Redox/pH dual-sensitive hybrid micelles for targeting delivery and overcoming multidrug resistance of cancer

Yin, Mingxing; Bao, Yuling; Gao, Xueqin; Wu, Yupei; Sun, Yu; Zhao, Xinyuan; Xu, Hang; Zhang, Zhiping; Tan, Songwei

doi:10.1039/c6tb03282f

Cited by 39 publications

(29 citation statements)

References 37 publications

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“…As shown in Figure 11C, when the concentration of Rh123 was 5, 10 and 20 μg/mL, the mean fluorescence intensity of the MCF-7 cells was 108.5-, 147.8-and 155.9-folds higher than that of MCF-7/ADR cells, respectively, which indicated that MCF-7/ADR cells retained strong MDR properties, while the MCF-7 cells were relatively sensitive. 35 Furthermore, the drug efflux inhibition was evaluated on different NPs using MCF-7/ADR cells. As shown in Figure 11D, the mean fluorescence intensity of Rh123 in the cells treated with taxol did not alter significantly.…”

Section: Inhibition Of P-gp Analysismentioning

confidence: 99%

“…12,35 The transport activity of P-gp was first studied in MCF-7/ADR and MCF-7 cells via fluorescence spectrophotometer. Briefly, MCF-7/ADR or MCF-7 cells were seeded in 24-well plates at 5×10 4 cells/ well.…”

Section: Rhodamine 123 (Rh123) Efflux Assaymentioning

confidence: 99%

“…MCF-7/ADR was obtained from Central South University (Changsha, People's Republic of China) and maintained in media containing DOX at a concentration of 1 μg/mL as reported previously. 12,35 All cell experiments were performed according to protocols evaluated and approved by the ethics committee of Nanjing Medical University.…”

mentioning

confidence: 99%

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pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Huo¹,

Zhu²,

Niu³

et al. 2017

IJN

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Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glyco-protein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)- block -poly( l -lysine) (PEG- b -PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l -lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy.

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Section: Inhibition Of P-gp Analysismentioning

confidence: 99%

Section: Rhodamine 123 (Rh123) Efflux Assaymentioning

confidence: 99%

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pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Huo¹,

Zhu²,

Niu³

et al. 2017

IJN

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“…In brief, a series of drug-free LC-SA/CS-SA micelle solution with various micelle concentrations from 0.001 to 0.5 mg/ml were prepared, and 1 ml of pyrene-in-acetone solution (6 Â 10 À5 M) was added into the micelle solutions respectively and sonicated for dissolution to obtain the final pyrene concentration of 6 Â 10 À7 M. The pre-prepared solutions were equilibrated overnight at 28 C, and the emission spectra of the solutions from 350 nm to 500 nm were recorded at an excitation wavelength of 337 nm by fluorescence spectrophotometer (RF-5301PC, Shimadzu Corporation, Kyoto, Japan). The CMC value was defined as the crosspoint of the two regression lines based on the intensity ratios of first peak at 373 nm to third peak at 384 nm vs. the concentrations of micelle material (Dong et al, 2017;Yang et al, 2017;Yin et al, 2017).…”

Section: Critical Micelle Concentration (Cmc)mentioning

confidence: 99%

l -Carnitine conjugated chitosan-stearic acid polymeric micelles for improving the oral bioavailability of paclitaxel

et al. 2020

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A delivery system based on L-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 lg/ml. The drug-loaded micelles presented a slow and incomplete in vitro release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.

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“…However, the therapeutic efficacy of chemotherapy is usually limited by multidrug resistance (MDR), especially in advanced stages of cancer. 3,4 Although the mechanism of MDR is complex, the overexpression of P-glycoprotein (P-gp) encoded by the MDR1 gene in cancer cells has been regarded as the major mechanism of MDR, which is able to pump various chemotherapeutics, such as doxorubicin (DOX) and paclitaxel (PTX), out of the cells, leading to low intracellular concentration of drug to kill the cells.…”

Section: Introductionmentioning

confidence: 99%

A simple reduction-sensitive micelles co-delivery of paclitaxel and dasatinib to overcome tumor multidrug resistance

Li¹,

Lü

et al. 2017

IJN

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Multidrug resistance (MDR) is one of the major obstacles in successful chemotherapy. The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating MDR tumor is a good strategy to overcome MDR. In this work, we prepared the simple redox-responsive micelles based on mPEG-SS-C 18 as a co-delivery system to load the paclitaxel (PTX) and dasatinib (DAS) for treatment of MCF-7/ADR cells. The co-loaded micelles had a good dispersity and a spherical shape with a uniform size distribution, and they could quickly disassemble and rapidly release drugs under the reduction environment. Compared with MCF-7 cells, the DAS and PTX co-loaded redox-sensitive micelle (SS-PDNPs) showed stronger cytotoxicity and a more improving intracellular drug concentration than other drug formulations in MCF-7/ADR cells. In summary, the results suggested that the simple co-delivery micelles of PTX and DAS possessed significant potential to overcome drug resistance in cancer therapy.

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Redox/pH dual-sensitive hybrid micelles for targeting delivery and overcoming multidrug resistance of cancer

Abstract: A three-step approach was used to enhance anticancer activity via targeted delivery, intracellular drug burst release, and depressed drug efflux.

Cited by 39 publications

References 37 publications

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

l -Carnitine conjugated chitosan-stearic acid polymeric micelles for improving the oral bioavailability of paclitaxel

A simple reduction-sensitive micelles co-delivery of paclitaxel and dasatinib to overcome tumor multidrug resistance

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