National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
J Mater Chem B. 2020 Feb 26;8(8):1728-1738. doi: 10.1039/c9tb02840d.
Polymer microspheres are attracting wide attention in localized cancer therapy owing to the excellent biocompatibility and drug loading capacity, controllable biodegradation speeds, and minimized systemic toxicity. Herein, we presented poly(ester-thioether) microspheres, porous and nonporous, as drug depots for localized therapy of non-small cell lung cancer (NSCLC). Specifically, erlotinib and α-tocopheryl succinate (α-TOS), which are respectively an epidermal growth factor receptor (EGFR) inhibitor and mitochondria destabilizer, were efficiently loaded into porous and nonporous poly(ester-thioether) microspheres for the treatment of EGFR-overexpressing NSCLC (A549 cells). The poly(ester-thioether) microspheres significantly improved the bioavailability of both erlotinib and α-TOS in comparison to the free drug combination, realizing synergistic inhibition of A549 cells both in vitro and in vivo. The porous microspheres displayed faster degradation and drug release than the nonporous counterpart, thereby showing better anticancer efficacy. Overall, our study reported a new anticancer strategy of erlotinib and α-TOS combination for therapy of NSCLC, and established that poly(ester-thioether) microspheres could be a robust and biodegradable reservoir for drug delivery and localized cancer therapy.
聚合物微球由于具有优异的生物相容性和载药能力、可控的生物降解速度以及最小化的全身毒性，在局部癌症治疗中引起了广泛关注。本文中，我们提出了多孔和无孔的聚（酯-硫醚）微球作为药物库，用于非小细胞肺癌（NSCLC）的局部治疗。具体来说，将表皮生长因子受体（EGFR）抑制剂厄洛替尼和线粒体解偶联剂α-生育酚琥珀酸酯（α-TOS）分别有效地负载到多孔和无孔聚（酯-硫醚）微球中，用于治疗 EGFR 过表达的 NSCLC（A549 细胞）。与游离药物组合相比，聚（酯-硫醚）微球显著提高了厄洛替尼和 α-TOS 的生物利用度，实现了体外和体内对 A549 细胞的协同抑制。多孔微球的降解和药物释放速度比无孔微球快，因此表现出更好的抗癌效果。总的来说，我们的研究报告了一种新的厄洛替尼和 α-TOS 联合治疗 NSCLC 的抗癌策略，并证实聚（酯-硫醚）微球可以作为一种强大的可生物降解的药物输送和局部癌症治疗的储库。
