当前结肠癌临床化疗遇到药效差、毒副作用大的瓶颈，提高结肠癌的口服化疗敏感性成为攻克该瓶颈的关键。CD98在结肠癌的发生和发展过程中起重要作用，但至今还没有研究揭示其在结肠癌治疗中的地位。申请人在CD98研究和结肠癌化疗的研究基础上提出：沉默CD98表达是提高结肠癌口服化疗敏感性的有效新途径。本课题组已经完成了这一具有创新性研究的论证工作，并且取得了较好的结果：初步证实了提高结肠癌化疗敏感性可以通过沉默CD98基因表达来获得。进一步将系统研究CD98 抗体Fab'片段功能化共载CD98 siRNA（siCD98）/喜树碱纳米粒子的制备工艺；研究不同浓度siCD98对结肠癌化疗增敏效应的影响；基于原位结肠癌小鼠模型研究靶向共载纳米粒子/水凝胶口服给药系统的体内疗效、增敏分子机制、药代动力学及毒副作用。通过本项目实施不仅能探明CD98在结肠癌化疗中的地位，而且还有望解决结肠癌临床化疗的瓶颈问题。

Currently, clinical colon cancer chemotherapy has been extremely stymied by poor efficacy and seriously toxic side-effect. CD98 plays an important role in the occurrence and development of colon cancer. However, its therapeutic role in colon cancer treatment has not been elucidated. On the basis of our CD98-related research and colon cancer therapy study, we proposed that the inhibition of CD98 expression is a novel efficient approach to promote the oral chemosensitization in colon cancer therapy. Our group has completed the feasibility studies for this innovative research. Initial results indicated that the promotion of colon cancer chemosensitization can be achieved by inhibition of CD98 expression. Further studies will focus on the systematic investigation of fabrication parameters of CD98 Fab'-functionalized CD98 siRNA (siCD98)/camptothecin-loaded nanoparticles; Investigation of the colon cancer chemosensitization effect of siCD98 with various concentrations; Investigation of in vivo therapeutic efficacy, chemosensitization mechanism, pharmacokinetics and toxic side effect of our targeted drug delivery nanoparticles/hydrogel system based on orthotopic colon cancer mouse model. Implementation of this project will not only elucidate the beneficial role of CD98 in colon cancer chemotherapy, but also solve the bottleneck problems in clinical colon cancer treatment.