Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety

Huang, Kexin; Shi, Bo; Xu, Weiguo; Ding, Jianxun; Yu, Yang; Liu, Haiyan; Zhuang, Xiuli; Chen, Xuesi

doi:10.1016/j.actbio.2015.08.049

Cited by 74 publications

(53 citation statements)

References 59 publications

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“…As shown in Figure 5g, compared with free AQ4N‐ and free DOX‐treated mice as controls, much stronger AQ4N/ZnPC (red) and DOX (green) fluorescence signals could be clearly observed inside the tumors of ZnPC‐ADMOP‐treated mice 4 h after intravenous injection, indicating better tumor accumulation of the nanosized drug. Free AQ4N and free DOX were mainly accumulated in the liver and lungs rather than in the tumor tissues, which was consistent with previous studies 37, 38, 39. However, it may be necessary to prolong the observation time to investigate the full drug metabolic process and the ultimate organ distribution in future studies.…”

Section: Resultssupporting

confidence: 90%

Chemotherapeutic Drug Based Metal–Organic Particles for Microvesicle‐Mediated Deep Penetration and Programmable pH/NIR/Hypoxia Activated Cancer Photochemotherapy

Zhang

Cai

et al. 2018

Advanced Science

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A novel metal–organic particle (MOP) based nanodrug formed by mild self‐assembly of chemotherapeutic drugs, including banoxantrone and doxorubicin, through Cu(II)‐mediated coordination effects, is reported. In this nanodrug, Cu(II) acts as a bridge to join AQ4N and DOX, and then, self‐assembly of [‐AQ4N‐Cu(II)‐(DOX)2‐Cu(II)‐]n complexes forms nanosized MOPs (referred to as ADMOPs) through multiple interactions including host–metal–guest coordination, hydrophobic interactions, π‐stacking, and van der Waals force. The ADMOPs reported here have several important features over conventional drugs, including tumor microenvironment pH‐sensitive drug release that can be tracked by “turning on” the fluorescence of AQ4N or DOX through proton competition with Cu(II) to break the coordination bonds and much deeper penetration into solid tumors via microvesicle‐mediated intercellular transfer. Most strikingly, the ADMOPs can serve as stimuli‐responsive nanocarriers to efficiently load the photosensitizer phthalocyanine due to their inherent highly porous characteristics. Thus, the ADMOPs significantly enhance the chemotherapeutic efficacy by “on‐demand” photodynamic therapy, which further induces a hypoxic environment that enhances the reduction of AQ4N to systematically increase the therapeutic efficiency. Taken together, the designed ADMOPs composed of chemotherapeutic drugs may serve as a potential programmable controlled synergistic agent for cancer therapy.

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Section: Resultssupporting

confidence: 90%

Chemotherapeutic Drug Based Metal–Organic Particles for Microvesicle‐Mediated Deep Penetration and Programmable pH/NIR/Hypoxia Activated Cancer Photochemotherapy

Zhang

Cai

et al. 2018

Advanced Science

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“…This was mainly due to the increased cellular uptake and accelerated drug release in the reductive environment of the cytoplasm. [42][43][44] Therefore, delivery via F68-SS-LA micelles could potentially improve the in vitro cytotoxicity of Bru.…”

Section: Cytotoxicity In Vitromentioning

confidence: 99%

Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol

Zhang¹,

Fang²,

Li³

et al. 2018

IJN

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Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic ® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1 H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway.

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“…Especially, disulfide crosslinking which is prone to cleavage in intracellular matrix containing high concentration of the reducing protein glutathione has been used to reversibly stabilize polymeric micelles or NPs (Chaurasiya, Mahanty, Roy, Shen, Tu & Sun, 2016;Rahimian, Wen & Oh, 2015;Wei et al, 2012;Wu, Zou, Deng, Cheng, Meng & Zhong, 2013). To form disulfide bonds, different crosslinkers, i.e., cystamine 3,3'-dithiobis(sulfosuccinimidylpropionate), N,N-bis(acryloyl)cystamine, cysteine N-carboxyanhy-dride (Cystine-NCA), oxidizing free thiol groups and lipoic acid (LA), have been investigated to achieve stabilization purpose (Dai, Lin, Cheng, Zou & Shuai, 2011;Huang et al, 2015;Lee, Kim, Tyler, Park & Cheng, 2013;Ru et al, 2011;Shen et al, 2015;Wang et al, 2010;Xing, Lai, Ye & Yan, 2011). Wei and Cheng et al, reported that LA could successfully crosslink the polymeric micelles via disulfide linkage (Wei et al, 2012;Zhong et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Efficient delivery of paclitaxel into ASGPR over-expressed cancer cells using reversibly stabilized multifunctional pullulan nanoparticles

Huang

Wang

Ling

et al. 2017

Carbohydrate Polymers

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Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety

Cited by 74 publications

References 59 publications

Chemotherapeutic Drug Based Metal–Organic Particles for Microvesicle‐Mediated Deep Penetration and Programmable pH/NIR/Hypoxia Activated Cancer Photochemotherapy

Chemotherapeutic Drug Based Metal–Organic Particles for Microvesicle‐Mediated Deep Penetration and Programmable pH/NIR/Hypoxia Activated Cancer Photochemotherapy

Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol

Efficient delivery of paclitaxel into ASGPR over-expressed cancer cells using reversibly stabilized multifunctional pullulan nanoparticles

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