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An acellular tissue matrix-based drug carriers with dual chemo-agents for T colon cancer growth suppression
Changfu Qin, Yingmo Shen, Baoshan Wang, Xuefei Zhao, Yiting Liu, Shuo Yang, Jie Chen
Department of Hernia and abdominal wall surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China
Background/aims: Relapse, metastasis, and chemo-resistance are the main factors responsible for the failure of surgical treatment of malignant tumors, and typically are the main obstacles to effective cancer treatment. Although significant advances have been made in the field of cancer chemotherapy, many patients still receive inadequate treatment due to the severe adverse effects of these drugs, resulting in an inability to reach ther-apeutic concentrations at the tumor site with systemic chemotherapy. Thus, a biological patch loaded with chemotherapeutic drugs could be an ideal strategy for the treatment of cancer at the tumor site.
Methods: We developed an acellular matrix using the submucosa of porcine jejunum, then loaded this matrix with different amounts of 5-fluorouracil (5-FU) and rapamycin nanoparticles. Cell proliferation and apoptosis were analyzed by flow cytometry and related markers were evaluated using real-time PCR and western blotting. The patches were evaluated in vitro to characterize their release kinetics and therapeutic feasibility. We then analyzed the therapeutic efficacy and systemic toxicity of these patches in vivo by using them in a mouse model of colon cancer. Results: The patches delivered 5-FU and rapamycin in a controlled manner for more than 8 weeks, arrested the cell cycle of LoVo cells and sw480 cells at G2/M phase, and induced apoptosis in vitro. The patches also sup-pressed the growth of xenografted tumors in vivo with lower adverse effects than typically observed with sys-temic administration of these drugs.
Conclusion: We demonstrated that patches loaded with 5-FU-RAPA-PLA-NP significantly inhibited the growth of colon cancer in vitro and in vivo. These results demonstrated the feasibility of the use of a multi-effect biological patch for cancer treatment.
Cancer is a genetic disease characterized by uncontrolled cell growth and invasion of cancer cells into proximal and distal tissues via the lymphatic system and the blood, a process termed metastasis.  Although significant advances have been made in the field of cancer therapy including surgery, chemotherapy, and radiation, many patients receive unsatisfactory cancer treatment due to relapse or the severe adverse effects of drugs [1,2].
Chemotherapy can be administered before or after resection of tu-mors to suppress tumor growth or prevent recurrent growth and me-tastasis of remaining malignant cells. Most chemotherapeutic drugs, such as 5-fluorouracil (5-FU), cisplatin, paclitaxel, and rapamycin and its analogs, are commonly used for treatment of a range of cancers.