Multifunctional organic&amp;ndash;inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery

Chi, Huibo; Gu, Yan; Cao, Feng

doi:10.2147/ijn.s129311

Cited by 39 publications

(28 citation statements)

References 30 publications

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“…20 CG-GS-FITC-LDH nanocomposites exhibited no significant difference in cellular uptake in the presence of 1 and 5 mM GS compared to CG-GS-FITC-LDH nanocomposites alone. However, the internalization of different DS of GS in CG-GS-FITC-LDH nanocomposites was significantly inhibited by 10 mM GS (P,0.01).…”

mentioning

confidence: 80%

“…20 HCEpiC were incubated with endocytosis inhibitors at a certain concentration, which were not toxic to cells, ie, 2 mg/mL sodium azide, 0.45 M hypertonic sucrose, and 10 μg/mL chlorpromazine. In addition, competitive inhibitor of GS (1, 5 and 10 mM) was also investigated.…”

Section: Investigation Of Cellular Uptake Mechanismmentioning

confidence: 99%

“…42 For both CG-GS-PRN-LDH and CG-GS-LDH, a high degree of cell viability (.80%) was exhibited at the concentration range of 0-75 μg/mL after 12 h of cultivation, which was in agreement with the results of our previous study. 20 Jian et al has reported that the relatively high positive charge will not affect cellular morphology and membrane integrity. 43 Therefore, these results revealed that the nanocomposites exhibited good biocompatibility and the concentration of LDH carriers less than 75 μg/mL should be a safe level for further cellular studies.…”

Section: In Vitro Cellular Studies Cytotoxicity Assaymentioning

confidence: 99%

“…20 To further verify the mechanism involved in the uptake of CG-GS-LDH nanocomposites, cellular uptake mechanisms were investigated by utilizing endocytic inhibitors. CG-GS-FITC-LDH nanocomposites were coincubated with sodium azide for 4 h, and the fluorescence internalized into the cells was significantly reduced (P,0.001), implying an energy-dependent process was involved in the transport ( Figure S6).…”

Section: Investigation Of Cellular Uptake Mechanismmentioning

confidence: 99%

“…18 The multifunctional nanocomposites with target ligand of dipeptide VV have been demonstrated with active targeting of PepT-1 in animals and at the cellular level. 19,20 These intercalated nanocomposites with a synergistic effect between the organic and inorganic materials have received more and more attention in recent years. [21][22][23] Glycylsarcosine (GS) is one of the best known reference substrates of PepT-1 and commonly used as an inhibitor in the study of transport mechanism of PepT-1.…”

Section: Introductionmentioning

confidence: 99%

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Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

Xu¹,

Xu²,

Gu³

et al. 2018

IJN

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Background To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. Purpose The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. Materials and methods CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). Results CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. Conclusions The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site.

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mentioning

confidence: 80%

Section: Investigation Of Cellular Uptake Mechanismmentioning

confidence: 99%

Section: In Vitro Cellular Studies Cytotoxicity Assaymentioning

confidence: 99%

Section: Investigation Of Cellular Uptake Mechanismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

Xu¹,

Xu²,

Gu³

et al. 2018

IJN

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Synthesis of a Hybrid Composed of Anisotropic Niobate Layers Modified with MoC Nanoparticles

Kamibe

Yamauchi

et al. 2023

Chemistry A European J

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The hybrid composed of anisotropic niobate layers modified with MoC nanoparticles is synthesized by multistep reactions. The stepwise interlayer reactions for layered hexaniobate induce selective surface modification at the alternate interlayers, and the following ultrasonication leads to the formation of double-layered nanosheets. The further liquid phase MoC deposition with the double-layered nanosheets leads to the decoration of MoC nanoparticles on the surfaces of the double-layered nanosheets. The new hybrid can be regarded as a stacking of the two layers with anisotropically modified nanoparticles. The relatively high temperature in the MoC synthesis causes partial leaching of the grafted phosphonate groups. The exposed surface of the niobate nanosheets due to the partial leaching may interact with MoC to succeed in the hybridization. The hybrid after heating exhibits photocatalytic activity, indicating that this hybridization method can be useful for hybrid synthesis of semiconductor nanosheets and co-catalyst nanoparticles toward photocatalytic application.

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Improved mitochondrial targeting effect of HPMA copolymer by SS20 peptide mediation and nonendocytosis pathway

Liu

Xiong

et al. 2018

Journal of Peptide Science

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Mitochondrion plays an important role in executing cell programmed death pathway.Therefore, drugs designed to target mitochondria are supposed to make superior contributions to cancer therapy. However, the problem that drugs or drug delivery systems being sequestrated in endosomes/lysosomes needs to be solved for effective drug delivery. Here, mitochondrial targeting and nonendocytic cell entry peptide SS20 modified HPMA copolymer (P-FITC-SS20) was synthesized. With SS20 peptide modification, the uptake behavior of HPMA copolymers changed remarkably compared with unmodified ones. The internalization of P-FITC-SS20 was not influenced by endocytic inhibitors and temperature. Further, the internalized copolymers were not trapped in endosomes/lysosomes. Although cellular uptake of HPMA copolymer was decreased after SS20 peptide modification, SS20 peptide significantly improved mitochondrial accumulation of HPMA copolymers due to its outstanding mitochondrial targeting ability. Moreover, owing to lower susceptibility to macrophagocyte in blood, P-SS20-Cy5 showed longer blood circulation time and enhanced tumor accumulation. The current study validated that SS20 peptide modification is a promising strategy for mitochondrial targeting drug delivery systems and can be further applied to mitochondria associated diseases to improve therapeutic efficacy.

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Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery

Cited by 39 publications

References 30 publications

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

Synthesis of a Hybrid Composed of Anisotropic Niobate Layers Modified with MoC Nanoparticles

Improved mitochondrial targeting effect of HPMA copolymer by SS20 peptide mediation and nonendocytosis pathway

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