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Combining Systemic and Intracellular Delivery of Cytochrome C to Tumors by a Protein Nanocapsule with Tumor-Specific Cleavable PEG

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Systemic delivery of therapeutic proteins for cancer therapy remains an imperative challenge because it is hard to tackle the prolonging in vivo half-life and efficient intracellular delivery. To overcome this problem, we had developed a novel anticancer protein nanocapsule (nCytC-bPEG) by conjugating tumor-specific cleavable PEG to surface amine-containing CytC nanocapsule (nCytC) through a pH-responsive benzoic-imine bond. The dynamic light scattering (DLS) and transmission electron microcopy (TEM) investigations revealed that the obtained nCytC-bPEG was having spherical (ca. 25 nm) morphology. The zeta potential measurements indicated that nCytC-bPEG was electroneutral at pH 7.4, but it rapidly adopts cationic nature in acidic tumor environment. In vitro stability and release assays showed that nCytC-bPEG remains robust when treated with FBS and releases drug in GSH environment. Additionally, nCytC-bPEG had been proved to be effectively uptaken by the cancer cells in tumor environment due to the change in its surface charge after PEG cleavage and lead to severe cell cytotoxicity. Thus, the presented investigation offers an exquisite strategy for CytC to prolong circulation time and improve cellular delivery efficiency in clinical use.
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Keywords: BENZOIC-IMINE; CANCER THERAPY; CLEAVABLE PEG; CYTOCHROME C; NANOCAPSULES

Document Type: Research Article

Publication date: August 1, 2017

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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