Disulfide bond based polymeric drug carriers for cancer chemotherapy and relevant redox environments in mammals

Zhang, Pei; Wu, Jilian; Xiao, Fengmei; Zhao, Dujuan; Luan, Yuxia

doi:10.1002/med.21485

Cited by 63 publications

(56 citation statements)

References 160 publications

(338 reference statements)

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“…According to the characteristics of tumor microenvironment, such as enzymes [12] and pH [13][14][15] differences, high reactive oxygen species (ROS) [16][17][18] and L-glutathione (GSH) [19] level, various stimuli-responsive nanocarriers have been designed. Of these aspects, as the GSH concentration of the malignant tissues is at least four-fold higher than that of the normal tissues [20][21][22], and the intracellular concentration of GSH is much higher than that in most extracellular fluids [23,24], many new GSH responsive nanoparticles achieved selective release of drugs at tumors [25]. However, most of them were prepared by complex process, such as modifying side groups [26].…”

Section: Introductionmentioning

confidence: 99%

A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy

et al. 2019

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The key to improve the therapeutic efficacy for cancer treatment is to increase the delivery of drugs to tumors. For this purpose, tumor-microenvironment stimuliresponsive materials have great potential. Here, we prepared a new nanomedicine by bonding the conjugate of honokiol (HNK) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to a glutathione (GSH)-responsive nanocarrier, poly(α-lipoic acid) polyethylene glycol. The nanomedicine would disintegrate due to the high level of GSH at the tumor sites, achieving the co-delivery of HNK and DMXAA, and realizing the combination therapy through close-range killing by HNK and long-range striking by DMXAA together. In a murine 4T1 breast tumor model, this strategy exhibited high tumor inhibition rate of 93%, and provided a valuable therapeutic choice for cancer therapy.

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Section: Introductionmentioning

confidence: 99%

A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy

et al. 2019

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“…The mammalian cell environment has different GSH concentrations between the extracellular fluids and intracellular spaces. Glutathione is a tripeptide consisting of glutamate, cysteine and glycine, with one reductive thiol group . The main function of GSH in vivo is to prevent damage from ROS .…”

Section: Carriers Regulated By the Tumor Microenvironmentmentioning

confidence: 99%

Tumor microenvironment as the “regulator” and “target” for gene therapy

Chen

Feng

et al. 2019

The Journal of Gene Medicine

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In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well‐designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non‐viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti‐cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli‐responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli‐responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the “regulator” and “target” when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.

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“…The micelles were disassembled only when the pH was lower than 6.8, indicating that the acidic environment was helpful for the release of doxorubicin. Furthermore, the disulfide bond in the structure of 15 was quickly cleaved by intracellular GSH, which could effectively accelerate drug release in the tumor site. It was found that more than 95% of doxorubicin was released in vitro from micelles after incubation for 48 hours in acidic medium containing 10 mM GSH.…”

Section: Applications Of Aie Probes In the Field Of Biological Sciencementioning

confidence: 99%

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

Guo

Song

et al. 2019

Medicinal Research Reviews

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Fluorescence imaging is a promising visualization tool and possesses the advantages of in situ response and facile operation; thus, it is widely exploited for bioassays. However, traditional fluorophores suffer from concentration limits because they are always quenched when they aggregate, which impedes applications, especially for trace analysis and real‐time monitoring. Recently, novel molecules with aggregation‐induced emission (AIE) characteristics were developed to solve the problems encountered when using traditional organic dyes, because these new molecules exhibit weak or even no fluorescence when they are in free movement states but emit intensely upon the restriction of intramolecular motions. Inspired by the excellent performances of AIE molecules, a substantial number of AIE‐based probes have been designed, synthesized, and applied to various fields to fulfill diverse detection tasks. According to numerous experiments, AIE probes are more practical than traditional fluorescent probes, especially when used in bioassays. To bridge bioimaging and materials engineering, this review provides a comprehensive understanding of the development of AIE bioprobes. It begins with a summary of mechanisms of the AIE phenomenon. Then, the strategies to realize accurate detection using AIE probes are discussed. In addition, typical examples of AIE‐active materials applied in diagnosis, treatment, and nanocarrier tracking are presented. In addition, some challenges are put forward to inspire more ideas in the promising field of AIE‐active materials.

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Disulfide bond based polymeric drug carriers for cancer chemotherapy and relevant redox environments in mammals

Cited by 63 publications

References 160 publications

A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy

A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy

Tumor microenvironment as the “regulator” and “target” for gene therapy

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

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