基于生物可降解、治疗性和自报告发光多孔硅微球的协同促进血管生成的共递药平台。
A co-delivery platform for synergistic promotion of angiogenesis based on biodegradable, therapeutic and self-reporting luminescent porous silicon microparticles.
机构信息
Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China.
Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China; Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
出版信息
Biomaterials. 2021 May;272:120772. doi: 10.1016/j.biomaterials.2021.120772. Epub 2021 Mar 26.
Insufficient angiogenesis happened in body defects such as ulceration, coronary heart disease, and chronic wounds constitutes a major challenge in tissue regeneration engineering. Owing to the poor bioactivity and maintenance of pro-angiogenic cells and factors during transplantation, new bioactive materials to tackle the barrier are highly desirable. Herein, we demonstrate a co-delivery platform for synergistic promotion of angiogenesis based on biodegradable, therapeutic, and self-reporting luminescent porous silicon (PSi) microparticles. The biodegradable and biocompatible PSi microparticles could quickly release therapeutic Si ions, which is bioactive to promote cell migration, tube formation, and angiogenic gene expression in vitro. To construct a highly efficient angiogenesis treatment platform, vascular endothelial growth factor (VEGF) was electrostatically adsorbed by PSi microparticles for effective drug loading and delivery. The dual therapeutic components (Si ions and VEGF) could release with the dissolution of Si skeleton, accompanying by the decay of photoluminescence (PL) intensity and blue shift of the maximum PL wavelength. Therefore, real-time drug release could be self-reported and assessed with the two-dimensional PL signal. The co-delivery of Si ions and VEGF displayed synergistic effect and highly efficient angiogenesis, which was evidenced by the enhancement of endothelial cell migration and tube formation in vitro with approximately 1.5-5 times higher than control. The blood vessel formation in vivo was also significantly improved as shown by the chick chorioallantoic membrane (CAM) model, in which the total length, size and junctions exhibited 2.1 ± 0.4, 4 ± 0.4, and 3.9 ± 0.3 times in comparison to control, respectively. The PSi and VEGF co-delivery system display great potential in tissue engineering as a biodegradable and self-reporting theranostic platform to promote angiogenesis.
体内缺陷如溃疡、冠心病和慢性创面等部位的血管生成不足是组织再生工程面临的主要挑战。由于在移植过程中促血管生成细胞和因子的生物活性和维持效果不佳，因此非常需要新的生物活性材料来解决这一难题。在此，我们展示了一种基于可生物降解的、治疗性的、具有自报告发光性能的多孔硅（PSi）微球的协同促进血管生成的联合递药平台。可生物降解和生物相容的 PSi 微球能够快速释放具有生物活性的治疗性 Si 离子，促进细胞迁移、管形成和体外血管生成基因表达。为构建高效的血管生成治疗平台，通过静电吸附将血管内皮生长因子（VEGF）加载到 PSi 微球上，实现有效的药物负载和递送。两种治疗性成分（Si 离子和 VEGF）可随着 Si 骨架的溶解而释放，伴随着光致发光（PL）强度的衰减和最大 PL 波长的蓝移。因此，可通过二维 PL 信号对实时药物释放进行自我报告和评估。Si 离子和 VEGF 的联合递送具有协同作用，可高效促进血管生成，这表现在体外增强了内皮细胞的迁移和管形成，其效率约为对照组的 1.5-5 倍。体内血管生成也得到了显著改善，鸡胚绒毛尿囊膜（CAM）模型显示，总长度、大小和连接数分别比对照组增加了 2.1±0.4、4±0.4 和 3.9±0.3 倍。PSi 和 VEGF 的联合递送系统作为一种可生物降解的、自报告的治疗学平台，具有促进血管生成的巨大潜力，可用于组织工程。
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