Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

Yu, Junhua; Xie, Xin; Zheng, Minghui; Yu, Ling; Zhang, Lei; Zhao, Jinmin; Jiang, Dengzhao; Che, Xiangxin

doi:10.2147/ijn.s36150

Cited by 45 publications

(31 citation statements)

References 47 publications

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“…The endocytosis of nanoparticles, a common route for cellular uptake, is usually slower than the passive transport by which free DOX enters cells. 39 Clearly, at least 4 hours is required to initiate significant endocytosis of the DOX-loaded nanoparticles in this study.…”

Section: Cellular Uptake and Endocytotic Mechanismmentioning

confidence: 91%

Self-Assembled Monomethoxy (Polyethylene Glycol)-b-P(D,L-Lactic-co-Glycolic Acid)-b-P(L-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered Release of Doxorubicin

Xu¹,

Cai²,

Gou³

et al. 2015

j biomed nanotechnol

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Triblock copolymers, Monomethoxy (Polyethylene glycol)-b-P(D,L-lactic-co-glycolic acid)-b-P(L-glutamic acid) (mPEG-PLGA-PGlu) with different molecular weights, were synthesized and mPEG(5k)-PLGA(20.5k)-PGlu(7.9k) were self-assembled into negatively charged nanoparticles with a hybrid core of PLGA and PGlu, and a stealth PEG shell. Because of electrostatic interaction with the negative hybrid-core, the model drug, doxorubicin (DOX), could be easily loaded into the hybrid-core nanoparticles with a high drug loading of ca. 25%. The hydrophobic interaction provided by PLGA could increase the stability of drug-loaded nanoparticles with no change in particle size for at least 3 days and only minor drug leakage (< 0.5%) in pH7.4 physiological media. Due to protonation of PGlu block in pH5.0 medium, the hybrid-core of these nanoparticles was destroyed, as shown by transmission electron microscopy, and this resulted in an increase in the pH-triggered release of DOX from 38.9% in pH7.4 release medium to 71% in pH5.0 release medium at 24 h. In vitro cytotoxicity testing involving MCF-7 and NCI-H460 cells showed that DOX-loaded nanoparticles were more cytotoxic to both types of cells than free DOX. Time-dependent cellular uptake of the drug-loaded nanoparticles was observed and at least 4 hours was required for rapid internalization through caveolinmediated endocytosis and macropinocytosis by MCF-7 cells into the endosomes where pH-trigged release of DOX from the nanoparticles occurred. The hybrid-core nanoparticles represent a potentially useful therapeutic delivery system for cationic drugs due to their high drug loading, high stability in physiological media and intracellular pH-triggered release.

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Section: Cellular Uptake and Endocytotic Mechanismmentioning

confidence: 91%

Self-Assembled Monomethoxy (Polyethylene Glycol)-b-P(D,L-Lactic-co-Glycolic Acid)-b-P(L-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered Release of Doxorubicin

Xu¹,

Cai²,

Gou³

et al. 2015

j biomed nanotechnol

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“…Notably, the fluorescence intensity of DOX/GA-GEL-2 micelles was equivalent to DOX⋅HCl in 6 h ( Figure 6(b)). As previously reported, drug-loaded micelles were transported into the cells by an energy-dependent endocytosis way, and DOX⋅HCl could quickly enter the cells by a passive diffusion manner [38]. The drug-loaded micelles were entered into tumor cells in a slow way.…”

Section: In Vitro Cellularmentioning

confidence: 61%

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Fan

Yan

et al. 2018

Journal of Nanomaterials

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Hepatocellular carcinoma (HCC) is one of the most prevalent fatal diseases and the incidence of HCC is increasing worldwide. Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in HCC therapy. Herein, novel glycyrrhetinic acid modified gelatin (GA-GEL) conjugates with three substitution degrees were synthesized and characterized. Doxorubicin (DOX) was applied as a model drug. DOX-loaded GA-GEL (DOX/GA-GEL) micelles were prepared by an emulsionsolvent evaporation method. The mean diameters of DOX/GA-GEL micelles were in the range of 195-235 nm. The encapsulation efficiency of DOX/GA-GEL micelles was 63.6%-96.2%, and the loading content was 8.3%-12.5%. Drug release from DOX-loaded micelles exhibited a biphasic manner in phosphate buffer solution (PBS) at pH 7.4. DOX/GA-GEL could be efficiently accumulated into human liver cancer HepG2 cells. The IC 50 values of DOX/GA-GEL-2 and DOX⋅HCl in HepG2 cells were 0.33 and 0.66 g/mL, respectively. In vivo imaging analysis demonstrated that the fluorescence signals of DiR-labeled GA-GEL-2 micelles were mainly distributed in liver and H22 orthotopic tumor, indicating that GA-GEL had the liver-targeting activity. Compared to DOX⋅HCl, DOX/GA-GEL-2 exhibited better antitumor activity in H22 orthotopic mice. Therefore, these results indicated that GA-GEL could be used as carrier of hydrophobic drug for targeting HCC.

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“…Cholesterol-modified glycol chitosan (CHGC) was synthesized according to the previously reported procedure [18,22] …”

Section: Synthesis Of Bio-chgc Conjugatementioning

confidence: 99%

Collagen/chitosan film containing biotinylated glycol chitosan nanoparticles for localized drug delivery

Chen

Huang

Cao

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

Cited by 45 publications

References 47 publications

Self-Assembled Monomethoxy (Polyethylene Glycol)-<I>b</I>-<I>P</I>(<I>D</I>,<I>L</I>-Lactic-<I>co</I>-Glycolic Acid)-<I>b</I>-<I>P</I>(<I>L</I>-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered Release of Doxorubicin

Self-Assembled Monomethoxy (Polyethylene Glycol)-<I>b</I>-<I>P</I>(<I>D</I>,<I>L</I>-Lactic-<I>co</I>-Glycolic Acid)-<I>b</I>-<I>P</I>(<I>L</I>-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered Release of Doxorubicin

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Collagen/chitosan film containing biotinylated glycol chitosan nanoparticles for localized drug delivery

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