DTX-loaded star-shaped TAPP-PLA-b-TPGS nanoparticles for cancer chemical and photodynamic combination therapy

Wang, Teng; Zhu, Dunwan; Liu, Gan; Tao, Wei; Cao, Wei; Zhang, Linhua; Wang, Lijun; Chen, Hongbo; Mei, Lin; Huang, Laiqiang; Zeng, Xiaowei

doi:10.1039/c5ra09042c

Cited by 31 publications

(17 citation statements)

References 49 publications

(71 reference statements)

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“…7-a. Consistent with previous results [57][58][59], cells treated with SLN-DTX or DTX resulted in an arrest in the phase of G2-M, with a significant decrease in G0/G1 phase versus control cells. The accumulation in G2-M phase was significantly higher in cells treated with SLN-DTX (73.7%) than in cells treated with free DTX (67.8%), suggesting that DTX was released into the cytosol, which caused cell cycle arrest in the G2-M phase.…”

Section: Cell Cycle Analysis and Cell Apoptosissupporting

confidence: 92%

“…Therefore, the induction of cell cycle arrest may be a good and effective strategy to control aberrant cancer cell proliferation [56]. Docetaxel has been shown to induce microtubule damage, which results in prolonged G2-M arrest and subsequent apoptosis [57]. Cell cycle analysis of 4T1 cells exposed to SLN-DTX or DTX is shown in Fig.…”

Section: Cell Cycle Analysis and Cell Apoptosismentioning

confidence: 99%

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Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

et al. 2020

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Background: Metastasis causes the most breast cancer-related deaths in women. Here, we investigated the antitumor effect of solid lipid nanoparticles (SLN-DTX) when used in the treatment of metastatic breast tumors using 4T1-bearing BALB/c mice. Results: Solid lipid nanoparticles (SLNs) were produced using the high-energy method. Compritol 888 ATO was selected as the lipid matrix, and Pluronic F127 and Span 80 as the surfactants to stabilize nanoparticle dispersion. The particles had high stability for at least 120 days. The SLNs' dispersion size was 128 nm, their polydispersity index (PDI) was 0.2, and they showed a negative zeta potential. SLNs had high docetaxel (DTX) entrapment efficiency (86%), 2% of drug loading and showed a controlled drug-release profile. The half-maximal inhibitory concentration (IC 50) of SLN-DTX against 4T1 cells was more than 100 times lower than that of free DTX after 24 h treatment. In the cellular uptake test, SLN-DTX was taken into the cells significantly more than free DTX. The accumulation in the G2-M phase was significantly higher in cells treated with SLN-DTX (73.7%) than in cells treated with free DTX (23.0%), which induced subsequent apoptosis. TEM analysis revealed that SLN-DTX internalization is mediated by endocytosis, and fluorescence microscopy showed DTX induced microtubule damage. In vivo studies showed that SLN-DTX compared to free docetaxel exhibited higher antitumor efficacy by reducing tumor volume (p < 0.0001) and also prevented spontaneous lung metastasis in 4T1 tumor-bearing mice. Histological studies of lungs confirmed that treatment with SLN-DTX was able to prevent tumor. IL-6 serum levels, ki-67 and BCL-2 expression were analyzed and showed a remarkably strong reduction when used in a combined treatment. Conclusions: These results indicate that DTX-loaded SLNs may be a promising carrier to treat breast cancer and in metastasis prevention.

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Section: Cell Cycle Analysis and Cell Apoptosissupporting

confidence: 92%

Section: Cell Cycle Analysis and Cell Apoptosismentioning

confidence: 99%

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

et al. 2020

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“…The enhanced effect of these NPs could be attributed to the strong electrostatic interactions between positively charged CS and the negative glycocalyx on the cell membrane [7,[63][64][65][66][67][68]. This effect increased NPs-cell membrane interactions, which facilitate the anticancer activity.…”

Section: In Vitro Cytotoxicitymentioning

confidence: 99%

RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

Ahmad

Alam

Naqvi

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Docetaxel (DTX), a cytotoxic taxane, is a poor water-soluble drug and exhibits less oral bioavailability. Current research investigates the effective transport, for DTX-loaded chitosan (CS)-coated-poly-lactide-co-glycolide (PLGA)-nanoparticles (NPs) (DTX-CS-PLGA-NPs) and DTX-PLGA-NPs as well as a novel third-generation P-gp inhibitor i.e. GF120918 (Elacridar), across intestinal epithelium with its successive uptake by the tumour cells in an in vitro model. The prepared NPs showed a spherical shape particle size i.e. <123.96 nm with polydispersity index (PDI) of <0.290 whereas for CS-coated NPs, the zeta potential was converted from negative to positive value along with a small modification in particle size distribution. The entrapment efficiency observed for DTX-CS-PLGA-NPs was 74.77%, whereas the in vitro release profile revealed an initial rapid DTX release followed by a sustained release pattern. For apparent permeability, DTX-CS-PLGA-NPs and DTX-PLGA-NPs along with GF120918 showed a five-fold (p < .01) and 2.2-fold enhancement, respectively, as observed in rat ileum permeation study. Similarly, for pharmacokinetic (PK) studies, higher oral bioavailability was observed from DTX-CS-PLGA-NPs (5.11-folds) and DTX-PLGA-NPs (3.29-folds) as compared with DTX-suspension (DTX-S). Cell uptake studies on A549 cells as performed for DTX-CS-PLGA-NPs and DTX-PLGA-NPs loaded with rhodamine 123 dye, exhibited enhanced uptake as compared with plain dye solution. The enhanced uptake for DTX-CS-PLGA-NPs and DTX-PLGA-NPs formulations in the presence of GF120918 was confirmed further with the help of confocal laser scanning microscopic images (CLSM). The potential of the third-generation novel P-gp inhibitor (GF120918) investigated for the effective delivery of DTX as well as investigation of permeability and uptake studies whereby a strong potential of GF120918 for effective oral delivery was established.

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“…6) aer the cells were treated with docetaxel, consistent with immunouorescent microscopy studies of microtubule changes upon the addition of docetaxel to HeLa cells. 36 The results suggest that the amount of microtubules increased in HeLa cells treated with docetaxel. This could explain the reduced factor of viscosity obtained from AFM nanomechanics ( Table 1), in that an increased amount of microtubules could increase the elasticity of the HeLa cells and decrease the viscous deformation, relatively, resulting in a lower factor of viscosity for docetaxel-treated HeLa cells.…”

Section: Cytoskeletal Changesmentioning

confidence: 89%

Interrogation of drug effects on HeLa cells by exploiting new AFM mechanical biomarkers

et al. 2017

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DTX-loaded star-shaped TAPP-PLA-b-TPGS nanoparticles for cancer chemical and photodynamic combination therapy

Abstract: A novel star-shaped copolymer TAPP-PLA-b-TPGS was synthesized as drug nanocarriers for cancer chemical and photodynamic combination therapy.

Cited by 31 publications

References 49 publications

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

Interrogation of drug effects on HeLa cells by exploiting new AFM mechanical biomarkers

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