GLUT1‐Targeting and GSH‐Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy

Wang, Xin; Lu, Yang; Qin, Fang; Xu, Jiaxi; Cheng, Xu; Xue, Yanbing

doi:10.1002/ppsc.202000165

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…The GSH concentration in tumor cells was about 500 times higher than that in normal tissues. The rupture of disulfide bonds of STP-mNPs/DOX led to the continuous release of loaded DOX, thus increasing the necrosis of tumor cells (Wang et al, 2020;Wang et al, 2021). As a result, under the enhanced permeability and retention (EPR) and tumor-targeting effects, STP-mNPs/DOX can accumulate in tumor tissues.…”

Section: Resultsmentioning

confidence: 99%

Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer

Liu

Wang

et al. 2021

Front. Pharmacol.

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Colorectal cancer is the third most common malignant disease worldwide, and chemotherapy has been the standard treatment for colorectal cancer. However, the therapeutic effects of chemotherapy are unsatisfactory for advanced and recurrent colorectal cancers. Thus, increasing the treatment efficacy of chemotherapy in colorectal cancer is a must. In this study, doxorubicin (DOX)-loaded tumor-targeting peptide-decorated mPEG-P(Phe-co-Cys) nanoparticles were developed to treat orthotopic colon cancer in mice. The peptide VATANST (STP) can specifically bind with vimentin highly expressed on the surface of colon cancer cells, thus achieving the tumor-targeting effects. The nanoparticles are core-shell structured, which can protect the loaded DOX while passing through the blood flow and increase the circulation time. The disulfide bonds within the nanoparticles are sensitive to the glutathione-rich microenvironment of tumor tissues. Rupture of disulfide bonds of the nanoparticles leads to the continuous release of DOX, thus resulting in the apoptosis of the tumor cells. The in vivo experiments in mice with orthotopic colon cancer demonstrated that the synthesized DOX-loaded tumor-targeting peptide-decorated polypeptide nanoparticles showed properties of drug delivery systems and exhibited good antitumor properties. The synthesized nanoparticles show appropriate properties as one of the drug delivery systems and exhibit good antitumor properties after encapsulating DOX.

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Section: Resultsmentioning

confidence: 99%

Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer

Liu

Wang

et al. 2021

Front. Pharmacol.

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“…Due to elevated levels of GSH within cells, the pluronic L61 entity of the nanosystem induced intracellular ROS generation, release of cytochrome-c and also disruption of mitochondrial respiration. Intracellular doxorubicin accumulation was observed in cells that led to inhibition of cancer cell growth and tumor development, eventually facilitating the reversal of drug resistance [ 196 ]. Wang and co-workers demonstrated a long-term effect of copper nanoparticles (CuNPs) on CYP450 enzymes in rat brains.…”

Section: Recent Advancements In Nanotechnology To Overcome Mdrmentioning

confidence: 99%

Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer

2022

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Cancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is considered one of the principal reasons for the failure of many forms of clinical chemotherapy. Several factors are involved in the development of MDR including increased expression of efflux transporters, the tumor microenvironment, changes in molecular targets and the activity of cancer stem cells. Recently, researchers have designed and developed a number of small molecule inhibitors and derivatives of natural compounds to overcome various mechanisms of clinical MDR. Unfortunately, most of the chemosensitizing approaches have failed in clinical trials due to non-specific interactions and adverse side effects at pharmacologically effective concentrations. Nanomedicine approaches provide an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and improve therapeutic effectiveness. Multifunctional nanomaterials have been found to facilitate drug delivery by improving bioavailability and pharmacokinetics, enhancing the therapeutic efficacy of chemotherapeutic drugs to overcome MDR. In this review article, we discuss the major factors contributing to MDR and the limitations of existing chemotherapy- and nanocarrier-based drug delivery systems to overcome clinical MDR mechanisms. We critically review recent nanotechnology-based approaches to combat tumor heterogeneity, drug efflux mechanisms, DNA repair and apoptotic machineries to overcome clinical MDR. Recent successful therapies of this nature include liposomal nanoformulations, cRGDY-PEG-Cy5.5-Carbon dots and Cds/ZnS core–shell quantum dots that have been employed for the effective treatment of various cancer sub-types including small cell lung, head and neck and breast cancers. Graphical Abstract

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“…22 Different concentrations of GSH were found in intracellular (2-10 mM) and extracellular (<20 μM) of tumor, 23 with GSH expression in mitochondria high enough (10 mM) to reduce the disulfide bond. 24,25 This was helpful in designing tumor-specific degradation nanoparticles by introducing the redox-responsive groups such as disulfide bond. Meanwhile, the pH value in tumor mitochondria was about 8.0, 26 which is higher than that in normal tissue (pH 7.4) and lysosome (pH 5.5).…”

Section: Introductionmentioning

confidence: 99%

Glutathione Programmed Mitochondria Targeted Delivery of Lonidamine for Effective Against Triple Negative Breast Cancer

Wang¹,

Qin²,

Wang³

et al. 2023

IJN

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Mitochondria are a significant target of lonidamine (LND). However, its limited solubility and inability to specifically target mitochondria, LND can lead to hepatic toxicity and has shown only modest anticancer activity. The objective of this study is to establish a glutathione programmed mitochondria targeted delivery of LND for the effective treatment of triple negative breast cancer (TNBC). Methods: In this study, LND was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) wrapped with mitochondria-targeting short-chain triphenylphosphonium-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and tumor-targeting long-chain 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-S-S-polyethylene glycol-R6RGD (DSPE-S-S-PEG 2000 -R6RGD, DSSR), which were designated as LND-PLGA/TPS/DSSR NPs. The release behavior was evaluated, and cellular uptake, in vitro and in vivo antitumor activity of nanoparticles were investigated. The mechanism, including apoptosis of tumor cells and mitochondrial damage and respiratory rate detection, was also further investigated. Results: LND-PLGA/TPS/DSSR NPs were successfully prepared, and characterization revealed that they are globular particles with smooth surfaces and an average diameter of about 250 nm. Long-chain DSSR in LND-PLGA/TPS/DSSR NPs prevented positively charged LND-PLGA/TPS NPs from being cleared by the reticuloendothelial system. Furthermore, LND release rate from NPs at pH 8.0 was significantly higher than that at pH 7.4 and 5.5, which demonstrated specific LND release in mitochondria and prevented LND leakage in cytoplasm and lysosome. NPs could locate in mitochondria, and the released LND triggered apoptosis of tumor cells by damaging mitochondria and releasing apoptosis-related proteins. In addition, in TNBC mice model, programmed mitochondria targeted NPs improved efficacy and reduced LND toxicity. Conclusion: LND-PLGA/TPS/DSSR NPs may be a useful system and provide an effective approach for the treatment of TNBC.

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GLUT1‐Targeting and GSH‐Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy

Cited by 7 publications

References 33 publications

Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer

Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer

Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer

Glutathione Programmed Mitochondria Targeted Delivery of Lonidamine for Effective Against Triple Negative Breast Cancer

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