载抗癌转移siRNA和抗增殖阿霉素的多功能纳米药物及其联合抗癌作用研究

Tumor proliferation and metastasis are the leading causes of cancer patients’death. By exploiting the physiological-biochemical and anatomic characteristics of tumor and tumor metastasis-related NF-κB signal paths, we firstly design, prepare and study a multifunctional antitumor nanomedicine of RGD-PEG-DSPEI-GNR/DOX/siRNA with high efficiency and low toxicity which has tumor active and passive targeting, contains anti-tumor metastasis siRNA and anti-tumor proliferation doxorubicin, presents an intracellular responsive drug release profile and gold nanorod’s photothermal effect. Glutathione and pH responsive drug release as well as near Infrared thermal effect are investigated. By using high metastasis human breast cancer MDA-MB-435 and the MDA-MB-435 bearing mice as animal models, we study and evaluate the tumor targeting ability, anti-tumor metastasis and proliferation effects and possible mechanism, compare gene therapy, chemotherapy and photothermal therapy as well as the effects of drug combination on anti-tumor metastasis and proliferation. The results can provide a new idea, new approach and scientific basis for developing novel antitumor nanomedicines.

肿瘤增殖和转移是导致癌症患者死亡的主要原因。针对肿瘤不同于健康组织的生理生化和解剖特征以及与肿瘤转移相关的NF-κB信号通道，本项目首次设计、制备和研究一种新型高效低毒的多功能抗肿瘤纳米药物RGD-PEG-DSPEI-GNR/DOX/siRNA，该纳米药物集EPR效应引起的肿瘤被动靶向性和RGD穿膜肽赋予的肿瘤主动靶向性、沉默p65表达以阻断NF-κB信号通道的抗肿瘤转移小干扰RNA药物和抗肿瘤增殖化疗药物阿霉素同时负载、细胞内响应性释药以及金纳米棒载体独特的光热特性于一体；考察纳米药物谷胱甘肽和pH响应性释药行为和近红外光致热效应；以高转移性人乳腺癌MDA-MB-435细胞株及其原位接种裸鼠模型体内外评价和研究该纳米药物抗肿瘤转移和增殖的作用及其机制；比较基因治疗、化疗和光热治疗及其联合应用对抗肿瘤转移和增殖影响。本项目研究结果将为新型抗肿瘤纳米药物的研发提供新思路、新方法及科学依据。

肿瘤增殖和转移是导致癌症患者死亡的主要原因。针对肿瘤不同于健康组织的生理生化和解剖特征以及与肿瘤转移相关的NF-κB信号通道，本项目首次设计、制备和研究一种新型高效低毒的多功能抗肿瘤纳米药物RGD-PEG-DSPEI-GNR/DOX/siRNA，该纳米药物集EPR效应引起的肿瘤被动靶向性和RGD穿膜肽赋予的肿瘤主动靶向性、沉默p65表达以阻断NF-κB信号通道的抗肿瘤转移小干扰RNA药物和抗肿瘤增殖化疗药物阿霉素同时负载、细胞内响应性释药以及金纳米棒载体独特的光热特性于一体；考察纳米药物谷胱甘肽和pH响应性释药行为和近红外光致热效应；以高转移性人乳腺癌MDA-MB-435细胞株及其原位接种裸鼠模型体内外评价和研究该纳米药物抗肿瘤转移和增殖的作用及其机制；比较基因治疗、化疗和光热治疗及其联合应用对抗肿瘤转移和增殖影响。本项目研究结果将为新型抗肿瘤纳米药物的研发提供新思路、新方法及科学依据。