Self-reinforced endocytoses of smart polypeptide nanogels for “on-demand” drug delivery

Ding, Jianxun; Xu, Weiguo; Zhang, Ying; Sun, Diankui; Xiao, Chunsheng; Liu, Donghong; Zhu, Xuemei; Chen, Xuesi

doi:10.1016/j.jconrel.2013.05.029

Cited by 102 publications

(87 citation statements)

References 47 publications

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“…This finding suggested that the reduction-triggered SS-M had a similar cellular uptake capacity to the non-SS-M counterpart but displayed more efficient intracellular drug release activity. 40,41 These results demonstrated that redox-sensitive micelles could improve the accumulation of Bru intracellularly, which could lead to higher cytotoxicity against cancer cells.…”

mentioning

confidence: 84%

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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mentioning

confidence: 84%

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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“…Subsequently, chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare TCAD@Ce6 nanoparticles (TCAD@Ce6 NPs), with TPGS as the hydrophilic shell, and chlorin e6 and DOX as the hydrophobic core. Thanks to the characteristic lower pH value present in tumor tissues and also in some intracellular vesicles as endosomes and lysosomes, 5,33 the acid-sensitive amide linker present in our TCAD@Ce6 nanoparticles acts as "OFF/ON" switch. Under ideal circumstances, our theranostic nanoparticles would not leak DOX and would self-quench the fluorescence of Ce6 by π-π interactions in blood circulation.…”

Section: 3mentioning

confidence: 99%

pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy

et al. 2016

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The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo-photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions ( pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo-photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo-photodynamic system for theranostics of lung cancer, etc. in the near future.

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“…[1][2][3] As the focus of attention, the intracellular components of tumor cells exhibit a more reductive condition in comparison with that outside cells. 4,5 In detail, the glutathione (GSH) concentration in cells (0.5−10.0 mM) is about three orders of magnitude higher than that outside cells (2.0−20.0 μM). [6][7][8][9] The potential difference of GSH concentration between extracellular region and intracellular organelles provides the possibility to design the reduction-responsive polymeric nanocarriers for selective intracellular drug delivery.…”

Section: Introductionmentioning

confidence: 99%

“…During the same period, that is, in the past decade, many other reduction-responsive nanogels have been investigated through thiol-disulfide exchange reaction, 18 Cu(I)-catalyzed "click chemistry" reaction, 19 quaternization reaction, 5 onestep ring-opening polymerization (ROP), 6,20,21 and so on. In this work, a reduction-responsive methoxy poly(ethylene glycol)−poly(l-phenylalanine-co-l-cystine) (mPEG−P(LPco-LC)) nanogel with facile preparation process and controllable performances was synthesized by our previously reported one-step ROP of l-phenylalanine N-carboxyanhydride (LP NCA) and l-cystine N-carboxyanhydride (LC NCA) with amino-terminated mPEG as a macroinitiator for targeting intracellular drug delivery in vivo (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model

Liu¹,

Wang²,

et al. 2015

IJN

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The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significantly higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of an antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1±3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was confirmed by the detection of body weight, histopathology, and biochemical indices of corresponding organs and serum. With controllable large-scale preparation and fascinating in vitro and in vivo properties, the reduction-responsive nanogel exhibited a good prospect for clinical chemotherapy.

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Self-reinforced endocytoses of smart polypeptide nanogels for “on-demand” drug delivery

Cited by 102 publications

References 47 publications

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

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

pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy

Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model

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Self-reinforced endocytoses of smart polypeptide nanogels for “on-demand” drug delivery

Cited by 102 publications

References 47 publications

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

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

pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy

Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in&nbsp;mouse model

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Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model