Synergistic effect of a drug loaded electrospun patch and systemic chemotherapy in pancreatic cancer xenograft.
Synergistic effect of a drug loaded electrospun patch and systemic chemotherapy in pancreatic cancer xenograft.
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DOI：
10.1038/s41598-017-12670-3
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发表时间：
2017-09-28
影响因子：
4.6
通讯作者：
Shim IK
中科院分区：
文献类型：
--
作者：
Jun E;Kim SC;Lee CM;Oh J;Lee S;Shim IK
胰腺癌根治性切除术后即使辅助化疗，局部复发率高，预后差。本研究的目的是探讨局部给药联合小剂量全身化疗是否能提高化疗的疗效，同时降低全身毒性。采用静电纺丝技术制备了聚L-乳酸基5-FU缓释贴片，并首次在体外证实了其对肿瘤的杀伤作用。在皮下和原位小鼠模型中，5-FU贴剂直接粘附于肿瘤，并诱导肿瘤大小显著减小。通过皮下模型中的肿瘤大小测量、非侵入性生物成像和组织学比较全身吉西他滨治疗组、5-FU药物释放贴剂组和全身吉西他滨+5-FU贴剂组。局部药物贴剂和全身化疗的组合导致持续时间更长的肿瘤抑制作用增加，以及生存率增加。组织学显示联合组细胞凋亡程度较高。所有小鼠的全身毒性在给药后7天内恢复。结论：使用生物相容性聚合物贴片局部给药可显著抑制肿瘤生长，与全身化疗联合使用比单一全身化疗更有效。
Pancreatic cancer has a high rate of local recurrence and poor prognosis even with adjuvant chemotherapy after curative resection. The aim of this study was to investigate if local drug delivery combined with low dose systemic chemotherapy can increase the therapeutic effect of chemotherapy while reducing systemic toxicities. Poly-L-lactic acid-based 5-FU releasing patch was fabricated by electrospinning, and its tumour killing effects were first confirmed in vitro. The 5-FU patch directly adhered to the tumour in subcutaneous and orthotopic murine models, and induced a significant decrease in tumour size. Systemic gemcitabine treatment group, 5-FU drug releasing patch group, and systemic gemcitabine plus 5-FU patch group were compared by tumour size measurement, non-invasive bio-imaging, and histology in subcutaneous models. Combination of local drug patch and systemic chemotherapy led to increased tumour suppression effects that lasted longer, as well as increased survival rate. Histology revealed higher degree of apoptosis in the combined group. Systemic toxicity was recovered within 7 days after the treatment in all mice. Conclusively, local drug delivery using biocompatible polymer patch significantly inhibited tumour growth, and combination with systemic chemotherapy was more effective than single systemic chemotherapy.
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影响因子：
5.5
作者：
Li X;Zhang XN;Li XD;Chang J
通讯作者：
Chang J
影响因子：
9.5
作者：
Han, Daewoo;Steckl, Andrew J.
通讯作者：
Steckl, Andrew J.
针对胰腺癌肿瘤相互作用的新型治疗策略。
影响因子：
4
作者：
Hamada S;Masamune A;Shimosegawa T
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41.2
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Artzi N
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3.5
作者：
Chadha, Awalpreet S.;Khoo, Allison;Krishnan, Sunil
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Krishnan, Sunil