ROS-triggered and regenerating anticancer nanosystem: An effective strategy to subdue tumor's multidrug resistance

Su, Zhigui; Chen, Minglei; Xiao, Yanyu; Sun, Minjie; Zong, Li; Asghar, Sajid; Dong, Mei; Li, Huipeng; Ping, Qineng; Zhang, Can

doi:10.1016/j.jconrel.2014.09.020

Cited by 95 publications

(82 citation statements)

References 40 publications

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“…Fluorescent intensity of DOX-PENPs in MCF-7 cells at 20 μg/mL concentration and at 4 h was significantly enhanced as HA-based CD44 targeting could have promoted the endocytosis of nanoparticles by cells. 44 MCF-7/ADR cells' uptake of DOX solution was much lower than the MCF-7 cells, indicating obvious efflux of DOX from MCF-7/ADR cells. PENPs co-loaded with VRP could improve MCF-7/ ADR cell uptake of DOX significantly, which suggests that the VRP could inhibit the extracellular efflux mechanism of DOX-VRP-PENPs in MCF-7/ADR cells by P-gp.…”

Section: Cellular Uptake Studymentioning

confidence: 87%

Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to overcome multidrug resistance in breast tumor

Xu¹,

Asghar²,

Gao³

et al. 2017

IJN

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The aim of this study was to evaluate the potential of polyelectrolyte complex nanoparticles (PENPs) based on hyaluronic acid/chitosan hydrochloride (HA/HCS) for co-loading mitoxantrone (MTO) and verapamil (VRP) to overcome multidrug resistance in breast tumors. PENPs co-loaded with MTO and VRP (MTO-VRP-PENPs) were affected by the method of preparation, molecular weight of HA, mass ratios and initial concentrations of HA/HCS, pH, and drug quantities. Optimized MTO-VRP-PENPs were ~209 nm in size with a zeta potential of approximately −24 mV. Encapsulation efficiencies (%) of MTO and VRP were 98.33%±0.27% and 44.21%±8.62%, respectively. MTO and VRP were successfully encapsulated in PENPs in a molecular or amorphous state. MTO-VRP-PENPs showed significant cytotoxicity in MCF-7/ADR cells in contrast to MTO-loaded PENPs (MTO-PENPs). The reversal index of MTO-VRP-PENPs was 13.25 and 10.33 times greater than that of the free MTO and MTO-PENPs, respectively. In conclusion, MTO-VRP-PENPs may serve as a promising carrier to overcome tumor drug resistance.

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Section: Cellular Uptake Studymentioning

confidence: 87%

Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to overcome multidrug resistance in breast tumor

Xu¹,

Asghar²,

Gao³

et al. 2017

IJN

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“…This might be related to the difference of the intracellular ROS basal values between two cells, which was affected by the generation and consumption of ROS. 39 The ROS basal value of MCF-7/PTX cells was higher than that of MCF-7 cells (Figure 2A), which meant that the consumption of ROS caused by reducing agent showed little effects on MCF-7/PTX cells. FSST and Notes: *P,0.05, **P,0.01: significantly different from F127 group.…”

Section: Effects Of Polymers On Intracellular Ros Levelmentioning

confidence: 91%

Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Lin¹,

Zhao²,

Liu³

et al. 2018

IJN

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Introduction The development of nanodrug carriers utilizing tumor microenvironment has become a hotspot in reversing multidrug resistance (MDR). Materials and methods This study synthesized a redox-sensitive copolymer, Pluronic F127-disulfide bond- d -α-tocopheryl polyethylene glycol 1000 succinate (FSST), through the connection of the reduction-sensitive disulfide bond between F127 and d -α-tocopheryl polyethylene glycol 1000 succinate. This polymer could induce the elevation of reactive oxygen species (ROS) levels, ultimately resulting in cytotoxicity. Moreover, the redox-responsive mixed micelles, F127-folate (FA)/FSST/P123 (FFSSTP), based on FSST, Pluronic F127-FA, and Pluronic P123, were prepared to load paclitaxel (PTX). Results The in vitro release study demonstrated that FFSSTP/PTX accelerated the PTX release through the breakage of disulfide bond in reductive environment. In cellular experiment, FFSSTP/PTX induced significant apoptosis in PTX-resistant MCF-7/PTX cells through inhibiting adenosine triphosphate (ATP)-binding cassette proteins from pumping out PTX by interfering with the mitochondrial function and ATP synthesis. Furthermore, FFSSTP/PTX induced apoptosis through elevating the intracellular levels of ROS. Conclusion FFSSTP could become a potential carrier for the treatment of MDR tumors.

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“…37 When DiO/ DiI-coloaded micelles were excited at 484 nm, the emission energy of DiO would be transferred to DiI, resulting in quenching of DiO's signal and appearance of a strong DiI signal. 19 The result indicated that after being incubated with 100 µg/mL MMP-2/9 for 2 hours, the ratio of IR/(IG+IR) in TGK micelles decreased significantly (P,0.01), which was not observed with the T2K micelles (Figure 4). Once the peptide was cleaved, DiI and DiO would be released from the hydrophobic core of TGK micelles, resulting in the disappearance of FRET.…”

mentioning

confidence: 87%

“…17 d-α-Tocopherol succinate (α-TOS) and its analogs can induce reactive oxygen species generation, subsequently inducing apoptosis in cancer cells while being nontoxic toward normal cells. 18,19 TPGS has also been approved by the US Food and Drug Administarion as a safe pharmaceutical adjuvant used in drug formulation. 20 Besides, it was reported that TPGS could be efficient in overcoming multidrug resistance.…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation

Zhang

Wang

Zhong

et al. 2016

IJN

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Since elevated expression of matrix metalloproteinase (MMP)-2 and MMP-9 is commonly observed in several malignant tumors, MMPs have been widely reported as key factors in the design of drug delivery systems. Several strategies have been proposed to develop MMPs-responsive nanoparticles to deliver chemotherapeutics to malignant solid tumors. A stimuli-responsive drug delivery system, which could be cleaved by MMPs, was proposed in this study. By inserting an MMP-2/9 cleavable oligopeptide GPVGLIGK-NH 2 (GK8) as spacer between α-tocopherol succinate (α-TOS) and methoxy-polyethylene glycol molecular weight (MW 2000 Da) activated by N -hydroxysuccinimide (mPEG2K-NHS), mPEG2K-GK8-α-TOS (TGK) was synthesized as the primary ingredient for MMP-2/9-sensitive micelles composed of d -α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and TGK (n:n =40:60, TGK micelles). mPEG2K-α-TOS (T2K) was similarly synthesized as nonsensitive control. The TGK micelles showed better stability than nonsensitive micelles composed of TPGS and T2K (n:n =40:60, T2K micelles) owing to the inserted peptide. Fluorescence resonance energy transfer results indicated that TGK micelles could be successfully cleaved by MMP-2/9. Effective drug release was demonstrated in the presence of collagenase type IV, a mixture of MMP-2 and MMP-9. Compared with nonsensitive micelles, docetaxel (DTX)-loaded TGK micelles showed a fold higher cellular uptake in HT1080 cells. While the half-maximal inhibitory concentration (IC 50 ) of TGK and T2K micelles were similar ( P >0.05) in MCF-7 cells (MMP-2/9 underexpression), the IC 50 values of the aforementioned micelles were 0.064±0.006 and 0.122±0.009 μg/mL, respectively, in HT1080 cells (MMP-2/9 overexpression). The MMP-2/9-sensitive micelles also demonstrated desired tumor targeting and accumulation ability in vivo. The results of in vivo antitumor effect evaluation indicate that TGK micelles are potent against solid tumors while maintaining minimum systemic toxicity compared with T2K micelles and DTX.

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ROS-triggered and regenerating anticancer nanosystem: An effective strategy to subdue tumor's multidrug resistance

Cited by 95 publications

References 40 publications

Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to overcome multidrug resistance in breast tumor

Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to overcome multidrug resistance in breast tumor

Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation

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ROS-triggered and regenerating anticancer nanosystem: An effective strategy to subdue tumor's multidrug resistance

Cited by 95 publications

References 40 publications

Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to overcome multidrug resistance in breast tumor

Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to overcome multidrug resistance in breast tumor

Redox-responsive F127-folate/F127-disulfide bond-D-&alpha;-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation

Contact Info

Product

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Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors