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Wang H, Moon C, Shin MC, et al. Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy. Nanotheranostics. 2017;1(1):114-130doi: 10.7150/ntno.18292.
Wang, H., Moon, C., Shin, M. C., Wang, Y., He, H., Yang, V. C., & Huang, Y. (2017). Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy. Nanotheranostics, 1(1), 114-130. https://doi.org/10.7150/ntno.18292
Wang, Huiyuan, et al. "Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy." Nanotheranostics vol. 1,1 (2017): 114-130. doi: https://doi.org/10.7150/ntno.18292
Wang H, Moon C, Shin MC, Wang Y, He H, Yang VC, Huang Y. Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy. Nanotheranostics. 2017 Mar 03;1(1):114-130. doi: 10.7150/ntno.18292. eCollection 2017. PMID: 29071181; PMCID: PMC5646728.
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Nanotheranostics. 2017 Mar 03;1(1):114-130. doi: 10.7150/ntno.18292. eCollection 2017.

Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy.

Nanotheranostics

Huiyuan Wang, Cheol Moon, Meong Cheol Shin, Yaping Wang, Huining He, Victor C Yang, Yongzhuo Huang

Affiliations

  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  2. College of Pharmacy, Sunchon National University, Republic of Korea.
  3. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Gyeongnam, Republic of Korea.
  4. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University Tianjin 300070, China.
  5. University of Michigan, College of Pharmacy, MI 48109-1065, USA.

PMID: 29071181 PMCID: PMC5646728 DOI: 10.7150/ntno.18292

Abstract

Heparin is a kind of naturally occurring polymer with excellent biocompatibility and solubility. It is characterized by dense of negative charge, higher than any endogenous components. Heparin can bind with various cationic peptides and proteins, thereby providing a useful noncovalent linkage for building a drug delivery system. As a case in point, heparin/cell-penetrating peptides (CPP) interaction is strong, and remains stable in vivo. They can be used to modify different proteins, respectively, and subsequently, by simply mixing the modified proteins, a protein-protein conjugate can be form via the stable heparin/CPP linkage. This linkage could not be broken unless addition of protamine that bears higher cationic charge density than CPP, and CPP thus can be substituted and released. Of note, heparin is a potent antagonist of CPP, and their binding naturally inhibits CPP-mediated drug cell penetration. Based on this method, we developed a heparin-regulated macromolecular prodrug-type system, termed ATTEMPTS, for drug targeting delivery. In this review article, we mainly summary the application of ATTEMPTS in delivery of various macromolecular drugs for cancer therapy, and also introduce the heparin-regulated nanoprobes for tumor imaging.

Keywords: Heparin; drug targeting delivery; heparin-regulated macromolecular prodrug-type system

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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