Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy West China Hospital, Sichuan University, Chengdu, 610041, China.
Adv Sci (Weinh). 2024 Sep;11(33):e2404800. doi: 10.1002/advs.202404800. Epub 2024 Jun 27.
The treatment of colorectal cancer is always a major challenge in the field of cancer research. The number of estimated new cases of colorectal cancer worldwide in 2020 is 1 148 515, and the estimated number of deaths is 576 858, revealing that mortality accounted for approximately half of the disease incidence. The development of new drugs and strategies for colorectal cancer treatment is urgently needed. Thermosensitive injectable hydrogel PDLLA-PEG-PDLLA (PLEL) loaded with cabazitaxel (CTX) is used to explore its anti-tumor effect on mice with orthotopic colorectal cancer. CTX/PLEL is characterized by a solution state at room temperature and a hydrogel state at physiologic temperature. The excipients MPEG-PCL and PDLLA-PEG-PDLLA have good biocompatibility and biodegradability. The simple material synthesis and preparation process renders this system cost-effective and more conducive to clinical transformation. An orthotopic colorectal cancer model is established by transplantation subcutaneous tumors onto the cecum of mice. According to the results of experiments in vivo, CTX/PLEL significantly inhibits orthotopic colorectal cancer and liver metastasis in mice. The results indicate that CTX/PLEL nanoparticle preparations have high security and excellent anti-tumor effects, and have great application potential in colorectal cancer therapy.
结直肠癌的治疗一直是癌症研究领域的重大挑战。2020 年全球估计有 1148515 例结直肠癌新发病例，估计死亡人数为 576858 例，这表明死亡率约占该病发病率的一半。迫切需要开发治疗结直肠癌的新药和策略。载多西紫杉醇（CTX）的温敏注射水凝胶 PDLLA-PEG-PDLLA（PLEL）用于探索其对原位结直肠癌小鼠的抗肿瘤作用。CTX/PLEL 的特点是在室温下为溶液状态，在生理温度下为水凝胶状态。赋形剂 MPEG-PCL 和 PDLLA-PEG-PDLLA 具有良好的生物相容性和可生物降解性。该系统的简单材料合成和制备工艺具有成本效益，更有利于临床转化。通过将皮下肿瘤移植到小鼠的盲肠中来建立原位结直肠癌模型。根据体内实验结果，CTX/PLEL 显著抑制了小鼠的原位结直肠癌和肝转移。结果表明，CTX/PLEL 纳米颗粒制剂具有很高的安全性和优异的抗肿瘤作用，在结直肠癌治疗中有很大的应用潜力。
