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

Abstract

PURPOSE:

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.

METHOD:

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 4 T1 breast cancer recurrence model were evaluated, including tumor bioluminescence imaging, survival rate and immumohistochemical staining, etc..

RESULTS:

C6 mammosphere formation rate of PTX-R8dGR-Lip group was 48.06 ± 2.72%, and 4 T1 mammosphere formation rate of PTX-R8dGR-Lip group was 39.51 ± 4.02% when PBS group was set as 100%. C6 and 4 T1 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.

CONCLUSION:

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.

• Authors: Yue Qiu, Qianwen Yu, Yayuan Liu, Jiajing Tang, Xuhui Wang, Zhengze Lu, Zhuping Xu, Qin He
• Journal: Pharmaceutical research (Pharm Res) Vol. 35 Issue 7 Pg. 130 (Apr 26 2018) ISSN: 1573-904X [Electronic] United States
• PMID: 29700620 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Liposomes
• Oligopeptides
• Peptide Fragments
• Polyethylene Glycols
• arginyl-glycyl-aspartic acid

Topics

• Animals
• Antineoplastic Agents (administration & dosage, metabolism)
• Brain Neoplasms (drug therapy, metabolism, surgery)
• Breast Neoplasms (drug therapy, metabolism, surgery)
• Cell Line, Tumor
• Drug Delivery Systems (methods)
• Female
• Glioma (drug therapy, metabolism, surgery)
• Humans
• Liposomes
• Mice
• Mice, Inbred BALB C
• Neoplasm Recurrence, Local (drug therapy, metabolism)
• Oligopeptides (administration & dosage, metabolism)
• Peptide Fragments (administration & dosage, metabolism)
• Polyethylene Glycols (administration & dosage, metabolism)
• Postoperative Care (methods)
• Rats
• Xenograft Model Antitumor Assays (methods)