Doxorubicin and adjudin co-loaded pH-sensitive nanoparticles for the treatment of drug-resistant cancer

Wang, Qiong; Zou, Chenming; Wang, Lingying; Gao, Xueqin; Wu, Jindan; Tan, Songwei; Wu, Gang

doi:10.1016/j.actbio.2019.05.061

Cited by 47 publications

(30 citation statements)

References 49 publications

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“…Previous research highlighted that ADD is a mitochondrial inhibitor that can diminish ATP supply and mediate apoptosis by disrupting mitochondrial function; consequently reducing the excretion of intracellular chemotherapeutics such as doxorubicin (Li et al., 2015 ; Qi et al., 2018 ; Wang et al., 2019 ). Here, we studied the effect of ADD on mitochondrial function and used the JC-1 method to determine the mitochondrial membrane potential.…”

Section: Resultsmentioning

confidence: 99%

“…Adjudin (ADD), an analogue of lonidamine, is a powerful inhibitor of mitochondrial function (Xie et al., 2013 ). ADD is able to induce mitochondrial dysfunction, resulting in the severe disruption of energy supply and inhibition of the ATP-dependent efflux transporter, P-gp, ultimately reversing MDR (Li et al., 2015 ; Qi et al., 2018 ; Wang et al., 2019 ). Several previous studies have demonstrated that the co-delivery of ADD and doxorubicin (DOX) effectively reverses MDR in breast cancer (Li et al., 2015 ; Qi et al., 2018 ; Wang et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…ADD is able to induce mitochondrial dysfunction, resulting in the severe disruption of energy supply and inhibition of the ATP-dependent efflux transporter, P-gp, ultimately reversing MDR (Li et al., 2015 ; Qi et al., 2018 ; Wang et al., 2019 ). Several previous studies have demonstrated that the co-delivery of ADD and doxorubicin (DOX) effectively reverses MDR in breast cancer (Li et al., 2015 ; Qi et al., 2018 ; Wang et al., 2019 ). It has also been reported that the co-delivery of two drugs, at an optimized ratio, and with rapidly and completely intracellular drug release, can achieve best therapeutic effects (Xiaopin et al., 2013 ; Yang et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…It has also been reported that the co-delivery of two drugs, at an optimized ratio, and with rapidly and completely intracellular drug release, can achieve best therapeutic effects (Xiaopin et al., 2013 ; Yang et al., 2019 ). A previous report solved the problem of co-delivering ADD and DOX at an optimal ratio by utilizing a pH-sensitive prodrug nanosystem (Wang et al., 2019 ). However, the total amount of DOX that was released within 72 h at pH 5.0 was lower than 30%.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Adjudin-loaded redox-sensitive paclitaxel-prodrug micelles for overcoming multidrug resistance with efficient targeted Colon cancer therapy

Chen

Zuo

et al. 2020

Drug Delivery

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Multidrug resistance (MDR) is the primary cause for the failure of chemotherapy in the treatment of colon cancer. Recent research has indicated that the combination of a chemotherapeutic agent and a mitochondrial inhibitor might represent a promising strategy to help overcome MDR. However, for this approach to be clinically effective, it is important that the two drugs can be actively and simultaneously delivered into tumor cells at an optimal ratio and completely released drug within cells. To address these challenges, we designed and prepared a folate receptor-targeted and redox-responsive drug delivery system (FA-ss-P/A) that was able to co-deliver paclitaxel (PTX) and adjudin (ADD) to reverse colon cancer MDR. The PTX prodrug was obtained by conjugating PTX to dextrin via a disulfide-linkage. Then, folic acid (FA) was modified on the PTX prodrug. Finally, ADD, a mitochondrial inhibitor, was encapsulated in the PTX prodrug-formed micelles. A series of in vitro and in vivo experiments subsequently demonstrated that FA-ss-P/A can effectively reverse MDR by increasing cell uptake, inhibiting PTX efflux, and improving drug release.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adjudin-loaded redox-sensitive paclitaxel-prodrug micelles for overcoming multidrug resistance with efficient targeted Colon cancer therapy

Chen

Zuo

et al. 2020

Drug Delivery

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show abstract

“…The range of pH values in inclusion bodies and lysosomes of tumor cells is 5.0-6.5, and that of tumor microenvironment is 6.5-7.2 [35]. PH-sensitive NPs can retain drug during humoral circulation and actively release drug around the tumor site or in lysosomes of tumor cells [36]. Therefore, we believe that the RGD-PDA-PHBV-PTX-NPs can remarkably reduce the potential damage to normal cells.…”

Section: Ph-sensitive Drug Release In Vitromentioning

confidence: 97%

pH-responsive delivery vehicle based on RGD-modified polydopamine-paclitaxel-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles for targeted therapy in hepatocellular carcinoma

Chen

Zhang

et al. 2021

J Nanobiotechnol

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A limitation of current anticancer nanocarriers is the contradiction between multiple functions and favorable biocompatibility. Thus, we aimed to develop a compatible drug delivery system loaded with paclitaxel (PTX) for hepatocellular carcinoma (HCC) therapy. A basic backbone, PTX-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) PHBV nanoparticle (PHBV-PTX-NPs), was prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine (PDA). The HCC-targeted arginine-glycine-aspartic acid (RGD)-peptide and PDA-coated nanoparticles (NPs) were combined through the Michael addition. Subsequently, the physicochemical properties of RGD-PDA-PHBV-PTX-NPs were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray spectroscopy. As expected, the RGD-PDA-PHBV-PTX-NPs showed robust anticancer efficacy in a xenograft mouse model. More importantly, they exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. Taken together, these results indicate that the RGD-PDA-PHBV-PTX-NPs are potentially beneficial for easing conflict between multifunction and biocompatible characters of nanocarriers.

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Nanomedicines for combating multidrug resistance of cancer

Zhu

Jia

Duan

et al. 2021

WIREs Nanomed Nanobiotechnol

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Chemotherapy typically involves the use of specific chemodrugs to inhibit the proliferation of cancer cells, but the frequent emergence of a variety of multidrug‐resistant cancer cells poses a tremendous threat to our combat against cancer. The fundamental causes of multidrug resistance (MDR) have been studied for decades, and can be generally classified into two types: one is associated with the activation of diverse drug efflux pumps, which are responsible for translocating intracellular drug molecules out of the cells; the other is linked with some non‐efflux pump‐related mechanisms, such as antiapoptotic defense, enhanced DNA repair ability, and powerful antioxidant systems. To overcome MDR, intense efforts have been made to develop synergistic therapeutic strategies by introducing MDR inhibitors or combining chemotherapy with other therapeutic modalities, such as phototherapy, gene therapy, and gas therapy, in the hope that the drug‐resistant cells can be sensitized toward chemotherapeutics. In particular, nanotechnology‐based drug delivery platforms have shown the potential to integrate multiple therapeutic agents into one system. In this review, the focus was on the recent development of nanostrategies aiming to enhance the efficiency of chemotherapy and overcome the MDR of cancer in a synergistic manner. Different combinatorial strategies are introduced in detail and the advantages as well as underlying mechanisms of why these strategies can counteract MDR are discussed. This review is expected to shed new light on the design of advanced nanomedicines from the angle of materials and to deepen our understanding of MDR for the development of more effective anticancer strategies. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

show abstract

Doxorubicin and adjudin co-loaded pH-sensitive nanoparticles for the treatment of drug-resistant cancer

Cited by 47 publications

References 49 publications

Adjudin-loaded redox-sensitive paclitaxel-prodrug micelles for overcoming multidrug resistance with efficient targeted Colon cancer therapy

Adjudin-loaded redox-sensitive paclitaxel-prodrug micelles for overcoming multidrug resistance with efficient targeted Colon cancer therapy

pH-responsive delivery vehicle based on RGD-modified polydopamine-paclitaxel-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles for targeted therapy in hepatocellular carcinoma

Nanomedicines for combating multidrug resistance of cancer

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