Abstract:
The design and development of an efficacious
tumor-specific drug-delivery system is a challenging task. In this
study, we have synthesized target-specific small peptide substrates
on an octaguanidine sorbitol scaffold, named small molecular
targeted drug-delivery conjugate (SMTDDC). The SMTDDC
fabrication, with dual targeting cRGD and Cathepsin B (Cath B)-
specific tripeptide (Glu-Lys-Phe), altered the microtubule network
of glioblastoma cells by the orchestrated release of the cytotoxic
paclitaxel (PTX). Cath B assisted PTX delivery was monitored by
high-performance liquid chromatography and Surface-Enhanced
Raman Scattering (SERS) modalities. The time-dependent SERS
fingerprinting and imaging revealed a fast and accurate PTX release profile and subsequent in vitro cytotoxicity as well as the
apoptotic events and microtubule network alteration in U-87 MG glioblastoma cells. Furthermore, SMTDDC displayed adequate
stability under physiological conditions and demonstrated biocompatibility toward red blood cells and lymphocytes. This study
indicated a new insight on SERS-guided peptidomimetic sorbitol molecular transporter, enabling a greater promise with high
potential for the further development of PTX delivery in glioblastoma treatment.
