Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do 14662, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Republic of Korea.
Biomacromolecules. 2021 Feb 8;22(2):723-731. doi: 10.1021/acs.biomac.0c01514. Epub 2020 Dec 6.
In this study, the strategy of transient generation of holes in the liposome surface has been shown to enable safe encapsulation of a high-molecular weight antibody (rituximab, ∼140 kDa) within liposomes. These transient holes generated using our magnetoporation method allowed rituximab to safely enter the liposomes, and then the holes were plugged using hyaluronic acid grafted with 3-diethylaminopropylamine (DEAP). In the tumor microenvironment, the resulting liposomal rituximab was destabilized because of the ionization of the DEAP moiety at the acidic pH 6.5, resulting in extensive release of rituximab. Consequently, the rituximab released from the liposomes accumulated at high levels in tumors and bound to the CD20 receptors overexpressed on Burkitt Ramos cells. This event led to significant enhancement in tumor cell ablation through rituximab-mediated complement-dependent cytotoxicity and Bcl-2 signaling inhibition-induced cell apoptosis.
在这项研究中，我们展示了一种在脂质体表面瞬时生成孔的策略，该策略可实现将高分子量抗体（利妥昔单抗，约 140 kDa）安全地封装在脂质体内部。我们使用磁转染法生成的这些瞬时孔允许利妥昔单抗安全进入脂质体，然后使用接枝有 3-二乙氨基丙基胺（DEAP）的透明质酸将孔堵塞。在肿瘤微环境中，由于 DEAP 部分在酸性 pH 值 6.5 下发生离子化，导致脂质体利妥昔单抗不稳定，从而导致利妥昔单抗大量释放。因此，从脂质体中释放的利妥昔单抗在肿瘤中大量积累，并与 Burkitt Ramos 细胞上过度表达的 CD20 受体结合。这一事件通过利妥昔单抗介导的补体依赖性细胞毒性和 Bcl-2 信号抑制诱导的细胞凋亡，显著增强了肿瘤细胞的消融。
