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Acid Active Receptor‐Specific Peptide Ligand for In Vivo Tumor‐Targeted Delivery
Author(s) -
Han Liang,
Guo Yubo,
Ma Haojun,
He Xi,
Kuang Yuyang,
Zhang Ning,
Lim Ed,
Zhou Wenjiang,
Jiang Chen
Publication year - 2013
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201300279
Subject(s) - endocytosis , receptor , ligand (biochemistry) , cancer cell , drug delivery , tumor microenvironment , in vivo , biophysics , extracellular , cancer research , peptide , small molecule , chemistry , microbiology and biotechnology , cancer , biochemistry , biology , tumor cells , organic chemistry , genetics
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.