Redox-Responsive Biomimetic Polymeric Micelle for Simultaneous Anticancer Drug Delivery and Aggregation-Induced Emission Active Imaging

Hu, Jun; Zhuang, Weihua; Ma, Boxuan; Su, Xin; Yu, Tao; Li, Gaocan; Hu, Yanfei; Wang, Yunbing

doi:10.1021/acs.bioconjchem.8b00119

Cited by 57 publications

(40 citation statements)

References 46 publications

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“…However, the particle size indicated by TEM was lower than that of differential light scattering (DLS), which was caused by polymer dehydration during TEM sample preparation. 33…”

Section: Resultsmentioning

confidence: 99%

Sialic acid–targeted drug delivery and imaging system for pH- and glutathione-triggered multiple anticancer drug release and enhanced oxidative stress

Peng

Zeng²,

et al. 2020

Journal of Bioactive and Compatible Polymers

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The emergence of multiple drug delivery systems can solve the disadvantages of single-drug therapy, such as high dose and easy generation of drug resistance. Here, we designed a sialic acid–targeted dextran-mercaptopurine prodrug linked by carbonyl vinyl sulfide for coordinate ZnO quantum dots to achieve multiple drug delivery (doxorubicin, 5-fluorouracil, 6-mercaptopurine), which can be released under the trigger of pH and glutathione. To enhance the antitumor effect, we used inorganic photosensitizer CdSe quantum dots to achieve photodynamic therapy, which can produce cytotoxic reactive oxygen species (hydroxyl radicals) under light conditions. Notably, we found that glutathione is consumed by the delivery of 6-mercaptopurine. It is able to efficiently amplify intracellular oxidative stress via increasing •OH generation. After chelating 99mTc4+ radioisotopes by diethylenetriamine pentaacetic acid, the drug delivery system could be tracked under in vivo single-photon emission computed tomography imaging. The results showed that the phenylboronic acid targeting substance can specifically recognize sialic acid, so that the drug system has a good accumulation in the tumor site, which can better increase the therapeutic effect. Compared to free doxorubicin, the drug system can reduce the IC50 value of cells 4.4-fold under light conditions and significantly inhibit tumor growth in vivo. These data indicate that the sialic acid–targeted nanomedicine system has achieved ideal antitumor effects and apparent photodynamic therapy effects and has broad application prospects.

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“…However, the particle size indicated by TEM was lower than that of differential light scattering (DLS), which was caused by polymer dehydration during TEM sample preparation. 33…”

Section: Resultsmentioning

confidence: 99%

Sialic acid–targeted drug delivery and imaging system for pH- and glutathione-triggered multiple anticancer drug release and enhanced oxidative stress

Peng

Zeng²,

et al. 2020

Journal of Bioactive and Compatible Polymers

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“…Hydrophobic drugs can be physically entrapped in or covalently bound to the core of the micelles . Recently, intelligent micelles have been designed to be stimulus‐sensitive, such as redox‐, temperature‐, pH‐ and specific enzyme‐dependent responses for targeted delivery . Zhuang et al developed a redox and pH dual‐responsive micelle system to deliver doxorubicin.…”

Section: Applications Of Aie Probes In the Field Of Biological Sciencementioning

confidence: 99%

“…143,144 Recently, intelligent micelles have been designed to be stimulus-sensitive, such as redox-, temperature-, pH-and specific enzyme-dependent responses for targeted delivery. 145,146 Zhuang et al 147 developed a redox and pH dual-responsive micelle system to deliver doxorubicin. They synthesized an amphiphilic polymer with AIE attributes (15, Figure 2) which can self-assemble into micelles.…”

Section: Organic Nps Tracked By Aiegensmentioning

confidence: 99%

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

Guo

Song

et al. 2019

Medicinal Research Reviews

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Fluorescence imaging is a promising visualization tool and possesses the advantages of in situ response and facile operation; thus, it is widely exploited for bioassays. However, traditional fluorophores suffer from concentration limits because they are always quenched when they aggregate, which impedes applications, especially for trace analysis and real‐time monitoring. Recently, novel molecules with aggregation‐induced emission (AIE) characteristics were developed to solve the problems encountered when using traditional organic dyes, because these new molecules exhibit weak or even no fluorescence when they are in free movement states but emit intensely upon the restriction of intramolecular motions. Inspired by the excellent performances of AIE molecules, a substantial number of AIE‐based probes have been designed, synthesized, and applied to various fields to fulfill diverse detection tasks. According to numerous experiments, AIE probes are more practical than traditional fluorescent probes, especially when used in bioassays. To bridge bioimaging and materials engineering, this review provides a comprehensive understanding of the development of AIE bioprobes. It begins with a summary of mechanisms of the AIE phenomenon. Then, the strategies to realize accurate detection using AIE probes are discussed. In addition, typical examples of AIE‐active materials applied in diagnosis, treatment, and nanocarrier tracking are presented. In addition, some challenges are put forward to inspire more ideas in the promising field of AIE‐active materials.

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“…The specific microenvironment of tumor makes it an available strategy for constructing stimuli triggered drug release, such as pH responsiveness 21-22 and redox responsiveness 23-24, which have been reported to improve antitumor efficacy. However, the antitumor effect of single pH response or redox response still needs ulteriorly improve 25-27. On the contrary, DDS with synergetic dual-response or multi-response have showed better antitumor effect, which would be suitable for designing smart DDS for theranostics 28-30.…”

Section: Introductionmentioning

confidence: 99%

Two-photon AIE luminogen labeled multifunctional polymeric micelles for theranostics

Zhuang¹,

Ma²,

Hu³

et al. 2019

Theranostics

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Intelligent polymeric micelles with fluorescence imaging feature have been emerged as promising tools for theranostics. However, conventional fluorescent dyes are limited by short wavelength excitation, interference of tissue autofluorescence, limited imaging depth and quenched emission in aggregation state.Methods: We synthesized a novel mPEG-SS-Poly (AEMA-co-TBIS) (mPEATss) copolymer to develop multifunctional polymeric micelles with great AIE feature for cancer therapy and AIE active two-photon bioimaging. The stimuli-responsive behavior and AIE active two-photon cell and tissue imaging as well as in vitro and in vivo antitumor ability of DOX-loaded mPEATss were studied.Results: mPEATss micelles showed excellent AIE active two-photon cell imaging ability and deep tissue imaging ability. Antitumor drug DOX could be encapsulated to form a drug-loaded micellar system with a small diameter of 65 nm. The disassembly and charge-conversion of mPEATss micelles could be triggered by acidic environment, resulting in accelerated drug release and great antitumor efficacy. In vivo, ex vivo imaging and in vivo pharmacokinetic study demonstrated that mPEATss micelles could efficiently accumulate in tumor sites, which ensured ideal anticancer effect.Conclusions: This pH and redox dual responsive and AIE active two-photon imaging polymeric micelles would be a promising candidate for theranostics.

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Redox-Responsive Biomimetic Polymeric Micelle for Simultaneous Anticancer Drug Delivery and Aggregation-Induced Emission Active Imaging

Cited by 57 publications

References 46 publications

Sialic acid–targeted drug delivery and imaging system for pH- and glutathione-triggered multiple anticancer drug release and enhanced oxidative stress

Sialic acid–targeted drug delivery and imaging system for pH- and glutathione-triggered multiple anticancer drug release and enhanced oxidative stress

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

Two-photon AIE luminogen labeled multifunctional polymeric micelles for theranostics

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