Disulfide-Cleavage-Triggered Chemosensors and Their Biological Applications

Lee, Min Hee; Yang, Zhigang; Lim, Choon Woo; Lee, Yun Hak; Dongbang, Sun; Kang, Chulhun; Kim, Jong Seung

doi:10.1021/cr300358b

Cited by 739 publications

(556 citation statements)

References 139 publications

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“…It has reported that the intracellular concentration of GSH, especially for the tumor cells, is 0.5-10 mM, which is far higher than blood and extracellular matrix (2-20 µM). 29 As shown in Figure 3A, no micellar size change was observed during incubated with 10 µM GSH. After incubated with 2 mM GSH, micellar size turned wider and remained about 100 nm.…”

Section: In Vitro Redox-responsive Behaviorsmentioning

confidence: 79%

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

Zhou¹,

Wang²,

Ying³

et al. 2017

IJN

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Multidrug resistance (MDR) against chemotherapeutic agents has become one of the major obstacles to successful cancer therapy and MDR-associated proteins (MRPs)-mediated drug efflux is the key factor for MDR. In this study, a redox-responsive polymer based on dextran (DEX) and indomethacin (IND), which could reduce MRPs-mediated efflux of chemotherapeutics, was synthesized, and the obtained polymer could spontaneously form stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 50 nm and effectively encapsulate doxorubicin (DOX); the micelles contain a disulfide bridge (cystamine, SS) between IND and DEX (DEX-SS-IND). In vitro drug release results indicated that DEX-SS-IND/DOX micelles could maintain good stability in a stimulated normal physiological environment and promptly depolymerized and released DOX in a reducing environment. After incubating DEX-SS-IND/DOX micelles with drug-resistant tumor (MCF-7/ADR) cells, the intracellular accumulation and retention of DOX were significantly increased under the synergistic effects of redox-responsive delivery and the inhibitory effect of IND on MRPs. In vitro cytotoxicity showed that DEX-SS-IND/DOX micelles exhibited higher cytotoxicity against MCF-7/ADR cells. Moreover, DEX-SS-IND/DOX micelles showed significantly enhanced inhibition of tumor in BALB/c nude mice bearing MCF-7/ADR tumors and reduced systemic toxicity. Overall, the cumulative evidence indicates that DEX-SS-IND/DOX micelles hold significant promise for overcoming MDR for cancer therapy.

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Section: In Vitro Redox-responsive Behaviorsmentioning

confidence: 79%

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

Zhou¹,

Wang²,

Ying³

et al. 2017

IJN

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“…The interesting progress has been made in disulfide-based cleavage systems in thiol detection connected with biological applications [112]. The disulfide cleavage reactions have a great impact on chemical sensing of drug delivery involved in the polymer and pharmaceutical chemistry.…”

Section: Fluorescent Dyes As "Molecular Photoswiches" and Molecular Cmentioning

confidence: 99%

“…Additionally, the cytotoxicity of drugs can be largely decreased by encapsulating them into polymer capsules. Such carriers improve the enhanced permeability retention effect (EPR) of the drugs [112]. The interesting example of self-assembly of molecular components into nanometer scale capsules with irreversible covalent bond formation using photoinitiated thiole-ene "click" reactions was reported by Kim et al [291].…”

Section: Stimulus Responsive Shell-tuning Capsules For Drug Deliverymentioning

confidence: 99%

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

Miksa¹

2016

Med chem (Los Angeles)

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This review highlights the role of fluorescent dyes as active "molecular photoswiches" focusing on the application in bioimaging and anticancer therapies in the field of therapeutic delivery. The author describes the development of prodrugs targeted to specific cell types and polymeric nanocarriers (capsules, micelles and silica nanoparticles) used as fluorescent probes which offer advantages in the integration of "smart" features of fluorescent dyes into synthetic materials. The incorporation of biologically responsive components that cleave upon changes in pH or light irradiation is fundamental to the successful design of such carriers with capabilities to load and release therapeutics specifically at a target site.

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“…Liquid chromatography-mass spectrometry analysis of the released products from mPEG-poly(TMC-CPT SS ) showed that the disulfide bond was cleaved by GSH ( Figure S15), which induced the breakdown of the neighboring carbonate bond to generate free CPT. [16] In contrast, only ~15% released drug was observed for mPEGpoly(TMC-CPT SS ) micelles when incubated without GSH. The nonresponsive control, mPEG-poly(TMCCPT O ) micelles also displayed slow drug release even upon addition of 10 mM GSH.…”

mentioning

confidence: 97%

Ring‐Opening Polymerization of Prodrugs: A Versatile Approach to Prepare Well‐Defined Drug‐Loaded Nanoparticles

Liu

Weitzhandler

et al. 2014

Angewandte Chemie

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We report a new methodology for the synthesis of polymer-drug conjugates from "compound"-all in one-prodrug monomers that consist of a cyclic polymerizable group that is appended to a drug through a cleavable linker. We show that organocatalyzed ring-opening polymerization can polymerize these monomers into well-defined polymer prodrugs that are designed to self-assemble into nanoparticles and release drug in response to a physiologically relevant stimulus. This method is compatible with structurally diverse drugs and allows different drugs to be copolymerized with quantitative conversion of the monomers. The drug loading can be controlled by adjusting the monomer(s) to initiator feed ratio and drug release can be encoded into the polymer by the choice of linker. Initiating these monomers from a polyethylene glycol macroinitiator yields amphiphilic diblock copolymers that spontaneously self-assemble into micelles with a long plasma circulation, which is useful for systemic therapy. KeywordsPolymerizable prodrug; Ring-opening polymerization; Polymer-drug conjugate; Nanoparticle; Cancer therapy Most small-molecule drugs utilized in the clinic have poor bioavailability and suboptimal pharmacokinetics because of their hydrophobicity and low molecular weight. Polymeric drug delivery systems can improve the efficacy of these drugs by increasing their water solubility, prolonging their circulation time, increasing the amount of drug deposited in the target tissue, and decreasing their exposure to normal tissues. [1] Conjugation of hydrophobic drugs to hydrophilic polymers can address these problems, [2] and is typically carried out by separate synthesis of the polymer, drug and linker, and sequential conjugation of the three entities to create the polymer-drug conjugate. This conventional strategy requires multiple reaction steps with limited yield, and has limited control of the site and degree of drug loading. New methods are hence needed to synthesize polymer-drug conjugates that have the following attributes: (1) are compatible with a structurally diverse set of drugs; (2) enable more than one drug to be conjugated to the same polymer with tunable control of the * chilkoti@duke.edu. Supporting information for this article is given via a link at the end of the document. Motivated by this rationale, we report herein a new method to synthesize polymer-drug conjugates by living ring-opening polymerization (ROP) of prodrugs (Scheme 1). This scheme inverts the conventional approach of conjugating a drug to a polymer post-synthesis, and instead directly incorporates the drug during synthesis of the polymer. These polymer prodrugs are composed of a "compound" monomer that consists of three covalently linked moieties: (1) a cyclic group that can undergo ROP to yield a biodegradable main chain, that is attached to (2) a cleavable linker, and which is attached to (3) a drug of interest. Living ROP of the compound monomer leads to the synthesis of a polymer with a biodegradable main chain with pendant drug molecules th...

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Disulfide-Cleavage-Triggered Chemosensors and Their Biological Applications

Cited by 739 publications

References 139 publications

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

Ring‐Opening Polymerization of Prodrugs: A Versatile Approach to Prepare Well‐Defined Drug‐Loaded Nanoparticles

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