Tissue Regeneration and Molecular Cell Engineering Lab, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA.
Ann Biomed Eng. 2011 Sep;39(9):2374-87. doi: 10.1007/s10439-011-0335-0. Epub 2011 Jun 25.
A multifaceted strategy using a composite of anti-cancer nanotherapeutic and natural biomaterials silk fibroin (SF) and chitosan (CS) blend scaffolds was investigated for the treatment of a tissue defect post-tumor resection by providing local release of the therapeutic and filling of the defect site with the regenerative bioscaffolds. The scaffold-emodin nanoparticle composites were fabricated and characterized for drug entrapment and release, mechanical strength, and efficacy against GILM2 breast cancer cells in vitro and in vivo in a rat tumor model. Emodin nanoparticles were embedded in SF and SFCS scaffolds and the amount of emodin entrapment was a function of the scaffold composition and emodin loading concentration. In vitro, there was a burst release of emodin from all scaffolds during the first 2 days though it was detected even after 24 days. Increase in emodin concentration in the scaffolds decreased the overall elastic modulus and ultimate tensile strength of the scaffolds. After 6 weeks of in vivo implantation, the cell density (p < 0.05) and percent degradation (p < 0.01) within the remodeled no emodin SFCS scaffold was significantly higher than the emodin loaded SFCS scaffolds, although there was no significant difference in the amount of collagen deposition in the regenerated SFCS scaffold. The presence and release of emodin from the SFCS scaffolds inhibited the integration of SFCS into the adjacent tumor due to the formation of an interfacial barrier of connective tissue that was lacking in emodin-free SFCS scaffolds. While no significant difference in tumor size was observed between the in vivo tested groups, tumors treated with emodin loaded SFCS scaffolds had decreased presence and size and similar regeneration of new tissue as compared to no emodin SFCS scaffolds.
一种使用抗癌纳米治疗剂和天然生物材料丝素纤维（SF）和壳聚糖（CS）混合支架的多方面策略，通过局部释放治疗剂和用再生生物支架填充缺陷部位，用于治疗肿瘤切除后的组织缺陷。制备并表征了支架-大黄素纳米粒子复合材料，用于药物包封和释放、机械强度以及在体外和体内大鼠肿瘤模型中对 GILM2 乳腺癌细胞的疗效。大黄素纳米粒子嵌入 SF 和 SFCS 支架中，大黄素的包封量是支架组成和大黄素负载浓度的函数。在体外，所有支架在前 2 天都会出现大黄素的爆发释放，但即使在 24 天后也能检测到。支架中大黄素浓度的增加降低了支架的整体弹性模量和极限拉伸强度。在体内植入 6 周后，无大黄素 SFCS 支架内的细胞密度（p<0.05）和降解百分比（p<0.01）显著高于大黄素负载 SFCS 支架，尽管在再生 SFCS 支架中胶原沉积量没有显著差异。由于缺乏大黄素的 SFCS 支架中结缔组织界面屏障的形成，SFCS 支架中大黄素的存在和释放抑制了 SFCS 与相邻肿瘤的整合。虽然体内测试组之间的肿瘤大小没有显著差异，但与无大黄素 SFCS 支架相比，用大黄素负载 SFCS 支架治疗的肿瘤其存在和大小减少，新组织的再生相似。
