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Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety

Paper ID Volume ID Publish Year Pages File Format Full-Text
223 17 2015 15 PDF Available
Title
Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety
Abstract

Chemotherapy plays an irreplaceable role in the treatment of various malignant tumors today. The traditional drug formulations lack of selectivity, cause serious damage to normal tissues, and can’t achieve a desired therapeutic efficacy. For this situation, a facilely prepared reduction-responsive polypeptide nanogel was employed for targeting intracellular delivery of antitumor drug in this study. Doxorubicin (DOX) as a model drug was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency (DLE) of 56.8 wt.%. The loading nanogel, i.e., NG/DOX, exhibited a medium hydrodynamic radius of 56.1 ± 3.5 nm, glutathione-accelerated DOX release, and efficient cellular uptake and proliferation inhibition. Moreover, NG/DOX exhibited upregulated intratumoral accumulation and improved antitumor efficacy toward HepG2 hepatoma-xenografted BALB/c nude mouse model compared with free drug. The enhanced tumor suppression of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was systematically demonstrated by the variation detection of body weight, histopathological assay, levels of bone marrow cell micronucleus rate (BMMR) and white blood cells (WBCs), and detection of clinical parameters in corresponding organs and serum. With controllable large-scale preparation and fascinating properties in vitro and in vivo, the reduction-responsive polypeptide nanogel is revealed to exhibit great potential for on-demand intracellular delivery of antitumor drugs, and shows a good prospect for clinical chemotherapy.Statement of SignificanceThe traditional drug formulations lack of selectivity, cause serious damage to normal tissues, and can’t achieve a desired therapeutic effect. For this situation, a facilely prepared reduction-responsive polypeptide nanogel is employed for targeting intracellular delivery of antitumor drug in this study. The laden nanogel keeps structural integrity and less drug release in the circulatory system after intravenous injection, releases the payload triggered by the intracellular high concentration of GSH, and exhibits the excellent tumor inhibition and security in vivo. Furthermore, the other hydrophobic antitumor drugs can also be on-demand delivered by the smart nanogel. All of the above advantages confirm the bright prospect of reduction-responsive nanogel on the road of malignancy chemotherapy.

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Keywords
Chemotherapy efficacy; Controlled release; Polypeptide nanogel; Reduction-responsiveness; Security
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Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 27, November 2015, Pages 179–193
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us