Uptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells

Yan, Yan; Johnston, Angus P. R.; Dodds, Sarah J.; Kamphuis, Marloes M. J.; Ferguson, Charles; Parton, Robert G.; Nice, Edouard C.; Heath, Joan K.; Caruso, Frank

doi:10.1021/nn100173h

Cited by 155 publications

(165 citation statements)

References 40 publications

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“…The inset shows a 3D reconstruction image of an apoptotic cell. As previously described, PMA SH capsules are assembled by subsequent cross-linking of the thiol groups [11]. The disulfide-bonded capsules are stable in oxidizing conditions (such as the bloodstream) but disassemble in reducing environments such as the cytoplasm of the cell [21].…”

Section: Resultsmentioning

confidence: 99%

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Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

Colone¹,

Kaliappan²,

Calcabrini³

et al. 2016

J Mol Genet Med

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The purpose of our study was to develop new delivery systems for drugs effective against breast cancer by using biodegradable and biocompatible capsules. Redox-active microcapsules based on thiolated polymethacrylic acid (PMA) were employed. The interaction of these PMA SH capsules with breast cancer cells and the mechanism of their internalization was investigated. PMA SH biocompatibility was evaluated by MTT assay. To analyze their potential as drug carrier, we incorporated doxorubicin into the capsules. Confocal microscopy observations showed the presence of capsules inside the cells. Although some drug molecules still appeared co-localized with PMA SH capsules, strong doxorubicin fluorescence was observed both in the cytoplasm and nucleus, indicating the disassembling of the capsule into PMA SH -drug conjugate after internalization. These results were confirmed by both flow cytometry (time course of capsule uptake) and scanning electron microscopy. PMA SH capsules were also internalized in 3D cell structures (spheroids) suggesting their potential use as drug delivery system for treatment of human diseases.

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Section: Resultsmentioning

confidence: 99%

“…conditions (such as the bloodstream) but to disassemble in reducing environments such as the cytoplasm of the cell [9][10][11][12]. The potential of PMA SH as an in vitro therapeutic delivery system of encapsulated proteins and peptides, oligonucleotides as well as small molecule drugs, has been demonstrated [13,14].…”

Section: Introductionmentioning

confidence: 99%

Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

Colone¹,

Kaliappan²,

Calcabrini³

et al. 2016

J Mol Genet Med

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“…39 103 . Therefore, the ability of nanocarriers to escape from endosomes is also critical for effective intracellular delivery and improved efficacy of protein therapeutics 124 .…”

Section: Discussionmentioning

confidence: 99%

Redox-responsive nanocapsules for intracellular protein delivery

et al. 2011

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Proteins play a crucial role in life, taking part in all vital processes in the body. Intracellular protein delivery holds enormous promise for biological and medical applications, including cancer therapy, vaccination, regenerative medicine, treatment for loss-of-function genetic diseases and imaging. Engineering vehicles for escorting therapeutic proteins into specific cells in a controlled release fashion has thus generated considerable interest. The development of such therapeutics to selectively target tumor has also been a major research focus in cancer nanotechnology. A novel strategy using polymeric redox-responsive nanocapsules for intracellular protein delivery is described, in which through in situ interfacial polymerization, the target therapeutic protein is noncovalently encapsulated into a biocompatible polymeric shell interconnected by disulfide-containing crosslinkers. The dissociation of the polymeric shell under reducing conditions and the subsequent release of protein were confirmed using cell-free assays in the presence of glutathione. Several therapeutic proteins with different properties, both cytosolic and nuclear, were successfully delivered using the platform. The nanocapsules were demonstrated to be efficiently internalized into mammalian cells through interactions between charge or targeting ligand, iii and to release the protein in the reducing cytosol in active forms. Using such redoxresponsive nanocapsule as a vehicle, pro-apoptotic protein caspase 3 was delivered to induce apoptosis in a variety of human cancer cell lines, including HeLa, MCF-7 and U-87 MG.Tumor-selective killer apoptin was delivered into different breast cancer cell lines as well, which led to rapid resurrection of apoptosis in breast cancer cell lines and shrinkage of xenograft mice models. Tumor suppressor p53 protein, the most commonly mutated protein, was also delivered selectively into tumor cells for apoptosis induction, through targeted redox-responsive nanocapsules. The delivery methodology is general, effective and nontoxic towards healthy cells. This work facilitate the development of new tools for tumorgenesis and drug resistance studies, as well as expanding current therapeutic target pool to many other tumor suppressor proteins for cancer treatment.iv The Dissertation of Muxun Zhao is approved.

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“…10 Disulfide-stabilized poly(methacrylic acid) capsules underwent lysosomal degradation by colon cancer cells. 11 However, latex particles of 500 nm in diameter were not localized in the lysosomal compartment in murine melanoma cell line B16-F10. 12 Thus, understanding the intracellular trafficking and fate of microspheres is important to design delivery system.…”

Section: Introductionmentioning

confidence: 96%

Cellular uptake and fate of fibroin microspheres loaded with randomly fragmented DNA in 3T3 cells

Lee

Hur

2016

IJN

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Purified fibroin protein can be obtained in large quantities from silk fibers and processed to form microscopic particles as delivery vehicles for therapeutic agents. In this study, we demonstrated that fibroin microspheres were taken up by 3T3 cells, localized in the nonlysosomal compartment, and secreted from the cytoplasm after medium replenishment. DNA-loaded microspheres were taken up by >95% of 3T3 cells. DNA cargo had no influence on the intracellular trafficking of microspheres, while fluorescently labeled cargo DNA was observed in the lysosomal compartment and in the microspheres. These results indicate that fibroin microspheres can travel through 3T3 cells without making any contact with the lysosomal compartments. The amount of DNA loaded in the microspheres taken up by 3T3 cells was estimated up to 831.0 pg/cell. Thus, fibroin microspheres can deliver a large amount of randomly fragmented DNA (<10 kb) into the cytoplasmic compartment of 3T3 cells.

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Uptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells

Cited by 155 publications

References 40 publications

Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

Redox-responsive nanocapsules for intracellular protein delivery

Cellular uptake and fate of fibroin microspheres loaded with randomly fragmented DNA in 3T3 cells

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Uptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells

Cited by 155 publications

References 40 publications

Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

Redox-responsive nanocapsules for intracellular protein delivery

Cellular uptake and fate of fibroin microspheres loaded with randomly fragmented DNA in 3T3&nbsp;cells

Contact Info

Product

Resources

About

Cellular uptake and fate of fibroin microspheres loaded with randomly fragmented DNA in 3T3 cells