Towards more accurate bioimaging of drug nanocarriers: turning aggregation-caused quenching into a useful tool

Qi, Jianping; Hu, Xiongwei; Dong, Xiaochun; Lü, Yi; Lu, Huiping; Zhao, Weili; Wu, Wei

doi:10.1016/j.addr.2019.05.009

Cited by 218 publications

(158 citation statements)

References 157 publications

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“…Conventional probes are frequently utilized to track the transport of NPs in cells, but they are limited by an inability to distinguish between NP‐encapsulated probe signals from the signals generated by released probes. [ 233 ] The ambiguous signals result in poor quantification of the NPs' intracellular delivery and impair the rational design of NPs. [ 234 ] In order to promote translation, it is critical to employ effective labeling strategies to clarify the fate of NPs in cells.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Metabolic cell‐labeling and ‐imaging by metabolic oligosaccharide engineering of unnatural carbohydrates may be effective in evaluating the cellular pharmacokinetics of NPs due to higher biocompatibility and specificity. [ 235 ] Alternatively, other environment‐responsive fluorescence probes based on aggregation‐caused quenching, [ 233,236 ] aggregation‐induced emission, [ 237 ] or förster resonance energy transfer [ 238 ] are a potential tool to quantify the NPs and accurately monitor their fate in cell models. In this article, we have explored the benefits of several intracellular delivery strategies as well as their limitations, particularly safety concerns and scalability.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Xing

Wang

et al. 2020

Adv Funct Materials

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125

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Biopharmaceuticals have emerged to play a vital role in disease treatment and have shown promise in the rapidly expanding pharmaceutical market due to their high specificity and potency. However, the delivery of these biologics is hindered by various physiological barriers, owing primarily to the poor cell membrane permeability, low stability, and increased size of biologic agents. Since many biological drugs are intended to function by interacting with intracellular targets, their delivery to intracellular targets is of high relevance. In this review, the authors summarize and discuss the use of nanocarriers for intracellular delivery of biopharmaceuticals via endosomal escape and, especially, the routes of direct cytosolic delivery by means including the caveolae‐mediated pathway, contact release, intermembrane transfer, membrane fusion, direct translocation, and membrane disruption. Strategies with high potential for translation are highlighted. Finally, the authors conclude with the clinical translation of promising carriers and future perspectives.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Xing

Wang

et al. 2020

Adv Funct Materials

Self Cite

125

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“…The formulations and administration doses based on the body weight are as follows: 1, saline; 2, CLG, 1 mg/kg; 3, CLG, 5 mg/kg; 4, CLG, 10 mg/kg; 5, CLG, 50 mg/kg; 6, CLG, 100 mg/kg; 7, PEI, 1 mg/kg; 8, PEI, 2.5 mg/kg; 9, PEI, 5 mg/kg. n = 3, *P < 0.05 and ***P < 0.001. keep their integrity up to 7-10 h (Lu et al, 2017;Qi et al, 2019). In this study, the BNRs with a payload capacity of 7-10-fold increase over conventional DDS entered cells via bypassing the endo-lysosomes and, as a result, maintained their integrity in the cytosol.…”

Section: Cellular Uptake Via Caveolar Pathwaymentioning

confidence: 66%

Deliver Anti-inflammatory Drug Baicalein to Macrophages by Using a Crystallization Strategy

Zhang

Teng

et al. 2020

Front. Chem.

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Macrophages are potent to modulate inflammation via phenotypic switch and production of inflammatory factors. Baicalein (BCL) is frequently used to alleviate inflammation; however, its application is always hindered due to low solubility. Herein, BCL nanocrystals (BNRs) were prepared to improve its delivery to macrophages. The prepared BNRs have a diameter of 150 nm with a rod-like structure. The nanocrystals could be well-taken up by macrophages via the caveolar pathway and, therefore, promote the polarization switch from proinflammatory phenotype to anti-inflammatory macrophages and alleviate the inflammation via reducing production cytokine IL-12. In conclusion, the crystallization strategy is promising for the improvement of the solubility of BCL and promotion of its anti-inflammatory activities.

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“…Addition of hydrophobic TCO group decreases aqueous solubility of Dox. We hypothesized that the reason for fluorescence quenching could be due to the local aggregation of Dox‐TCO‐NHS in aqueous media (ACQ) . Dox is poorly soluble in water and there have been efforts to increase Dox solubility either by liposomal encapsulation (Doxil: FDA‐approved nanodrug delivery system of Dox) or by chemical derivatization for higher dose administration.…”

Section: Resultsmentioning

confidence: 99%

Switchable Fluorescence of Doxorubicin for Label‐Free Imaging of Bioorthogonal Drug Release

Uyar

et al. 2020

ChemMedChem

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Monitoring the release and activation of prodrug formulations provides essential information about the outcome of a therapy. While the prodrug delivery can be confirmed by using different imaging techniques, confirming the release of active payload by using imaging is a challenge. Here, we have discovered that the switchable fluorescence of doxorubicin can validate drug release upon its uncaging reaction with a highly specific chemical partner. We have observed that the conjugation of doxorubicin with a trans‐cyclooctene (TCO) diminishes its fluorescence at 595 nm. This quenched fluorescence of the doxorubicin prodrug is recovered upon its bond‐cleaving reaction with tetrazine. Clinically assessed iron oxide nanoparticles were used to formulate a doxorubicin nanodrug. The release of doxorubicin from the nanodrug was studied under various experimental conditions. A fivefold increase in doxorubicin fluorescence is observed after complete release. The studies were carried out in vitro in MDA‐MB‐231 breast cancer cells. An increase in Dox signal was observed upon tetrazine administration. This switchable fluorescence mechanism of Dox could be employed for fundamental studies, that is, the reactivity of various tetrazine and TCO linker types under different experimental conditions. In addition, the system could be instrumental for translational research where the release and activation of doxorubicin prodrug payloads can be monitored by using optical imaging systems.

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Towards more accurate bioimaging of drug nanocarriers: turning aggregation-caused quenching into a useful tool

Cited by 218 publications

References 157 publications

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Deliver Anti-inflammatory Drug Baicalein to Macrophages by Using a Crystallization Strategy

Switchable Fluorescence of Doxorubicin for Label‐Free Imaging of Bioorthogonal Drug Release

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