Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Biomaterials. 2015 May;51:161-172. doi: 10.1016/j.biomaterials.2015.02.002. Epub 2015 Feb 19.
As a synergistic drug combination, doxorubicin-loaded cisplatin crosslinked polysaccharide-based nanoparticles (Dex-SA-DOX-CDDP) have demonstrated enhanced antitumor efficacy and reduced systemic toxicity via optimized biodistribution, controlled drug release, prolonged blood circulation, and improved tolerability, compared to the non-crosslinked nanoparticles or free doxorubicin. Herein, we apply the Dex-SA-DOX-CDDP nanoparticles as an efficient antitumor agent to treat colorectal and breast tumors in three different in vivo models, i.e. subcutaneously implanted colorectal carcinoma, dimethylhydrazine-induced autochthonous colorectal carcinoma, and metastatic mammary carcinoma, which more closely simulate the natural milieu of the original tumor with intact pathological and immunological responses. Based on the properties of this combination in higher tumor accumulation and penetrating efficiency, the Dex-SA-DOX-CDDP nanoparticles significantly decreased the tumor sizes in CT26 cell line xenograft tumors compared to control. In addition, the affected animals' lifespan was significantly extended after the Dex-SA-DOX-CDDP treatment, in the autochthonous colon cancer model. Moreover, with the aid of iRGD, Dex-SA-DOX-CDDP could effectively block primary tumor growth and prevent the metastasis of 4T1 murine mammary carcinoma. In conclusion, Dex-SA-DOX-CDDP nanoparticles remarkably inhibit growth of colorectal carcinoma and metastasis of mammary carcinoma in vivo, which provides potential application as a safe and efficient antitumor agent in treatment of these cancers.
作为一种协同药物组合，载多柔比星顺铂交联多糖纳米粒（Dex-SA-DOX-CDDP）通过优化的生物分布、控制药物释放、延长血液循环和提高耐受性，与非交联纳米粒或游离多柔比星相比，显示出增强的抗肿瘤疗效和降低的全身毒性。在此，我们将 Dex-SA-DOX-CDDP 纳米粒作为一种有效的抗肿瘤剂，用于治疗三种不同的体内模型中的结直肠癌和乳腺癌，即皮下植入的结直肠癌细胞癌、二甲基肼诱导的同源结直肠癌细胞癌和转移性乳腺癌细胞癌，这些模型更紧密地模拟了具有完整病理和免疫反应的原始肿瘤的自然环境。基于该组合在更高的肿瘤积累和穿透效率的特性，与对照组相比，Dex-SA-DOX-CDDP 纳米粒显著减小了 CT26 细胞系异种移植肿瘤的肿瘤大小。此外，在同源结肠癌模型中，Dex-SA-DOX-CDDP 治疗后，受影响动物的寿命显著延长。此外，在 iRGD 的辅助下，Dex-SA-DOX-CDDP 可以有效地阻断原发性肿瘤的生长并防止 4T1 鼠乳腺癌细胞的转移。总之，Dex-SA-DOX-CDDP 纳米粒显著抑制结直肠癌和乳腺癌在体内的生长和转移，为其作为治疗这些癌症的安全有效的抗肿瘤剂提供了潜在的应用。
