Beyond receptor expression levels: The relevance of target accessibility in ligand-directed pharmacodelivery systems

被引:37
|
作者
Ozawa, Michael G.
Zurita, Amado J.
Dias-Neto, Emmanuel
Nunes, Diana N.
Sidman, Richard L. [3 ,4 ]
Gelovani, Juri G. [2 ]
Arap, Wadih [1 ]
Pasqualini, Renata [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/j.tcm.2008.03.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
For development of a new ligand-directed pharmacology, it is critical to measure delivery of targeted drug ligands via molecular imaging or diagnostic readouts (termed theranostics). Combinatorial peptide libraries serve as unbiased functional screens that can identify specific peptides targeting cell-surface receptors accessible to the circulation. As candidate drug leads, such peptides provide motifs likely to modify ligand-receptor interactions and downstream signal transduction pathways. This strategy is synergistic with genomic and proteomic approaches and has yielded insights into the specialized nature of the target tissue microenvironment. However, for this vision to be realized, one must look, as recent literature suggests, beyond receptor levels and critically analyze ligand accessibility as a key determinant in pharmacodelivery systems.
引用
收藏
页码:126 / 133
页数:8
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