Glycated chitosan as a new non-toxic immunological stimulant.

Glycated chitosan as a new non-toxic immunological stimulant.
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DOI:
10.1080/08923970802629593
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发表时间:
2009-06
影响因子:
3.3
通讯作者:
Chen WR
Chen WR
中科院分区:
医学4区
文献类型:
--
作者:
Song S;Zhou F;Nordquist RE;Carubelli R;Liu H;Chen WR

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壳聚糖能够刺激免疫反应。但由于壳聚糖不溶于水,限制了其在生物领域的应用。通过将半乳糖分子连接到壳聚糖分子上,合成了一种新型的水溶性化合物--糖化壳聚糖(GC)。GC被设计用于免疫刺激和光疗相结合的转移性肿瘤的治疗。为探讨GC的可能毒性,将正常细胞和肿瘤细胞分别与不同浓度的GC孵育,测定细胞存活率。对于活体研究,将GC溶液喂入或注射到动物体内,通过观察动物和重要器官的组织学检查来确定其毒性。在培养细胞或动物实验中没有观察到GC的毒性作用。此外,通过体外刺激巨噬细胞分泌肿瘤坏死因子α来研究GC的免疫作用。体内研究表明,激光免疫治疗可以提高转移性乳腺肿瘤大鼠的存活率。我们的体外和体内实验结果表明,GC具有很强的免疫刺激性。GC的无毒性质和免疫活性使其成为治疗转移性肿瘤的潜在免疫佐剂。
Chitosan is capable to stimulate immune responses. However, because chitosan is not water soluble, it has limited biological applications. By attaching galactose molecules to the chitosan molecules, a new water-soluble compound, glycated chitosan (GC), was synthesized. GC was designed for immune stimulations in combination with phototherapies in the treatment of metastatic tumors. To investigate the possible toxicity of GC, cultures of normal and tumor cells were incubated with GC of different concentrations and the cell viabilities were determined. For in vivo studies, GC solution was fed or injected to animals and its toxicity was determined through observations of animals and histological examinations of vital organs. No toxic effects of GC were observed in cultured cells or in animal studies. In addition, the immunological effect of GC was investigated through its stimulation of TNFα secretion by macrophages in vitro. In vivo studies showed enhancement of the survival of laser immunotherapy-treated rats bearing metastatic mammary tumors. Our in vitro and in vivo results indicated that GC was a strong immunological stimulant. Its non-toxic nature and immunological activity make GC a potential immunoadjuvant for treatment of metastatic tumors.
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