Abstract Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work ...nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles.
Cancer stem cells (CSCs) are original cancer cells that are of characteristics associated with normal stem cells. CSCs are toughest against various treatments and thus responsible for cancer ...metastasis and recurrence. Therefore, development of specific and effective treatment of CSCs plays a key role in improving survival and life quality of cancer patients, especially those in the metastatic stage. Nanomedicine strategies, which include prodrugs, micelles, liposomes and nanoparticles of biodegradable polymers, could substantially improve the therapeutic index of conventional therapeutics due to its manner of sustained, controlled and targeted delivery of high transportation efficiency across the cell membrane and low elimination by intracellular autophagy, and thus provide a practical solution to solve the problem encountered in CSCs treatment. This review gives briefly the latest information to summarize the concept, strategies, mechanisms and current status as well as future promises of nanomedicine strategies for treatment of CSCs.
Accumulating evidence has established that long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is a tumor regulator in many cancers. Here, we aimed to investigate the possible ...function of lncRNA PVT1 in esophageal carcinoma (EC) via targeting of microRNA‐145 (miR‐145). Initially, microarray‐based gene expression profiling of EC was employed to identify differentially expressed genes. Moreover, the expression of lncRNA PVT1 was examined and the cell line presenting with the highest level of lncRNA PVT1 expression was selected for subsequent experiments. We then proceeded to examine interaction among lncRNA PVT1, FSCN1, and miR‐145. The effect of lncRNA PVT1 on viability, migration, invasion, apoptosis, and tumorigenesis of transfected cells was examined with gain‐of‐function and loss‐of‐function experiments. We observed that lncRNA PVT1 was robustly induced in EC. lncRNA PVT1 could bind to miR‐145 and regulate its expression, and FSCN1 is a target gene of miR‐145. Overexpression of miR‐145 or silencing of lncRNA PVT1 was revealed to suppress cell viability, migration, and invasion abilities, while also stimulating cell apoptosis. Furthermore, our in vivo results showed that overexpression of miR‐145 or silencing of lncRNA PVT1 resulted in decreased tumor growth in nude mice. In conclusion, our research reveals that down‐regulation of lncRNA PVT1 could potentially promote expression of miR‐145 to repress cell migration and invasion, and promote cell apoptosis through the inhibition of FSCN1. This highlights the potential of lncRNA PVT1 as a therapeutic target for EC treatment.
lncRNA PVT1 can specifically compete with miR‐145 to inhibit its expression, thereby increasing FSCN1 expression. This in turn promotes proliferation, invasion, and migration of EC cells by up‐regulating the expression of MAT1, CD147, and VEGFR2. Moreover, down‐regulation of lncRNA PVT1 can up‐regulate expression of miR‐145 to inhibit the expression of FSCN1.
A general strategy for the preparation of highly fluorescent poly(DL‐lactide‐co‐glycolide) (PLGA) nanoparticles (NPs) loaded with conjugated polymers (CPs) is reported. The process involves ...encapsulation of organic‐soluble CPs with PLGA using a modified solvent extraction/evaporation technique. The obtained NPs are stable in aqueous media with biocompatible and functionalizable surfaces. In addition, fluorescent properties of the CP‐loaded PLGA NPs (CPL NPs) could be fine‐tuned by loading different types of CPs into the PLGA matrix. Four types of CPL NPs are prepared with a volume‐average hydrodynamic diameter ranging from 243 to 272 nm. The application of CPL NPs for bio‐imaging is demonstrated through incubation with MCF‐7 breast cancer cells. Confocal laser scanning microscopy studies reveal that the CPL NPs are internalized in cytoplasm around the nuclei with intense fluorescence. After conjugation with folic acid, cellular uptake of the surface‐functionalized CPL NPs is greatly enhanced via receptor‐mediated endocytosis by MCF‐7 breast cancer cells, as compared to that for NIH/3T3 fibroblast cells, which indicates a selective targeting effect of the folate‐functionalized CPL NPs in cellular imaging. The merits of CPL NPs, such as low cytotoxicity, high fluorescence, good photostability, and feasible surface functionalization, will inspire extensive study of CPL NPs as a new generation of probes for specific biological imaging and detection.
A generic strategy for the fabrication of highly fluorescent conjugated‐polymer‐loaded poly(DL‐lactide‐co‐glycolide) nanoparticles is developed. This method may serve to produce a new generation of biocompatible, surface‐functionalizable probes for targeted cancer cell imaging and diagnostics.
Double emulsion has been used most often in formulation of hydrophilic drugs by nanoparticles of biodegradable polymers, which has disadvantages such as low drug loading and low drug encapsulation ...efficiency due to the drug loss in the process. The drug release may be too fast for sustained chemotherapy. We developed in this research a d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) prodrug micelle system with cisplatin as a model hydrophilic drug. We demonstrated that such a system can successfully deliver the model hydrophilic drug with a low critical micelle concentration (CMC) of only 5.01mg/L, a high drug load of 4.95% (w/w) and a pH-responsive drug release kinetics and higher cellular uptake in comparison with the original drug and the TPGS-cisplatin prodrug itself. The cell viability experiment showed great enhancement of the cisplatin chemotherapy, which is demonstrated by the IC50 value reduced from 3.95, 0.98, 0.19 for cisplatin to 1.36, 0.51, 0.08μg/mL for the TPGS prodrug micelle formulation after 24, 48, 72h culture with the HepG2 hepatocarcinoma cells, respectively. Furthermore, such a TPGS prodrug micellar formulation showed significant neuroprotective effects for the cisplatin chemotherapy, which is demonstrated by the greatly increased IC50 value for the SH-SY5Y neuroblast-like cells in comparison between cisplatin and the TPGS prodrug micelle formulation. The TPGS prodrug micelles can also be generalized to become a new strategy for codelivery of hydrophilic and hydrophobic drugs and/or imaging agents.
Abstract We developed a system of Cetuximab-conjugated micelles of vitamin E TPGS for targeted delivery of docetaxel as a model anticancer drug for treatment of the triple negative breast cancer ...(TNBC), which shows no expression of either one of the hormone progesterone receptor (PR), estrogen receptor (ER) and epidermal growth factor receptor 2 (HER2) and is thus more difficult to be treated than the positive breast cancer. Such micelles are of desired particle size, drug loading, drug encapsulation efficiency and drug release profile. Their surface morphology, surface charge and surface chemistry were also characterized. The fibroblast cells (NIH3T3), HER2 overexpressed breast cancer cells (SK-BR-3), ER and PR overexpressed breast cancer cells (MCF7), and TNBC cells of high, moderate and low EGFR expression (MDA MB 468, MDA MB 231 and HCC38) were employed to access in vitro cellular uptake of the coumarin 6 loaded TPGS micelles and cytotoxicity of docetaxel formulated in the micelles. The high IC50 value, which is the drug concentration needed to kill 50% of the cells in a designated period such as 24 h, obtained from Taxotere® showed that the TNBC cells are indeed more resistant to the free drug than the positive breast cancer cells. However, the therapeutic effects of docetaxel could be greatly enhanced by the formulation of Cetuximab conjugated TPGS micelles, which demonstrated 205.6 and 223.8 fold higher efficiency than Taxotere® for the MDA MB 468 and MDA MB 231 cell lines respectively.
This work developed a system of nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of anticancer drugs with paclitaxel as a model drug, in which the emphasis ...was given to the effects of the surfactant type and the optimization of the emulsifier amount used in the single emulsion solvent evaporation/extraction process for the nanoparticle preparation on the particle size, characters and
in vitro performance. The drug loaded nanoparticles were characterized by laser light scattering (LLS) for size and size distribution, field-emission scanning electron microscopy (FESEM) for surface morphology, X-ray photoelectron spectroscopy (XPS) for surface chemistry, zetasizer for surface charge, and high performance liquid chromatography (HPLC) for drug encapsulation efficiency and
in vitro drug release kinetics. MCF-7 breast cancer cells were employed to evaluate the cellular uptake and cytotoxicity. It was found that phospholipids of short chains such as 1,2-dilauroylphosphatidylocholine (DLPC) have great advantages over the traditional emulsifier poly(vinyl alcohol) (PVA), which is used most often in the literature, in preparation of nanoparticles of biodegradable polymers such as poly(
d,
l-lactide-co-glycolide) (PLGA) for desired particle size, character and
in vitro cellular uptake and cytotoxicity. After incubation with MCF-7 cells at 0.250
mg/ml NP concentration, the coumarin-6 loaded PLGA NPs of DLPC shell showed more effective cellular uptake versus those of PVA shell. The analysis of IC
50, i.e. the drug concentration at which 50% of the cells are killed, demonstrated that our DLPC shell PLGA core NP formulation of paclitaxel could be 5.88-, 5.72-, 7.27-fold effective than the commercial formulation Taxol
® after 24, 48, 72
h treatment, respectively.
Abstract We synthesized nanoparticles (NPs) of the blend of two-component copolymers for targeted chemotherapy with paclitaxel used as model drug. One component is poly(lactide)– d -α-tocopheryl ...polyethylene glycol succinate (PLA–TPGS), which is of desired hydrophobic–lipophilic balance, and another is TPGS–COOH, which facilitates the folate conjugation for targeting. The nanoparticles of the two-copolymer blend at various component ratio were prepared by the solvent extraction/evaporation single emulsion method and then decorated by folate, which were characterized by laser light scattering (LLS) for particles' size and size distribution, zeta potential analyzer for surface charge, and X-ray photoelectron spectroscopy (XPS) for surface chemistry. The drug encapsulation efficiency (EE) and in vitro drug release were measured by high performance liquid chromatography (HPLC). The targeting effect was investigated in vitro by cancer cell uptake of coumarin-6-loaded NPs and further confirmed by cytotoxicity of cancer cells treated with the drug formulated in the NPs. We showed that the NP formulation has great advantages vs the pristine drug in achieving better therapeutic effect, which increased 8.68% for MCF-7 breast cancer cells, and that the folate-decoration can significantly promote targeted delivery of the drug into the corresponding cancer cells and thus enhance its therapeutic effect, which increased 24.4% for the NP formulation of 16.7% TPGS–COOH component and 31.1% for the NP formulation of 33.3% TPGS–COOH component after 24 h treatment at the same 25 μg/ml paclitaxel concentration. The experiments on C6 glioma cells further confirmed these advantages.
Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized and used to make nanoparticles by the nanoprecipitation method for clinical administration of antineoplastic drugs. ...Paclitaxel was used as a prototype drug due to its excellent efficacy and commercially great success. The size and size distribution, surface morphology, surface charge and surface chemistry of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, atomic force microscopy, zeta-potential analyzer and X-ray photoelectron spectroscopy (XPS). The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography. The effects of various formulation parameters were evaluated. The prepared nanoparticles were found of spherical shape with size less than 100
nm. Zeta potential measurement and XPS analysis demonstrated the presence of PEG layer on the particle surface. Viscosity of the organic phase was found to be one of the main process factors for the size determination. The EE was found to be greatly influenced by the drug loading. The drug release pattern was biphasic with a fast release rate followed by a slow one. The particle suspension exhibited good steric stability in vitro. Such a nanoparticle formulation of paclitaxel can be expected to have long-circulating effects in circulation.
Purpose
To design a quick checklist for urodynamic study (UDS), aiming to reduce the occurrence of errors in the process, which may help to increase the quality of UDS. And further to analyze the ...effectiveness of this quick checklist for UDS quality control.
Methods
First, a quick checklist for uroflow study and pressure‐flow study was developed, based on the International Continence Society‐Good Urodynamic Practice standards, our previous studies, and recent literature, as well as expert suggestions. Then, patients who underwent UDS between January 2023 to February 2023 were randomly assigned to a study group or a control group. For the study group, the quick checklist was used throughout the UDS process, while the control group did not. The main artefacts were chosen to verify the effectiveness of the quick checklist for improving the UDS quality.
Results
The quick checklist comprised three subtypes: checklist for patients, checklist for environment and device, and checklist for UDS test process. 38 UDS traces per group were included. The incidence of missing the standard cough test decreased significantly from 18.4% to 0 (p = 0.012), with the checklist implementation. The baseline drift frequency rate also declined significantly from 39.5% to 5.3% (p < 0.05). Volume < 150 mL on uroflow study occurred in 68.4% of cases and its frequency rate decreased significantly with checklist implementation (p < 0.05).
Conclusion
A quick checklist for quality control of UDS was developed. The quick checklist as a convenient, quick, and easy used urodynamic quality control method, may help to reduce the technical artefacts and improve fundamental urodynamic quality control. Future research with a larger sample size is needed to confirm the effectiveness of the checklist.
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