Responsive Nanocarriers as an Emerging Platform for Cascaded Delivery of Nucleic Acids to Cancer

Liu, Yang; Xu, Cong; Iqbal, Shoaib; Yang, Xianzhu; Wang, Jun

doi:10.1016/j.addr.2017.03.004

Cited by 110 publications

(66 citation statements)

References 202 publications

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“…In addition, specific tumor stimuli-responsive DDSs, which respond to the characteristic biological stimuli that distinguish tumors from normal tissues, have been widely investigated to facilitate the precise delivery of chemotherapeutic agents to tumors 7,8 . Compared with normal cells, most tumor cells exhibit a redox-heterogeneous intracellular microenvironment due to the simultaneous overproduction of reactive oxygen species (ROS) and glutathione (GSH) 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Probing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy

et al. 2019

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Tumor cells are characterized as redox-heterogeneous intracellular microenvironment due to the simultaneous overproduction of reactive oxygen species and glutathione. Rational design of redox-responsive drug delivery systems is a promising prospect for efficient cancer therapy. Herein, six paclitaxel-citronellol conjugates are synthesized using either thioether bond, disulfide bond, selenoether bond, diselenide bond, carbon bond or carbon-carbon bond as linkages. These prodrugs can self-assemble into uniform nanoparticles with ultrahigh drug-loading capacity. Interestingly, sulfur/selenium/carbon bonds significantly affect the efficiency of prodrug nanoassemblies. The bond angles/dihedral angles impact the self-assembly, stability and pharmacokinetics. The redox-responsivity of sulfur/selenium/carbon bonds has remarkable influence on drug release and cytotoxicity. Moreover, selenoether/diselenide bond possess unique ability to produce reactive oxygen species, which further improve the cytotoxicity of these prodrugs. Our findings give deep insight into the impact of chemical linkages on prodrug nanoassemblies and provide strategies to the rational design of redox-responsive drug delivery systems for cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Probing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy

et al. 2019

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“…Third, PEI can become protonated in the acid environment of lysosomes, resulting in disassembly of PEI-Ap-EPI nanoparticles and promotion of DNA-duplex escape from lysosomes (23), which, ultimately, helps to enhance therapy efficacy. Fourth, the DNA duplex can have a negative charge, thereby impeding its internalization by cancer cells (24). Following interaction with PEI, the charge of the obtained nanoparticles changed to positive, which was conducive to cell internalization.…”

Section: Discussionmentioning

confidence: 99%

A facile adenosine triphosphate‑responsive nanoplatform for efficacious therapy of esophageal cancer

Wang

Liu

et al. 2020

Oncol Lett

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Current chemotherapeutic agents against esophageal cancer (EC) are suboptimal. To improve treatment efficacy, a nanoplatform based on ATP-responsive drug release was developed for EC therapy. First, the chemotherapeutic agent epirubicin (EPI) was inserted into an ATP aptamer (Ap) to form double-stranded DNA ('DNA duplex'). Subsequently, polyethyleneimine (PEI) was employed to condense the EPI-loaded duplex to construct the final nanoplatform (PEI-Ap-EPI). Following internalization by cancer cells, the EPI-loaded DNA duplex could open and release EPI in an intracellular ATP-rich environment. An in vitro drug-release assay demonstrated that ~50% of EPI was released from PEI-Ap-EPI in an ATP-rich condition. However, only 15% of EPI was released in the presence of a low concentration of ATP. In vitro cytotoxicity and apoptosis assays demonstrated that PEI-Ap-EPI could enhance EPI efficiency against EC cells markedly compared with those in the control group. Therefore, this facile PEI-Ap-EPI nanoplatform may be a promising strategy to improve the efficacy of EPI treatment in EC.

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“…16,17 The current challenge is to prompt efficient endosomal escape and improve the degradation of nanoparticles in the cytoplasm of cancer cells. 18,19 On the other hand, in view of the pH variation in tumor tissues (pH 6.5-6.9), endo/lysosomes (pH 5.0-5.5) and normal physiological environment (pH 7.4), [20][21][22] pHinduced charge-reversible nanoparticles have been extensively reported to spontaneously improve cellular uptake and controllable drug release through the enhanced permeability and retention effects. 23,24 The negative charge renders nanoparticles with stealth characteristics to avoid non-specific protein binding and prolong retention time.…”

Section: Introductionmentioning

confidence: 99%

<p>Cascade-Targeting of Charge-Reversal and Disulfide Bonds Shielding for Efficient DOX Delivery of Multistage Sensitive MSNs-COS-SS-CMC</p>

Cui¹,

Liu²,

Líu³

et al. 2020

IJN

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Responsive Nanocarriers as an Emerging Platform for Cascaded Delivery of Nucleic Acids to Cancer

Cited by 110 publications

References 202 publications

Probing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy

Probing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy

A facile adenosine triphosphate‑responsive nanoplatform for efficacious therapy of esophageal cancer

<p>Cascade-Targeting of Charge-Reversal and Disulfide Bonds Shielding for Efficient DOX Delivery of Multistage Sensitive MSNs-COS-SS-CMC</p>

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