Li Man, Bao Qunqun, Guo Jing, Xie Ruting, Shen Chao, Wei Qing, Hu Ping, Qin Huanlong, Shi Jianlin
Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200072, P.R. China.
Department of Pathology, Shanghai Tenth People's Hospital, 301 Yan-chang Road, Shanghai 200072, P. R. China.
Nano Lett. 2022 Apr 13;22(7):2769-2779. doi: 10.1021/acs.nanolett.1c04797. Epub 2022 Mar 25.
Treatments for low colorectal cancer (CRC) remain a great challenge due to the heavy physical and psychological burdens of colostomy, strong drug toxicity in chemotherapy, and myelosuppression-/chemoradiation-related gastrointestinal symptoms. In this study, a highly biosafe and effective tumor cell dissociation-based low CRC treatment modality has been verified on both PDOs and colorectal tumor models . Notably, controllable EDTA release at the tumor sites was achieved by the LDH degradation in response to a slightly acidic microenvironment of low CRC tumors. Resultantly, the intratumoral E-cadherin for intercellular junctions of low CRC tumors was effectively destroyed via Ca depletion by released EDTA from the interlayers, initiating remarkable tumor cell dissociation and resultant tumor disaggregation/removal via defecation. Dissociated tumor cells were prevailingly enveloped by LDH/EDTA, which prevented them from readhering to adjacent tissues, providing an unprecedented, efficient and safe therapeutic modality for low CRC, which will benefit patients suffering low CRC.
由于结肠造口术带来的沉重身心负担、化疗中强烈的药物毒性以及骨髓抑制和放化疗相关的胃肠道症状，低位结直肠癌（CRC）的治疗仍然是一个巨大的挑战。在本研究中，一种基于肿瘤细胞解离的高度生物安全且有效的低位CRC治疗模式已在患者来源的肿瘤组织（PDO）和结直肠肿瘤模型上得到验证。值得注意的是，通过层状双氢氧化物（LDH）在低位CRC肿瘤微酸性环境下的降解，实现了肿瘤部位可控的乙二胺四乙酸（EDTA）释放。结果，通过层间释放的EDTA导致的钙耗竭，低位CRC肿瘤细胞间连接的肿瘤内E-钙黏蛋白被有效破坏，引发显著的肿瘤细胞解离，并通过排便导致肿瘤解体/清除。解离的肿瘤细胞主要被LDH/EDTA包裹，这阻止了它们重新黏附到相邻组织，为低位CRC提供了一种前所未有的、高效且安全的治疗模式，这将使患有低位CRC的患者受益。
