Acid Active Receptor-Specific Peptide Ligand for In Vivo Tumor-Targeted Delivery

Authors

  • Liang Han,

    1. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
    Search for more papers by this author
  • Yubo Guo,

    1. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
    Search for more papers by this author
  • Haojun Ma,

    1. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
    Search for more papers by this author
  • Xi He,

    1. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
    Search for more papers by this author
  • Yuyang Kuang,

    1. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
    Search for more papers by this author
  • Ning Zhang,

    1. In vivo Imaging R&D, Caliper Life Sciences, A Perkin Elmer Company, 2061 Challenger Drive, Alameda, CA 94501, USA
    Search for more papers by this author
  • Ed Lim,

    1. In vivo Imaging R&D, Caliper Life Sciences, A Perkin Elmer Company, 2061 Challenger Drive, Alameda, CA 94501, USA
    Search for more papers by this author
  • Wenjiang Zhou,

    1. Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
    Search for more papers by this author
  • Chen Jiang

    Corresponding author
    1. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
    • Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.

    Search for more papers by this author

Abstract

Targeting therapy of tumors in their early stages is crucial to increase the survival rate of cancer patients. Currently most drug-delivery systems target the neoplasia through the tumor-associated receptors overexpressed on the cancer cell membrane. However, the expression of these receptors on normal cells and tissues is inevitable, which leads to unwanted accumulation and side effects. Characteristics of the tumor microenvironment, such as acidosis, are pervasive in almost all solid tumors and can be easily accessed. It is shown that the different extracellular pH value can be used to activate/inactivate the receptor-mediated endocytosis on tumor/normal cells. This idea is implemented by conjugating a shielding molecule at the terminus of a receptor-specific ligand via a pH-sensitive hydrazone bond. The acid-activated detachment of the shielding molecule and enhanced tumor/background accumulation ratio are demonstrated. These results suggest that acid active receptor-specific peptide ligand-modified tumor-targeting delivery systems have potential use in the treatment of tumors.

Ancillary