A polymeric micelle with an endosomal pH-sensitivity for intracellular delivery and enhanced antitumor efficacy of hydroxycamptothecin

Pu, Xiaohui; Zhao, Luling; Li, Jia; Song, Ru-Feng; Wang, Yanling; Yu, Kejing; Hou, Xianqiao; Qiao, Panzhe; Zong, Lei; Sheng, Chang

doi:10.1016/j.actbio.2019.02.039

Cited by 41 publications

(24 citation statements)

References 52 publications

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“…2C shows the plasma stability of the polymer prodrug micelles. The particle sizes of PDSP and PDCP micelle did not change signi cantly for 48 h after being mixed with rat plasma, which suggests that they could remain stable when administered intravenously [32].…”

Section: Stability Of Micellesmentioning

confidence: 95%

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Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Zong

et al. 2021

Preprint

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Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug-resistance as a carrier to overcome MDR and improve the anti-tumor effect of paclitaxel (PTX). The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells, and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of DOX to H22 subcutaneous tumor-bearing mice. This work proves the reduction sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.

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Section: Stability Of Micellesmentioning

confidence: 95%

“…After that, the tumor was weighed, and all tissues were buried in wax and sliced to perform hematoxylin and eosin (H&E) staining for pathology. The tumor weight and volume inhibition ratio (IR w and IR v ) were calculated using the following formula [32]:…”

Section: In Vivo Antitumor Activitymentioning

confidence: 99%

Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Zong

et al. 2021

Preprint

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“…The PDCP and PDSP micelles were prepared by the film dispersion method. 29 20 mg of PDCP was dissolved in 10 mL of CH 2 Cl 2 through stirring. After complete dissolution, CH 2 Cl 2 was removed to form films of the polymer prodrug by rotary evaporation, which were then dried overnight under vacuum.…”

Section: Methodsmentioning

confidence: 99%

Two-Pronged Anti-Tumor Therapy by a New Polymer-Paclitaxel Conjugate Micelle with an Anti-Multidrug Resistance Effect

Du¹,

Zong²,

Li³

et al. 2022

IJN

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“…Nowadays, multifunctional nanomedicine integrating various modules of targeting ( Qiao et al, 2019 ), lysosomal escaping, stimuli sensitivity, etc. ( Pu et al, 2019 ; Zong et al, 2020 ; Zhong et al, 2021 ; Zong et al, 2021 ) could further improve the drug delivery efficacy, maximizing the therapeutic outcomes ( Chen et al, 2017 ; Shahriari et al, 2019 ; Yang et al, 2019 ; He et al, 2021 ; Peng et al, 2021 ). It should be noted that the mitochondrial-targeting strategy plays an essential role in fully taking advantage of LND ( Li et al, 2013 ; Zhang et al, 2015 ; Liu et al, 2017 ; Guo et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Targeting and pH-Responsive Nanogels for Co-Delivery of Lonidamine and Paclitaxel to Conquer Drug Resistance

Chen

Wang

Zhang

et al. 2021

Front. Bioeng. Biotechnol.

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Multidrug resistance (MDR) is one of the leading causes of the failure of cancer chemotherapy and mainly attributed to the overexpression of drug efflux transporters in cancer cells, which is dependent on adenosine triphosphate (ATP). To overcome this phenomenon, herein, a mitochondrial-directed pH-sensitive polyvinyl alcohol (PVA) nanogel incorporating the hexokinase inhibitor lonidamine (LND) and the chemotherapeutic drug paclitaxel (PTX) was developed to restore the activity of PTX and synergistically treat drug-resistant tumors. The introduction of 2-dimethylaminoethanethiol (DMA) moiety into the nanogels not only promoted the drug loading capacity but also enabled the lysosomal escape of the nanogels. The subsequent mitochondrial targeting facilitated the accumulation and acid-triggered payload release in the mitochondria. The released LND can destroy the mitochondria by exhausting the mitochondrial membrane potential (MMP), generating reactive oxygen species (ROS) and restraining the energy supply, resulting in apoptosis and susceptibility of the MCF-7/MDR cells to PTX. Hence, the nanogel-enabled combination regimen of LND and PTX showed a boosted anti-tumor efficacy in MCF-7/MDR cells. These mitochondrial-directed pH-sensitive PVA nanogels incorporating both PTX and LND represent a new nanoplatform for MDR reversal and enhanced therapeutic efficacy.

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A polymeric micelle with an endosomal pH-sensitivity for intracellular delivery and enhanced antitumor efficacy of hydroxycamptothecin

Cited by 41 publications

References 52 publications

Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Two-Pronged Anti-Tumor Therapy by a New Polymer-Paclitaxel Conjugate Micelle with an Anti-Multidrug Resistance Effect

Mitochondrial Targeting and pH-Responsive Nanogels for Co-Delivery of Lonidamine and Paclitaxel to Conquer Drug Resistance

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