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Self-Healing pH- and Enzyme Stimuli-Responsive Hydrogels for Targeted Delivery of Gemcitabine To Treat Pancreatic Cancer
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-08-10 00:00:00 , DOI: 10.1021/acs.biomac.8b00959 Panayiotis Bilalis 1 , Dimitrios Skoulas 1 , Anastasios Karatzas 1 , John Marakis 2, 3 , Athanasios Stamogiannos 4 , Chrisida Tsimblouli 5 , Evangelia Sereti 5 , Efstratios Stratikos 4 , Konstantinos Dimas 5 , Dimitris Vlassopoulos 2, 3 , Hermis Iatrou 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-08-10 00:00:00 , DOI: 10.1021/acs.biomac.8b00959 Panayiotis Bilalis 1 , Dimitrios Skoulas 1 , Anastasios Karatzas 1 , John Marakis 2, 3 , Athanasios Stamogiannos 4 , Chrisida Tsimblouli 5 , Evangelia Sereti 5 , Efstratios Stratikos 4 , Konstantinos Dimas 5 , Dimitris Vlassopoulos 2, 3 , Hermis Iatrou 1
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A novel, multifunctional hydrogel that exhibits a unique set of properties for the effective treatment of pancreatic cancer (PC) is presented. The material is composed of a pentablock terpolypeptide of the type PLys-b-(PHIS-co-PBLG)-PLys-b-(PHIS-co-PBLG)-b-PLys, which is a noncytotoxic polypeptide. It can be implanted via the least invasive route and selectively delivers gemcitabine to efficiently treat PC. Simply mixing the novel terpolypeptide with an aqueous solution of gemcitabine within a syringe results in the facile formation of a hydrogel that has the ability to become liquid under the shear rate of the plunger. Upon injection in the vicinity of cancer tissue, it immediately reforms into a hydrogel due to the unique combination of its macromolecular architecture and secondary structure. Because of its pH responsiveness, the hydrogel only melts close to PC; thus, the drug can be delivered directionally toward the cancerous rather than healthy tissues in a targeted, controlled, and sustained manner. The efficacy of the hydrogel was tested in vivo on human to mouse xenografts using the drug gemcitabine. It was found that the efficacy of the hydrogel loaded with only 40% of the drug delivered in one dose was equal to or slightly better than the peritumoral injection of 100% of the free drug delivered in two doses, the typical chemotherapy used in clinics so far. This result suggests that the hydrogel can direct the delivery of the encapsulated drug effectively in the tumor tissue. Enzymes lead to its biodegradation, avoiding removal by resection of the polypeptidic carrier after cargo delivery. The unique properties of the hydrogel formed can be predetermined through its molecular characteristics, rendering it a promising modular material for many biological applications.
中文翻译：
自愈的pH和酶促响应水凝胶用于吉西他滨靶向治疗胰腺癌的靶向递送。
提出了一种新颖的多功能水凝胶，该水凝胶显示出一套有效治疗胰腺癌（PC）的独特性能。该材料是由类型PLys-的五嵌段terpolypeptide的b - （PHIS-共-PBLG）-PLys- b - （PHIS-共-PBLG） - b-PLys，它是一种无细胞毒性的多肽。它可以通过侵入性最小的途径植入，并选择性地递送吉西他滨以有效治疗PC。在注射器内简单地将新的三肽与吉西他滨的水溶液混合，即可轻松形成水凝胶，该水凝胶具有在柱塞的剪切速率下变成液体的能力。在癌组织附近注射后，由于其大分子结构和二级结构的独特结合，它立即重新形成水凝胶。由于其对pH的响应能力，水凝胶只会在接近PC的位置融化。因此，可以靶向，控制和持续的方式将药物定向输送到癌性组织，而不是健康组织。水凝胶的功效在体内进行了测试使用吉西他滨的药物对人到小鼠的异种移植物进行治疗。已发现仅以一剂剂量递送的40％药物加载的水凝胶的疗效等于或略高于肿瘤周围注射以两种剂量递送的100％的游离药物的剂量，这是临床上常用的化学疗法，因此远的。该结果表明水凝胶可以指导封装的药物在肿瘤组织中的有效递送。酶导致其生物降解，避免在货物交付后通过切除多肽载体将其去除。形成的水凝胶的独特性质可以通过其分子特性预先确定，使其成为许多生物学应用中有希望的模块化材料。
更新日期：2018-08-10
中文翻译：
自愈的pH和酶促响应水凝胶用于吉西他滨靶向治疗胰腺癌的靶向递送。
提出了一种新颖的多功能水凝胶，该水凝胶显示出一套有效治疗胰腺癌（PC）的独特性能。该材料是由类型PLys-的五嵌段terpolypeptide的b - （PHIS-共-PBLG）-PLys- b - （PHIS-共-PBLG） - b-PLys，它是一种无细胞毒性的多肽。它可以通过侵入性最小的途径植入，并选择性地递送吉西他滨以有效治疗PC。在注射器内简单地将新的三肽与吉西他滨的水溶液混合，即可轻松形成水凝胶，该水凝胶具有在柱塞的剪切速率下变成液体的能力。在癌组织附近注射后，由于其大分子结构和二级结构的独特结合，它立即重新形成水凝胶。由于其对pH的响应能力，水凝胶只会在接近PC的位置融化。因此，可以靶向，控制和持续的方式将药物定向输送到癌性组织，而不是健康组织。水凝胶的功效在体内进行了测试使用吉西他滨的药物对人到小鼠的异种移植物进行治疗。已发现仅以一剂剂量递送的40％药物加载的水凝胶的疗效等于或略高于肿瘤周围注射以两种剂量递送的100％的游离药物的剂量，这是临床上常用的化学疗法，因此远的。该结果表明水凝胶可以指导封装的药物在肿瘤组织中的有效递送。酶导致其生物降解，避免在货物交付后通过切除多肽载体将其去除。形成的水凝胶的独特性质可以通过其分子特性预先确定，使其成为许多生物学应用中有希望的模块化材料。
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