Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, PR China.
Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, PR China.
Colloids Surf B Biointerfaces. 2020 Jul;191:111000. doi: 10.1016/j.colsurfb.2020.111000. Epub 2020 Mar 28.
To promote the targeted cancer therapy, the pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate was successfully constructed. Herein, water-soluble vitamin B6 with pKa (5.6) was chemically conjugated to lipid-soluble vitamin E succinate (α-TOS), which showed selective cancer cell killing ability and this amphiphilic small molecule vitamin conjugate could self-assemble to be free nanoparticles (NPs) and doxorubicin-loaded NPs (α-TOS-B6-NPs-DOX). The small molecule nanodrugs could perform the following characteristic: (i) stability in the sodium dodecyl sulfonate (SDS) solution and long-term storage stability in PBS via surface negative charge; (ii) tumor accumulation by enhanced penetration and retention (EPR) effect; (iii) improved cellular internalization by means of vitamin B6 transporting membrane carrier (VTC); and (iv) facilitating endosomal escape and rapid drug release for synergistic toxicity to tumor cells via charge reversal and ester hydrolysis at intracellular pH and/or esterase. Moreover, α-TOS-B6-NPs-DOX exhibited long blood circulation stability and significant tumor accumulation and inhibition with the decreased side effects in vivo. Thus, the pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate could be the potential drug carriers in targeted synergistic cancer therapy.
为了促进靶向癌症治疗，成功构建了由两亲性维生素 B6-E 类似物缀合物自组装而成的 pH 敏感小分子纳米药物。在此，水溶性维生素 B6（pKa=5.6）被化学偶联到脂溶性维生素 E 琥珀酸酯（α-TOS）上，表现出选择性的癌细胞杀伤能力，这种两亲性小分子维生素缀合物可以自组装成游离纳米颗粒（NPs）和阿霉素负载纳米颗粒（α-TOS-B6-NPs-DOX）。小分子纳米药物具有以下特点：（i）在十二烷基硫酸钠（SDS）溶液中稳定，在 PBS 中通过表面负电荷具有长期储存稳定性；（ii）通过增强渗透和保留（EPR）效应实现肿瘤积累；（iii）通过维生素 B6 转运膜载体（VTC）提高细胞内化能力；（iv）通过电荷反转和细胞内 pH 和/或酯酶的酯水解促进内涵体逃逸和快速药物释放，从而对肿瘤细胞产生协同毒性。此外，α-TOS-B6-NPs-DOX 表现出长的血液循环稳定性和显著的肿瘤积累和抑制作用，同时体内副作用降低。因此，由两亲性维生素 B6-E 类似物缀合物自组装而成的 pH 敏感小分子纳米药物可以作为靶向协同癌症治疗的潜在药物载体。
