Self-assembly PEGylation assists SLN-paclitaxel delivery inducing cancer cell apoptosis upon internalization

Arranja, Alexandra; Gouveia, Luís F.; Gener, Petra; Rafael, Diana; Pereira, Carolina; Videira, Mafalda

doi:10.1016/j.ijpharm.2016.01.075

Cited by 24 publications

(7 citation statements)

References 37 publications

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“…Paclitaxel's mode of antitumor action is the disruption of microtubule dynamics, and paclitaxel is believed to mediate G2/M cell cycle arrest in various cancer cells, including GC (30)(31)(32). In our study, after different treatments, G2/M arrest was frequently observed in NCI-N87 cells.…”

Section: Discussionmentioning

confidence: 53%

Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptorï¿½2-positive gastric cancer

et al. 2018

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Gastric cancer (GC) is the most lethal malignancy in the digestive system. This study investigated an antibodynanoparticle conjugate (ANC) constructed with trastuzumab (Herceptin ®) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane ®) (trastuzumab/nab-paclitaxel) as a novel strategy of targeted therapy for human epidermal growth factor receptor 2 (HER2) positive GC. The ANC was fabricated with trastuzumab and nab-paclitaxel by a 'one-step' synthesis using EDC/NHS. In vitro antitumor efficacy was evaluated by cell viability, apoptosis rate and cell cycle of HER2-positive GC NCI-N87 cells and compared with paclitaxel (Taxol ®), nab-paclitaxel and trastuzumab/nab-paclitaxel. In addition, GC xenograft models were established to evaluate antitumor efficacy in vivo. These results demonstrated that trastuzumab/nab-paclitaxel was spherical with a suitable size (139.18±32.06 nm). The half-maximal inhibitory concentration (IC 50) for NCI-N87 cells was 0.24±0.08, 0.13±0.03 and 0.048±0.01 µg/ml of paclitaxel, nab-paclitaxel and trastuzumab/nab-paclitaxel, respectively. Compared with paclitaxel and nab-paclitaxel, trastuzumab/nab-paclitaxel could induce a higher rate of apoptosis and significant G2/M arrest. At 4 weeks after treatment, tumor-bearing mice had a mean tumor volume of 233±24 mm 3 treated by trastuzumab/nab-paclitaxel, 559±97 mm 3 by nab-paclitaxel, 871±94 mm 3 by paclitaxel and 1,576±190 mm 3 by PBS as control, respectively, which showed that trastuzumab/nab-paclitaxel could surpass nab-paclitaxel and paclitaxel in antitumor effect. Furthermore, the NIR imaging indicated that trastuzumab/nab-paclitaxel labeled by NIR-797 could more precisely focus on tumor regions. In conclusion, trastuzumab/nab-paclitaxel could mediate targeted therapy and enhance antitumor efficacy, which could represent a novel therapeutic agent for HER2-positive GC.

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Section: Discussionmentioning

confidence: 53%

Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptorï¿½2-positive gastric cancer

et al. 2018

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“…Moreover, PEG chains are cleaved by matrix metalloproteinases, which allows for their efficient application in tumor cells where the concentration of these proteinases is increased in surrounding areas [ 114 ]. Several studies have even taken advantage on the functionalization with PEG chains and have combined it with other targeting molecules such as carboxylic acids or amines present in different targeting ligands [ 81 , 101 , 108 , 115 , 116 ].…”

Section: Preparation Methods and Functionalization Approachesmentioning

confidence: 99%

Solid Lipid Nanoparticles as Carriers of Natural Phenolic Compounds

et al. 2020

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Phenolic compounds are one of the most widespread classes of compounds in nature, with several beneficial biological effects being associated with their anti-oxidant and anti-carcinogenic activities. Their application in the prevention or treatment of numerous chronic diseases have been studied, but a major drawback is still the low bioavailability of these compounds, as well as their instability towards pH, temperature, and light in some cases. Nanotechnology has emerged as an alternative to overcome these limitations, and the use of lipidic encapsulation systems is a promising technique to achieve an efficient drug delivery, protecting molecules from external factors and improving their bioavailability. In this review, solid lipid nanoparticles and nanostructured lipid carriers are highlighted as an important tool for the improvement of the bioavailability and stability of natural phenolic compounds, including their preparation methods and functionalization approaches and the discussion of several applications for putative use in cosmetic and pharmacologic products.

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“…In both cell lines, PEGylated PN displayed slightly lower cytotoxicity than PN. It was speculated that the PEG-modified nanoparticles may affect affinity and internalization, leading to weaker anti-proliferation activity (Arranja et al, 2016;Rao et al, 2017). In cancerous 4T1 cell line ( Figure 5(A)), the PNM exhibited the strongest antitumor effect among all the formulations with reduced IC 50 values than PN ( Supplementary Table S3).…”

Section: Cellular Uptake and Cytotoxicity Studiesmentioning

confidence: 99%

“…Interestingly, liver signals in the PDNM group decreased more rapidly compared to that in PDN group. It was probably because of entrapment of PDN in livers while the PDNM successfully escaped from RES (Arranja et al, 2016; Figure 6(A)). These data illustrated that EM-based long circulation effect together with EPR effect by nanoparticles could achieve preferential drug accumulations in tumor tissue.…”

Section: In Vivo Imaging Of the Fluorescence-labeled Pnmmentioning

confidence: 99%

Erythrocyte-mimicking paclitaxel nanoparticles for improving biodistributions of hydrophobic drugs to enhance antitumor efficacy

Zhai

Yao

et al. 2020

Drug Delivery

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Recent decades have witnessed several nanocrystal-based hydrophobic drug formulations because of their excellent performance in improving drug loading and controlling drug release as mediate drug forms in tablets or capsules. However, the intravenous administration of drug nanocrystals was usually hampered by their hydrophobic surface properties, causing short half-life time in circulation and low drug distribution in tumor. Here, we proposed to enclose nanocrystals (NC) of hydrophobic drug, such as paclitaxel (PTX) into erythrocyte membrane (EM). By a series of formulation optimizations, spherical PTX nanoparticles (PN) with the particle size of around 280 nm were successfully cloaked in erythrocyte membrane, resulting in a PTX-NP-EM (PNM) system. The PNM could achieve high drug loading of PTX (>60%) and stabilize the particle size significantly compared to PN alone. Besides, the fluorescence-labeling PNM presented better tumor cell uptake, stronger cytotoxicity, and higher drug accumulation in tumor compared to PN. Finally, the PNM was found to be the most effective against tumor growth among all PTX formulations in tumor-bearing mice models, with much lower system toxicity than control formulation. In general, the PNM system with high drug-loading as well as superior bio-distributions in vivo could be served as a promising formulation.

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Self-assembly PEGylation assists SLN-paclitaxel delivery inducing cancer cell apoptosis upon internalization

Cited by 24 publications

References 37 publications

Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptorï¿½2-positive gastric cancer

Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptorï¿½2-positive gastric cancer

Solid Lipid Nanoparticles as Carriers of Natural Phenolic Compounds

Erythrocyte-mimicking paclitaxel nanoparticles for improving biodistributions of hydrophobic drugs to enhance antitumor efficacy

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