Dual Receptor Targeting Cell Penetrating Peptide Modified Liposome for Glioma and Breast Cancer Postoperative Recurrence Therapy

Abstract

Cell penetrating peptides (CPPs) were widely used as motifs for drug delivery to tumor. In former study, an RGD reverse sequence dGR was used to develop active-targeting liposome R8dGR-Lip, which showed well penetrating ability and treatment efficiency on glioma model. However, recurrence after tumor resection caused by post-operative residual cancer cells was a huge obstacle in tumor treatment. In consideration of the effective anti-cancer effect of PTX-R8dGR-Lip when treating glioma in former study, we decide to evaluate its pharmacodynamics on tumor resection models, which were more invasive and resistant. In vitro, the effectiveness of PTX-R8dGR-Lip in reducing tumor initiating cell (TIC) was investigated using mammosphere formation. In vivo, the inhibition efficiency of PTX-R8dGR-Lip on C6 glioma recurrence and 4T1 breast cancer recurrence model were evaluated, including tumor bioluminescence imaging, survival rate and immumohistochemical staining, etc.. C6 mammosphere formation rate of PTX-R8dGR-Lip group was 48.06 ± 2.72%, and 4T1 mammosphere formation rate of PTX-R8dGR-Lip group was 39.51 ± 4.02% when PBS group was set as 100%. C6 and 4T1 bioluminescent tumor resected model were established, then effectiveness of different PTX-loaded preparations were evaluated on these two models. PTX-R8dGR-Lip could obviously inhibit tumor recurrence, prolong survival rate and reduce tumor tissue invasion. PTX-R8dGR-Lip could reduce post-operative recurrence rate, prolong survival time, and decrease the proliferation of residual cancer cells through regulating the expression of recurrence-related cytokines.