The residence time of some small molecular imaging and therapeutic agents in tumor tissue is short and the molecules can be easily dispersed, which decreases treatment efficacy. Therefore, methods that enhance oncotherapy performance are of significant importance. Here, we report an in situ self-assembly strategy aimed at enhancing the photothermal therapy of glioblastomas. The probe, ICG-PEP-c(RGD)fk, consisted of a glutathione-reactive self-assembling polypeptide as the skeleton, indocyanine green (ICG) as a theranostic agent, and cyclic Arg-Gly-Asp [c(RGD)fk] peptides as the targeting group. ICG-PEP-c(RGD)fk was synthesized and found to be assembled in the glutathione environment at 9.446 μM in vitro. Human glioblastoma cell line U87MG-luc with high integrin αvβ3 expression was applied to invivo experiments. ICG-PEP-c(RGD)fk provided clearer tumor imaging and had a tumor retention time of 6.12 times longer than that of ICG-c(RGD)fk. In therapeutic experiments, ICG-PEP-c(RGD)fk significantly suppressed glioblastoma growth and the tumor volume was 2.61 times smaller than in the ICG-c(RGD)fk group at the end of the observation period. Moreover, the median survival time of ICG-PEP-c(RGD)fk group was significantly improved by 2.78 times compared with that of the control group. In conclusion, glutathione-reactive self-assembling peptides are capable of increasing the tumor retention time and improving the photothermal therapeutic effect. The in situ self-assembly strategy is a potential and feasible method to enhance oncotherapy.
Keywords: glioblastoma; in situ self-assembly; peptide; photothermal therapy; theranostics.