Boosting of the enhanced permeability and retention effect with nanocapsules improves the therapeutic effects of cetuximab

Chao Yang, Yanli Tan, Hongzhao Qi, et al.

Abstract


Objective: The introduction of therapeutic antibodies (tAbs) into clinical practice has revolutionized tumor treatment strategies, buttheir tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs.

Methods: We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention(EPR) effect. This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by theimmune system. The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo.

Results: The accumulation of Nano(cetuximab) within subcutaneous PC9 tumors was gradually enhanced over 6 days after single doseadministration, which was contrary to the biodistribution of native cetuximab. Nano(cetuximab) accumulated in tumor tissues via the EPReffect and released cetuximab. The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induceself-augmentation of the EPR effect, which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab).Compared with single dose administration of native cetuximab, Nano(cetuximab) showed an effective tumor suppressive effect for 3 weeks.

Conclusions: The nanocapsule-based delivery system efficiently delivered tAbs to tumor tissues and released them to boost theEPR effect, which facilitated further tumor accumulation of the tAbs. This novel self-augmentation of the EPR effect facilitated bythe biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs, andstimulated new ideas for antibody-based tumor therapy.

Cite this article as: Yang C, Tan Y, Qi H, Zhou J, Long L, Zhan Q, et al. Boostingof the enhanced permeability and retention effect with nanocapsules improvesthe therapeutic effects of cetuximab. Cancer Biol Med. 2020; 17: 433-443.doi: 10.20892/j.issn.2095-3941.2019.0292


Keywords


Endothelial cells; EPR effect; nanocapsule; single dose administration; therapeutic antibody

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