Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Gyeonggi-do 14662, Republic of Korea.
Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Gyeonggi-do 14662, Republic of Korea; Department of Biomedical Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Gyeonggi-do 14662, Republic of Korea.
Carbohydr Polym. 2020 Feb 15;230:115563. doi: 10.1016/j.carbpol.2019.115563. Epub 2019 Nov 6.
We report here the tumor-implantable microparticles with a honeycomb-like porous structure. These microparticles were prepared by electrospinning using γ-cyclodextrin (γ-CD) conjugated with 3-(diethylamino)propylamine (DEAP, as a pH-responsive moiety), named γ-CD-DEAP. The resulting microparticles had pore channels (constructed using γ-CD-DEAP) extending into the deep compartment of the microparticles and allowing efficient paclitaxel (PTX, as a chemotherapeutic model drug) entrapment by a simple hole-filling encapsulation process. Importantly, the hydrophobic DEAP (at pH 7.4) in the γ-CD-DEAP microparticles changed to hydrophilic DEAP (at pH 6.8) because of its acidic pH-induced protonation. This phenomenon resulted in an acidic pH-activated particle destruction by a charge-charge repulsion between the protonated DEAP moieties and allowed a pH-triggered release of the encapsulated PTX from the collapsed microparticles. Consequently, γ-CD-DEAP microparticles implanted at the tumor site caused a significant enhancement of the in vitro/in vivo tumor cell ablation, suggesting their significant potential as a chemotherapeutic implant for tumor therapy.
我们在此报告了具有蜂窝状多孔结构的肿瘤植入式微粒。这些微粒是通过静电纺丝用 γ-环糊精（γ-CD）与 3-（二乙氨基）丙胺（DEAP，作为 pH 响应部分）偶联制备的，命名为 γ-CD-DEAP。所得微粒具有孔道（使用 γ-CD-DEAP 构建）延伸到微粒的深部，允许通过简单的孔填充包封过程有效包埋紫杉醇（PTX，作为化学治疗模型药物）。重要的是，由于酸性 pH 诱导的质子化，γ-CD-DEAP 微粒中的疏水性 DEAP（在 pH 7.4 时）变成亲水性 DEAP（在 pH 6.8 时）。这种现象导致由于质子化的 DEAP 部分之间的电荷-电荷排斥而使酸性 pH 激活的颗粒破坏，并允许从塌陷的微粒中 pH 触发释放包封的 PTX。因此，在肿瘤部位植入的 γ-CD-DEAP 微粒导致体外/体内肿瘤细胞消融的显著增强，表明它们作为肿瘤治疗的化学治疗植入物具有重要的潜力。
