A Heparan Sulfate-Binding Cell Penetrating Peptide for Tumor Targeting and Migration Inhibition

Autor: Margaret Dah-Tsyr Chang, Ping-Hsueh Kuo, Chien-Jung Chen, Kang-Chiao Tsai, Pei-Lin Chang, Wen-Ching Wang, Yung-Jen Chuang
Rok vydání: 2015
Předmět:
Zdroj: BioMed Research International
BioMed Research International, Vol 2015 (2015)
ISSN: 2314-6141
2314-6133
Popis: As heparan sulfate proteoglycans (HSPGs) are known as co-receptors to interact with numerous growth factors and then modulate downstream biological activities, overexpression of HS/HSPG on cell surface acts as an increasingly reliable prognostic factor in tumor progression. Cell penetrating peptides (CPPs) are short-chain peptides developed as functionalized vectors for delivery approaches of impermeable agents. On cell surface negatively charged HS provides the initial attachment of basic CPPs by electrostatic interaction, leading to multiple cellular effects. Here a functional peptide (CPPecp) has been identified from critical HS binding region in hRNase3, a unique RNase family member within vitroantitumor activity. In this study we analyze a set of HS-binding CPPs derived from natural proteins including CPPecp. In addition to cellular binding and internalization, CPPecpdemonstrated multiple functions including strong binding activity to tumor cell surface with higher HS expression, significant inhibitory effects on cancer cell migration, and suppression of angiogenesisin vitroandin vivo. Moreover, different from conventional highly basic CPPs, CPPecpfacilitated magnetic nanoparticle to selectively target tumor sitein vivo. Therefore, CPPecpcould engage its capacity to be developed as biomaterials for diagnostic imaging agent, therapeutic supplement, or functionalized vector for drug delivery.
Databáze: OpenAIRE