Hypoxia-reinforced antitumor RNA interference mediated by micelleplexes with programmed disintegration

Li, Xudong; Xu, Xiangnan; Huang, Ke; Wu, Yuchen; Lin, Zhang; Yin, Lichen

doi:10.1016/j.actbio.2022.05.050

Cited by 9 publications

(12 citation statements)

References 64 publications

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“…Azobenzene-based material was applied to anticancer siRNA delivery and cooperated with PDT to eradicate tumor cells. Li et al constructed siRNA delivery micelleplexes (MPs) by assembling acid-transformable diblock copolymer PPDHP, AZO-cross-linked oligoethylenimine (AO), and siRNA against XIAP (siXIAP) . After internalization into cancer cells, PPDHP can be triggered by the endolysosomal acidity to expose AO.…”

Section: Utilizing Hypoxiamentioning

confidence: 99%

“…Li et al constructed siRNA delivery micelleplexes (MPs) by assembling acid-transformable diblock copolymer PPDHP, AZO-cross-linked oligoethylenimine (AO), and siRNA against XIAP (siXIAP). 332 After internalization into cancer cells, PPDHP can be triggered by the endolysosomal acidity to expose AO. Then, AO can be induced to degrade into lowmolecular weight segments under PDT-enhanced hypoxia to release siXIAP, which can potentiate the XIAP silencing efficiency.…”

Section: Utilizing Hypoxiamentioning

confidence: 99%

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Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

Pan,

Liu,

Mou

et al. 2023

ACS Nano

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Cancer with a complex pathological process is a major disease to human welfare. Due to the imbalance between oxygen (O 2 ) supply and consumption, hypoxia is a natural characteristic of most solid tumors and an important obstacle for cancer therapy, which is closely related to tumor proliferation, metastasis, and invasion. Various strategies to exploit the feature of tumor hypoxia have been developed in the past decade, which can be used to alleviate tumor hypoxia, or utilize the hypoxia for targeted delivery and diagnostic imaging. The strategies to alleviate tumor hypoxia include delivering O 2 , in situ O 2 generation, reprogramming the tumor vascular system, decreasing O 2 consumption, and inhibiting HIF-1 related pathways. On the other side, hypoxia can also be utilized for hypoxia-responsive chemical construction and hypoxia-active prodrug-based strategies. Taking advantage of hypoxia in the tumor region, a number of methods have been applied to identify and keep track of changes in tumor hypoxia. Herein, we thoroughly review the recent progress of nanomedicine strategies in both conquering and utilizing hypoxia to combat cancer and put forward the prospect of emerging nanomaterials for future clinical transformation, which hopes to provide perspectives in nanomaterials design.

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Section: Utilizing Hypoxiamentioning

confidence: 99%

Section: Utilizing Hypoxiamentioning

confidence: 99%

Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

Pan,

Liu,

Mou

et al. 2023

ACS Nano

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“…By comparison, spatially controlled siRNA activation is a feasible approach for tumor-specific siRNA therapy without unwanted gene inhibition in normal cells, because siRNA escaping from the endo-lysosome and releasing into the cytoplasm can be spatially controlled by responding to external and internal stimuli. [22][23][24] To achieve spatial siRNA activation, siRNA should be degraded in the normal cells but keep its activity in the tumor cells. However, few existing nanocarriers can meet these requirements.…”

Section: Research Articlementioning

confidence: 99%

“…Furthermore, the ROS generated by NIR irradiation were also capable to work for PDT which was combined with siRNA drug for synergistic antitumor therapy. [43][44][45] Therefore, the co-delivery of siRNAs and PSs using the quaternary ammonium group-based cationic polymers is in favor of achieving three aims: i) siRNA degradation in the normal cells; ii) spatially controlled siRNA activation in the tumor cells; iii) synergistic antitumor therapy.…”

Section: Research Articlementioning

confidence: 99%

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Unprotonatable and ROS‐Sensitive Nanocarrier for NIR Spatially Activated siRNA Therapy with Synergistic Drug Effect

Deng

Wang

Xiao

et al. 2022

Small

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Although small interfering RNA (siRNA) therapy has achieved great progress, unwanted gene inhibition in normal tissues severely limits its extensive clinical applications due to uncontrolled siRNA biodistribution. Herein, a spatially controlled siRNA activation strategy is developed to achieve tumor‐specific siRNA therapy without gene inhibition in the normal tissues. The quaternary ammonium moieties are conjugated to amphiphilic copolymers via reactive oxygen species (ROS)‐sensitive thioketal (TK) linkers for co‐delivery of siRNA and photosensitizer chlorin e6 (Ce6), showing excellent siRNA complexation capacity and near infrared (NIR)‐controlled siRNA release. In the normal tissue, siRNAs are trapped and degraded in the endo‐lysosomes due to the unprotonatable property of quaternary ammonium moiety, showing the siRNA activity “off” state. When NIR irradiation is spatially applied to the tumor tissue, the NIR irradiation/Ce6‐induced ROS trigger siRNA endo‐lysosomal escape and cytosolic release through the photochemical internalization effect and cleavage of TK bonds, respectively, showing the siRNA activity “on” state. The siRNA‐mediated glutathione peroxidase 4 gene inhibition enhances ROS accumulation. The synergistic antitumor activity of Ce6 photodynamic therapy and gene inhibition is confirmed in vivo. Spatially controlled tumor‐specific siRNA activation and co‐delivery with Ce6 using unprotonatable and ROS‐sensitive cationic nanocarriers provide a feasible strategy for tumor‐specific siRNA therapy with synergistic drug effects.

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Hypoxia‐Responsive Tetrameric Supramolecular Polypeptide Nanoprodrugs for Combination Therapy

Ding,

Yu,

Shen

et al. 2023

Adv Healthcare Materials

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Despite the intense progress of photodynamic and chemotherapy, however they cannot prevent solid tumor invasion, metastasis and relapse, along with inferior efficacy and severe side effect. The hypoxia‐responsive nanoprodrugs integrating photodynamic functions have been highly sought to address the above‐mentioned problems and overcome the tumor hypoxia‐reduced efficacy. Herein, a hypoxia‐responsive tetrameric supramolecular polypeptide nanoprodrug (SPN‐TAPP‐PCB4) was constructed from the self‐assembly of tetrameric porphyrin‐central poly(L‐lysine‐azobenzene‐chlorambucil) (TAPP‐(PLL‐Azo‐CB)4) and an anionic water‐soluble [2]biphenyl‐extended‐pillar[6]arene (AWBpP6) via the synergy of hydrophobic, π‐π stacking, and host‐guest interactions. Upon laser irradiation, the central TAPP could convert oxygen to generate single oxygen (1O2) to kill tumor cells. Furthermore, under the acidic and PDT‐aggravated hypoxia tumor cell microenvironment, SPN‐TAPP‐PCB4 was rapidly disassembled, and then efficiently released activated CB through the hypoxic‐responsive cleavage of azobenzene linkages. Both in vitro and in vivo biological studies showcased synergistic cancer‐killing actions between photodynamic therapy (PDT) and chemotherapy (CT) with negligible toxicity. Consequently, this supramolecular polypeptide nanoprodrug offers an effective strategy to design a hypoxia‐responsive nanoprodrug for potential combo PDT‐CT transition.This article is protected by copyright. All rights reserved

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Hypoxia-reinforced antitumor RNA interference mediated by micelleplexes with programmed disintegration

Cited by 9 publications

References 64 publications

Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

Unprotonatable and ROS‐Sensitive Nanocarrier for NIR Spatially Activated siRNA Therapy with Synergistic Drug Effect

Hypoxia‐Responsive Tetrameric Supramolecular Polypeptide Nanoprodrugs for Combination Therapy

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