Schiff based injectable hydrogel for in situ pH-triggered delivery of doxorubicin for breast tumor treatment
Schiff based injectable hydrogel for in situ pH-triggered delivery of doxorubicin for breast tumor treatment
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基于希夫的可注射水凝胶，用于原位 pH 触发输送阿霉素，用于乳腺肿瘤治疗
DOI：
10.1039/c4py00631c
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发表时间：
2014
影响因子：
4.6
通讯作者：
Xing Malcolm M. Q.
中科院分区：
文献类型：
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作者：
Shi Junbin;Guobao Wang;Chen Hongli;Zhong Wen;Qiu Xiaozhong;Xing Malcolm M. Q.
在这项研究中，我们报告了一种简便的方法来开发可注射水凝胶与原位和pH敏感的药物输送系统用于癌症治疗。该水凝胶是基于改性壳聚糖和海藻酸钠。我们通过在DOX中的酮基和S-chi中的胺基之间的席夫碱将多柔比星（DOX）缀合到琥珀酸化壳聚糖（S-chi），这导致DOX在酸性肿瘤微环境刺激下的pH敏感性释放。水凝胶在几分钟内形成，同时DOX缀合的S-chi与氧化的藻酸盐混合。通过低温成像、FTIR和流变学测试表征水凝胶结构。测试响应于不同pH值的DOX释放曲线。MTT试验表明该水凝胶的毒性较低。当负载DOX时，凝胶反过来有效地抑制肿瘤细胞MCF-7的生长。最后，将载有DOX的水凝胶注射到异种移植乳腺肿瘤模型中并显著抑制肿瘤生长。
In this study, we report a facile approach to develop an injectable hydrogel with an in situ and pH sensitive drug delivery system for cancer treatment. The hydrogel was based on modified chitosan and alginate. We conjugated doxorubicin (DOX) to succinated chitosan (S-chi) via a Schiff base between a ketone group in the DOX and an amine group in the S-chi, which led to a pH sensitive release of DOX upon the stimulus of an acidic tumor microenvironment. Hydrogel formed in minutes while DOX conjugated S-chi was mixed with oxidized alginate. The hydrogel structure was characterized by cryo-imaging, FTIR and a rheology test. The DOX release profiles were tested in response to different pH values. The MTT assay showed a low toxicity of the hydrogel. The gel in turn inhibited the growth of tumor cells MCF-7 effectively when loaded with DOX. Finally, the DOX laden hydrogel was injected into the xenograft breast tumor model and significantly inhibited tumor growth.