Co-delivery of paclitaxel and doxorubicin using mixed micelles based on the redox sensitive prodrugs

Yang, Min; Ding, Houqiang; Zhu, Yixin; Ge, Yanxiu; Li, Lingbing

doi:10.1016/j.colsurfb.2018.11.086

Cited by 35 publications

(12 citation statements)

References 46 publications

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“…DOX is a cationic small-molecule drug that intercalates into nuclear DNA and thus induces apoptosis. PTX induces cell apoptosis by interfering with the normal functions of microtubules during cell mitosis (Wu et al., 2017 ; Zhao et al., 2017 ; Feng et al., 2019 ; Yang et al., 2019 ). The synergistic effects of DOX and PTX have been investigated in the treatment of breast cancer, lung cancer, melanoma, and hepatic carcinoma, however, their synergistic therapeutic efficacy against osteosarcoma has been poorly understood (Jin et al., 2010 ; Wang et al., 2011 , 2016 ; Zhao et al., 2011 , 2017 ; Liu et al., 2014 ; Baabur-Cohen et al., 2017 ; Qiu et al., 2017 ; Jiang et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy

Hou

Zhang

et al. 2020

Drug Delivery

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Nanoparticle-based drug delivery system offers a promising platform for combination cancer therapy. However, the inefficient drug release in cells reduces the therapeutic efficacy of cancer nanomedicines. Herein, a PEGylated poly(a-lipoic acid) copolymer (mPEG-PaLA) was prepared and used as a reduction/ pH dual responsive nanocarrier to simultaneously deliver paclitaxel (PTX) and doxorubicin (DOX) for osteosarcoma therapy. The amphiphilic mPEG-PaLA could efficiently encapsulate both PTX and DOX during its self-assembly into micelles in aqueous solution to generate PTX and DOX co-loaded nanoparticles (NP-PTX-DOX). The as-prepared NP-PTX-DOX showed enhanced PTX and DOX release in response to reductive and acidic stimuli. Moreover, the dual-drug loaded nanoparticles were efficiently internalized by K7 osteosarcoma cells and released drugs intracellularly, as confirmed by flow cytometry analysis and confocal laser scanning microscopy. Consequently, NP-PTX-DOX exhibited synergistic therapeutic effects and induced enhanced cell apoptosis in K7 cells. Furthermore, NP-PTX-DOX presented improved biodistribution and higher tumor growth inhibition efficacy compared to the control groups in a murine osteosarcoma model. Altogether, the results of this work indicate that the proposed strategy is promising for osteosarcoma therapy using mPEG-PaLA copolymer as a dual-responsive nanocarrier to co-deliver anticancer drugs.

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Section: Introductionmentioning

confidence: 99%

Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy

Hou

Zhang

et al. 2020

Drug Delivery

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“…Lately, a lot of efforts have been focused on the development of redox-responsive nanosystems. They could be of major interest in the treatment of cancer, as the reduction potential of cancer cells is higher than the reduction potential of healthy cells [ 2 ]. The release is then triggered in the tumor, minimizing the side effects.…”

Section: Introductionmentioning

confidence: 99%

Three-Step Synthesis of a Redox-Responsive Blend of PEG–block–PLA and PLA and Application to the Nanoencapsulation of Retinol

Gheluwe

Buchy²,

Chourpa

et al. 2020

Polymers

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Smart polymeric nanocarriers have been developed to deliver therapeutic agents directly to the intended site of action, with superior efficacy. Herein, a mixture of poly(lactide) (PLA) and redox-responsive poly(ethylene glycol)–block–poly(lactide) (PEG–block–PLA) containing a disulfide bond was synthesized in three steps. The nanoprecipitation method was used to prepare an aqueous suspension of polymeric nanocarriers with a hydrodynamic diameter close to 100 nm. Retinol, an anti-aging agent very common in cosmetics, was loaded into these smart nanocarriers as a model to measure their capacity to encapsulate and to protect a lipophilic active molecule. Retinol was encapsulated with a high efficiency with final loading close to 10% w/w. The stimuli-responsive behavior of these nanocarriers was demonstrated in vitro, in the presence of l-Glutathione, susceptible to break of disulfide bond. The toxicity was low on human keratinocytes in vitro and was mainly related to the active molecule. Those results show that it is not necessary to use 100% of smart copolymer in a nanosystem to obtain a triggered release of their content.

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“…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 ). 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 ).…”

Section: Introductionmentioning

confidence: 99%

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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Co-delivery of paclitaxel and doxorubicin using mixed micelles based on the redox sensitive prodrugs

Cited by 35 publications

References 46 publications

Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy

Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy

Three-Step Synthesis of a Redox-Responsive Blend of PEG–block–PLA and PLA and Application to the Nanoencapsulation of Retinol

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

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