Bioengineered Human Serum Albumin Fusion Protein as Target/Enzyme/pH Three-Stage Propulsive Drug Vehicle for Tumor Therapy

ACS Nano
Mingyu WangJinghua Chen

Abstract

Human serum albumin (HSA) has the characteristics of biocompatibility and long circulation, which is widely used as the carrier of insoluble anticancer drugs, but it also has some disadvantages such as weak tumor targeting and uncontrollable drug release. Herein, HSA was modified to improve its biological performance by introducing polyhistidine (pHis), matrix metalloproteinase-2 (MMP-2) digestion, and Arg-Gly-Asp (RGD) peptide at the separated end of HSA through gene fusion technology. The resulting protein expressed by Pichia pastoris could self-assemble into 3RGD-HSA-MMP-18His nanoparticles (RHMH18 NPs) accompanied by loading hydrophobic drug paclitaxel (PTX) into the polyhistidine micelle core. RHMH18 NPs exhibited active tumor targeting in high efficiency owing to the RGD-mediated specific binding toward ανβ3-integrin upregulated on tumor vasculature endothelium, resulting in the enrichment of therapeutic substances in tumor sites. Once reaching the tumor microenvironment, RHMH18 NPs was cut off by MMP-2 to remove the HSA-3RGD moiety, leaving the small and positively charged histidine micelle, which could penetrate the deep part of tumor tissue more effectively. Finally, the histidine micelle escaped from lysosome successf...Continue Reading

References

Jul 20, 2002·Current Opinion in Pharmacology·Gordon C Tucker
Jan 22, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adhiambo M WitloxWinald R Gerritsen
Feb 21, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Neil DesaiPatrick Soon-Shiong
Nov 30, 2006·European Journal of Nuclear Medicine and Molecular Imaging·Angelika von WallbrunnChristoph Bremer
Jun 28, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Felix Kratz
Jun 12, 2009·International Journal of Nanomedicine·Evelina MieleSilverio Tomao
Sep 13, 2012·Molecular Pharmaceutics·Fabienne DanhierVéronique Préat
Oct 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Minmin LiangXiyun Yan
Jan 31, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hyeong Jun ByeonYu Seok Youn
Apr 26, 2016·Advanced Materials·Qian Chen, Zhuang Liu
Nov 12, 2016·Nature Reviews. Cancer·Jinjun ShiOmid C Farokhzad
Mar 20, 2018·Drug Delivery·Jincheng YangYoujun Xu
May 21, 2019·Advanced Materials·Yazhong BuDecheng Wu
Jul 19, 2019·Journal of the American Chemical Society·Cassandra E CallmannNathan C Gianneschi
Sep 9, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jiuyang HeXiyun Yan

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.