Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill/North Carolina State University, Chapel Hill, NC 27599, USA.
Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Control Release. 2022 Apr;344:147-156. doi: 10.1016/j.jconrel.2022.02.024. Epub 2022 Feb 22.
Surgery is an important treatment for cancer; however, local recurrence following macroscopically-complete resection is common and a significant cause of morbidity and mortality. Systemic chemotherapy is often employed as an adjuvant therapy to prevent recurrence of residual disease, but has limited efficacy due to poor penetration and dose-limiting off-target toxicities. Selective delivery of chemotherapeutics to the surgical bed may eliminate residual tumor cells while avoiding systemic toxicity. While this is challenging for traditional drug delivery technologies, we utilized advances in 3D printing and drug delivery science to engineer a drug-loaded arrowhead array device (AAD) to overcome these challenges. We demonstrated that such a device can be designed, fabricated, and implanted intraoperatively and provide extended release of chemotherapeutics directly to the resection area. Using paclitaxel and cisplatin as model drugs and murine models of cancer, we showed AADs significantly decreased local recurrence post-surgery and improved survival. We further demonstrated the potential for fabricating personalized AADs for intraoperative application in the clinical setting.
手术是癌症的重要治疗手段；然而，肉眼下完全切除后的局部复发很常见，是发病率和死亡率的重要原因。系统化疗常作为辅助治疗手段，以预防残留疾病的复发，但由于渗透不良和剂量限制的脱靶毒性，疗效有限。将化疗药物选择性递送到手术部位可能在避免全身毒性的同时消除残留肿瘤细胞。虽然这对传统药物输送技术来说具有挑战性，但我们利用 3D 打印和药物输送科学的进步，设计并制造了一种载药箭头阵列装置（AAD），以克服这些挑战。我们证明，这样的装置可以设计、制造并在手术过程中植入，并直接向切除区域提供化疗药物的延长释放。我们使用紫杉醇和顺铂作为模型药物和癌症的小鼠模型，表明 AAD 显著降低了手术后的局部复发率并提高了生存率。我们进一步证明了制造用于临床手术中应用的个性化 AAD 的潜力。
