Fluorescent RGD-based pro-apoptotic peptide conjugates as mitochondria-targeting probes for enhanced anticancer
Syed Faheem Askari Rizvi1, Shuai Mu1, Yaya Wang1
1State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China.
Abstract:
We have designed 2-domain anticancer peptides with RGD-based KLAK bi-functional short motifs (linear and cyclic analogues). RGD tripeptide acts as tumor blood vessel 'homing' motif while KLAK tetrapeptide internalized in mitochondria and causes cell apoptosis. All three peptides (RGDKLAK; HM, cyclic-RGDKLAK; HMC-1, and RGD-cyclic-KLAK; HMC-2) were conjugated with fluorescein isothiocyanate isomer-I (5-FITC; F) for in-vivo and in-vitro optical imaging studies. These fluorescent-peptide (FL-peptide) analogues were analyzed to possess αvβ3-integrin targeting affinity, high uptake in in-vitro cell binding assays followed by in-vivo tumor xenograft mice studies. Pharmacological profile reveals that F-HMC-1 analogue exhibited selectively and specifically higher affinity for αvβ3-integrin than other analogues in U87MG cells in comparison with HeLa cells. The subcutaneous U87MG tumor xenograft mice models clearly visualized the uptake of F-HMC-1 in tumor tissue in contrast with normal tissues with tumor-to-normal tissue ratio (T/NT = 15.9 ± 1.1) at 2 h post-injection. These results suggested that F-HMC-1 peptide has potential diagnostic applications for targeting αvβ3-integrin assessed by optical imaging study in U87MG tumor xenograft mice models.
