Dataset Information

Ditelluride-Bridged PEG-PCL Copolymer as Folic Acid-Targeted and Redox-Responsive Nanoparticles for Enhanced Cancer Therapy.

ABSTRACT: The development of the nanosized delivery systems with targeting navigation and efficient cargo release for cancer therapy has attracted great attention in recent years. Herein, a folic acid (FA) modified PEGylated polycaprolactone containing ditelluride linkage was synthesized through a facile coupling reaction. The hydrophobic doxorubicin (DOX) can be encapsulated into the polymeric micelles, and such nanoparticles (F-TeNPDOX) exhibited redox-responsive drug release under abundant glutathione (GSH) condition due to the degradation of ditelluride bonds. In addition, flow cytometric analyses showed that the FA ligands on F-TeNPDOX could facilitate their cellular uptake in 4T1 breast cancer cells. Therefore, F-TeNPDOX led to the promoted drug accumulation and enhanced growth inhibition on 4T1 tumor in vivo. The obtained results suggest F-TeNPDOX excellent potential as nanocarriers for anticancer drug delivery.

SUBMITTER: Pang Z

PROVIDER: S-EPMC7059598 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Ditelluride-Bridged PEG-PCL Copolymer as Folic Acid-Targeted and Redox-Responsive Nanoparticles for Enhanced Cancer Therapy.

Pang Zekun Z Zhou Jiayan J Sun Chunyang C

Frontiers in chemistry 20200228

The development of the nanosized delivery systems with targeting navigation and efficient cargo release for cancer therapy has attracted great attention in recent years. Herein, a folic acid (FA) modified PEGylated polycaprolactone containing ditelluride linkage was synthesized through a facile coupling reaction. The hydrophobic doxorubicin (DOX) can be encapsulated into the polymeric micelles, and such nanoparticles (F-TeNP<sub>DOX</sub>) exhibited redox-responsive drug release under abundant g ...[more]

PMID: 32181244

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Project description:An amphiphilic copolymer, folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) was prepared and explored as a nanometer carrier for the co-delivery of cisplatin (cis-diaminodichloroplatinum, CDDP) and paclitaxel (PTX). CDDP and PTX were encapsulated inside the hydrophobic inner core and chelated to the middle shell, respectively. PEG provided the outer corona for prolonged circulation. An in vitro release profile of the CDDP + PTX-encapsulated nanoparticles revealed that the PTX chelation cross-link prevented an initial burst release of CDDP. After an incubation period of 24 hours, the CDDP+PTX-encapsulated nanoparticles exhibited a highly synergistic effect for the inhibition of A549 (FA receptor negative) and M109 (FA receptor positive) lung cancer cell line proliferation. Pharmacokinetic experiment and distribution research shows that nanoparticles have longer circulation time in the blood and can prolong the treatment times of chemotherapeutic drugs. For the in vivo treatment of A549 cells xeno-graft lung tumor, the CDDP+PTX-encapsulated nanoparticles displayed an obvious tumor inhibiting effect with an 89.96% tumor suppression rate (TSR). This TSR was significantly higher than that of free chemotherapy drug combination or nanoparticles with a single drug. For M109 cells xeno-graft tumor, the TSR was 95.03%. In vitro and in vivo experiments have all shown that the CDDP+PTX-encapsulated nanoparticles have better targeting and antitumor effects in M109 cells than CDDP+PTX-loaded PEG-PLGA nanoparticles (p < 0.05). In addition, more importantly, the enhanced anti-tumor efficacy of the CDDP+PTX-encapsulated nanoparticles came with reduced side-effects. No obvious body weight loss or functional changes occurred within blood components, liver, or kidneys during the treatment of A549 and M109 tumor-bearing mice with the CDDP+PTX-encapsulated nanoparticles. Thus, the FA modified amphiphilic copolymer-based combination of CDDP and PTX may provide useful guidance for effective and safe cancer chemotherapy, especially in tumors with high FA receptor expression.

Project description:In this work, we aimed to improve the encapsulation efficiency of sepiapterin (SP), the natural precursor of the essential cofactor tetrahydrobiopterin (BH4) that displays mild water-solubility and a short biological half-life, within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone)(mPEG-PCL) nanoparticles (NPs) by means of its complexation and hydrophobization with 2,3,6-triacetyl-β-cyclodextrin (TAβCD). For this, SP/TAβCD complexes were produced by spray-drying of SP/TAβCD binary solutions in ethanol using the Nano Spray Dryer B-90 HP. Dry powders were characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and transmission and scanning electron microscopy (TEM and SEM, respectively) and compared to the pristine components and their physical mixtures (PMs). Next, SP was encapsulated within mPEG-PCL NPs by nano-precipitation of an SP/TAβCD complex/mPEG-PCL solution. In addition to the nano-encapsulation of a preformed complex within the polymeric NPs, we assessed an alternative encapsulation approach called drying with copolymer (DWC) in which pristine SP, TAβCD, and mPEG-PCL were co-dissolved in a mixture of acetone and methanol at the desired weight ratio, dried under vacuum, re-dissolved, and nano-precipitated in water. The dissolution-drying step was aimed to promote the formation of molecular hydrophobic interactions between SP, TAβCD, and the PCL blocks in the copolymer. SP-loaded mPEG-PCL NPs were characterized by dynamic light scattering (DLS) and SEM. NPs with a size of 74-75 nm and standard deviation (S.D., a measure of the peak width) of 21-22 nm were obtained when an SP:TAβCD (1:1 molar ratio) spray-dried complex was used for the nano-encapsulation and SEM analysis revealed the absence of free SP crystals. The encapsulation efficiency (%EE) and drug loading (%DL) were 85% and 2.6%, respectively, as opposed to the much lower values (14% and 0.6%, respectively) achieved with pristine SP. Moreover, the NPs sustained the SP release with relatively low burst effect of 20%. Overall, our results confirmed that spray-drying of SP/TAβCD solutions at the appropriate molar ratio leads to the hydrophobization of the relatively hydrophilic SP molecule, enabling its encapsulation within mPEG-PCL NPs and paves the way for the use of this strategy in the development of novel drug delivery systems of this vital biological precursor.

Dataset Information

Ditelluride-Bridged PEG-PCL Copolymer as Folic Acid-Targeted and Redox-Responsive Nanoparticles for Enhanced Cancer Therapy.

Publications

Ditelluride-Bridged PEG-PCL Copolymer as Folic Acid-Targeted and Redox-Responsive Nanoparticles for Enhanced Cancer Therapy.

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