title: Acid active receptor-specific peptide ligand for in vivo tumor-targeted delivery.
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.
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Liang
authors: L
authors: Han
authors: Yubo
authors: Y
authors: Guo
authors: Haojun
authors: H
authors: Ma
authors: Xi
authors: X
authors: He
authors: Yuyang
authors: Y
authors: Kuang
authors: Ning
authors: N
authors: Zhang
authors: Ed
authors: E
authors: Lim
authors: Wenjiang
authors: W
authors: Zhou
authors: Chen
authors: C
authors: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004705:Endocytosis; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010455:Peptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D010455:Peptides; D011956:Receptors, Cell Surface
keywords: acidity; cancer therapy; drug delivery; peptide ligands; receptors