Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Biomater Adv. 2022 Jun;137:212831. doi: 10.1016/j.bioadv.2022.212831. Epub 2022 May 2.
Adjuvant systemic chemotherapy with gemcitabine (GEM) is recognized as the standard of care to improve the prognosis of patients with resected pancreatic cancer (PC); however, it is greatly limited by poor absorption of chemotherapy agents. Moreover, surgical site infection and Gammaproteobacteria-induced GEM resistance further decrease the chemotherapy efficacy and increase the risk of recurrence and even mortality. Here, we develop an implantable anti-bacterial and anti-cancer fibrous membrane (AAFM) to inhibit PC recurrence in a well-coordinated manner. Our AAFM can be readily prepared via simple co-electrospinning of GEM and poly-L-lactic acid (PLLA) and subsequent tannic acid (TA)-mediated in-situ generation of silver nanoparticles (AgNPs). The resultant membrane presents highly porous fibrous morphology and appropriate mechanical performance. Most importantly, we find the surface-deposited TA/AgNP complexes can exert multiple therapeutic effects: (1) they can act as a fence to extend GEM diffusion route, achieving a sustained drug release; (2) they can fight the pathogenic microorganisms in the local microenvironment and prevent infectious complications and alleviate Gammaproteobacteria-induced chemotherapy resistance; (3) they can combat residual cancer cells to synchronously strengthen the effectiveness of GEM-based chemotherapy. Altogether, our AAFM provides a proof-of-concept demonstration of the integrated anti-cancer and anti-bacterial strategy for enhanced therapeutic efficacy and will inspire the design of other high-performance implants for prevention of tumor relapse.
吉西他滨(GEM)辅助全身化疗被认为是改善可切除胰腺癌(PC)患者预后的标准治疗方法;然而,它受到化疗药物吸收不良的极大限制。此外,手术部位感染和γ变形菌诱导的 GEM 耐药性进一步降低了化疗效果,增加了复发甚至死亡的风险。在这里,我们开发了一种可植入的抗菌和抗癌纤维膜(AAFM),以协调一致的方式抑制 PC 的复发。我们的 AAFM 可以通过简单的 GEM 和聚 L-乳酸(PLLA)共电纺以及随后的单宁酸(TA)介导的原位生成银纳米颗粒(AgNP)来制备。所得膜呈现出高度多孔的纤维形态和适当的机械性能。最重要的是,我们发现表面沉积的 TA/AgNP 复合物可以发挥多种治疗作用:(1)它们可以作为围栏来延长 GEM 的扩散途径,实现持续的药物释放;(2)它们可以对抗局部微环境中的致病微生物,防止感染性并发症,并减轻γ变形菌诱导的化疗耐药性;(3)它们可以对抗残留的癌细胞,同步增强基于 GEM 的化疗效果。总之,我们的 AAFM 为增强治疗效果的综合抗癌和抗菌策略提供了概念验证示范,并将激发其他用于预防肿瘤复发的高性能植入物的设计。