphiphilic polyurethane with carboxyl pendent groups (PU-COOH) and doxorubicin hydrochloride (DOX·HCl). The structures of the products obtained were characterized by Fourier transform infrared spectroscopy, 1 H NMR spectroscopy, gel permeation chromatography, UV-visible spectroscopy, dynamic light scattering and transmission electron microscopy. The average hydrodynamic size of the PU·DOX nanoparticles was around 182 nm with negative surface charge (−1.1 mV) and a spherical or rodlike shape. PU·DOX nanoparticles had a higher drug-loading content of 14.1 wt%. The in vitro drug release properties of PU·DOX nanoparticles were investigated at pH 4.0, 5.0 and 7.4, respectively. PU·DOX nanoparticles exhibited a good pH-sensitive drug release property, but there was almost no release of DOX from PU·DOX nanoparticles at pH 7.4. The in vitro cellular uptake assay and the Cell Counting Kit-8 assay demonstrated that PU·DOX nanoparticles had a higher level of cellular internalization and higher inhibitory effects on the proliferation of human breast cancer (MCF-7) cells than pure DOX. The enhancement of the inhibition effects resulted from increasing apoptosis-inducing effects on MCF-7 cells, which was related to the enhancement of Bax expression and the reduction of Bcl-2 expression confirmed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay, real-time polymerase chain reaction (PCR) assay and western blot assay.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

Huang

Zhou

Yuan

et al. 2018

Polymer International

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“…sHH and PH were mixed at 4:1 ratio, forming sHH/PH nanoparticles with surface potential measuring −25.4 mV. Doxorubicin is a type of anthracycline with positively charged, which can therefore bind to the negatively charged sHH/PH nanoparticles 26 . Particle size analysis revealed that the mean size of sHH/PH/Dox was 140 ± 8 nm, and the polydispersity index (PDI) was 0.099.…”

Section: Resultsmentioning

confidence: 99%

Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres as potential multifunctional embolic agent

Hsu

Tyan

Chien

et al. 2018

Sci Rep

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The purpose of this study was to develop a gellan gum-based multifunctional embolic agent. Calibrated spherical gellan gum and nanoparticle-containing gellan gum microspheres were prepared via water-in oil emulsification method. Self-assembled nanoparticles composed of short-chain hyaluronic acid and polyethylenimine as the doxorubicin carrier were prepared. The short-chain hyaluronic acid/polyethylenimine/ doxorubicin (sHH/PH/Dox) with the mean size was 140 ± 8 nm. To examine sHH/PH/Dox nanoparticle uptake into cells, the results confirmed that sHH/PH nanoparticles as drug carrier can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, sHH/PH/Dox merged into the gellan gum (GG) microspheres forming GG/sHH/PH/Dox microsphere. After a drug release experiment lasting 45 days, the amount of released doxorubicin from 285, 388, and 481 μm GG/sHH/PH/Dox microspheres were approximately 4.8, 1.8 and 1.1-fold above the IC50 value of the HepG2 cell. GG/sHH/PH/Dox microspheres were performed in rabbit ear embolization model and ischemic necrosis on ear was visible due to the vascular after 8 days. Regarding the application of this device in the future, we aim to provide better embolization agents for transcatheter arterial chemoembolization (TACE).

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“…The high DLC and DLE of DOX‐loaded PBS‐ g ‐MPA/CS‐bi‐PEG micelles could attribute to the strong electrostatic attraction between DOX and carboxyl groups. Indeed, the carboxyl derivatives, such as poly(acrylic acid) and poly(glutamic acid), have been widely adopted to improve the DLC and DLE of delivery systems . Therefore, reducing the content of carboxyl groups leads to lower DLC and DLE of co‐assembly micelles.…”

Section: Resultsmentioning

confidence: 99%

Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

Zheng

et al. 2017

J. Polym. Sci. Part A: Polym. Chem.

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The instability and premature charge reversal at pH 7.4 have become the major limitations of charge-reversal delivery systems. To address this problem, graft copolymer of poly(butylene succinate)-g-cysteamine-bi-poly(ethylene glycol) (PBS-g-CS-bi-PEG, bi 5 benzoic imine bond) was designed and synthesized through facile thiol-ene click reaction and subsequent Schiff's base reaction. Then, PBS-g-CS-bi-PEG and carboxyl-functionalized polyester of poly(butylene succinate)-g-3-mercaptopropionic acid (PBS-g-MPA) co-assemble in aqueous solution to give PEG shell-sheddable charge-reversal micelles with sizes of 85-103 nm and low polydispersity of 0.11-0.12. Interestingly, the PBS-g-MPA/CS-bi-PEG micelles could sensitively and arbitrarily switch their surface charges between negative and positive status in response to pH fluctuation via reversible protonation and deprotonation of carboxyl and amino groups, which endows the desired stability of coassembly micelles either during long-term storage or under physiological conditions. Doxorubicin (DOX) was loaded into PBS-g-MPA/CS-bi-PEG micelles with a high drug-loading content of 10.2% and entrapment efficiency of 68% as a result of electrostatic attraction. In vitro release studies revealed that less than 25% of DOX was released within 24 h in the environment mimicking the physiological condition, whereas up to 81% of DOX was released in 24 h under weak-acid condition resembling microenvironment in endosome/lysosome. In vitro cytotoxicity study suggested that blank PBS-g-MPA/CS-bi-PEG micelles possessed excellent biocompatibility, while DOXloaded PBS-g-MPA/CS-bi-PEG micelles showed significant cytotoxicity with half-maximal inhibitory concentration (IC 50 ) of 1.55-1.67 lg DOX equiv/mL. This study provides a facile and effective approach for the preparation of novel charge-reversal micelles with switchable charges and excellent biocompatibility, which are highly promising to be used as safe nanocarriers for efficient intracellular drug delivery.

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Doxorubicin-loaded polypeptide nanorods based on electrostatic interactions for cancer therapy

Cited by 47 publications

References 56 publications

Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres as potential multifunctional embolic agent

Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

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