Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
Cancer Biol Med. 2020 May 15;17(2):433-443. doi: 10.20892/j.issn.2095-3941.2019.0292.
The introduction of therapeutic antibodies (tAbs) into clinical practice has revolutionized tumor treatment strategies, but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs. : 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 the immune system. The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs . : The accumulation of Nano(cetuximab) within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration, which was contrary to the biodistribution of native cetuximab. Nano(cetuximab) accumulated in tumor tissues the EPR effect and released cetuximab. The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-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. : The nanocapsule-based delivery system efficiently delivered tAbs to tumor tissues and released them to boost the EPR effect, which facilitated further tumor accumulation of the tAbs. This novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs, and stimulated new ideas for antibody-based tumor therapy.
治疗性抗体（tAbs）引入临床实践彻底改变了肿瘤治疗策略，但由于 tAbs 的快速降解和有限的肿瘤积累，其肿瘤治疗效率仍远低于预期。我们开发了一种基于纳米胶囊的递药系统，以诱导增强型渗透滞留（EPR）效应的自我增强。该系统在不断穿透血肿瘤屏障进入肿瘤的同时，还能避免 tAbs 被免疫系统攻击。通过单次给予纳米胶囊-tAbs 进行了生物分布和治疗效果测试。在单次给予后 6 天内，纳米（西妥昔单抗）在皮下 PC9 肿瘤中的积累逐渐增强，这与天然西妥昔单抗的生物分布相反。纳米（西妥昔单抗）在肿瘤组织中积累，增强了 EPR 效应并释放了西妥昔单抗。释放的西妥昔单抗作用于血管内皮细胞，破坏血肿瘤屏障并诱导 EPR 效应的自我增强，这反过来又有助于长循环纳米（西妥昔单抗）进一步在肿瘤中的积累。与单次给予天然西妥昔单抗相比，纳米（西妥昔单抗）在 3 周内表现出有效的肿瘤抑制作用。基于纳米胶囊的递药系统能够有效地将 tAbs 递送到肿瘤组织中，并将其释放以增强 EPR 效应，从而促进 tAbs 在肿瘤中的进一步积累。这种由 tAbs 和纳米技术的生物学特性促进的 EPR 效应的自我增强有助于提高 tAbs 的治疗效果，并为抗体为基础的肿瘤治疗激发了新的思路。
