Tumor Cell Dissociation Removes Malignant Bladder Tumors

Surgery and subsequent chemotherapy are still the most adopted clinical modalities for bladder cancer treatments with the inevitable operation risks, chemotherapy toxicity, and high recurrence rate. Here, we report an unprecedented tumor cell dissociation strategy for malignant bladder tumor removal without the needs of conventional surgery and chemotherapy. A common metal ion chelator, ethylene diamine tetraacetic acid (EDTA), has been loaded into the interlayers of neurotensin (NT)-modified Zn-Al layered double hydroxide (LDH). Under the targeting by NT, such a nano-platform shows high affinity to bladder tumor cells, leading to the highly selective and efficient accumulation at the bladder tumor site. The released EDTA molecules deprive Ca²⁺ from the intercellular calcium-dependent connexin by EDTA-Ca²⁺ chelation, resulting in the tumor disaggregation that is then safely excreted out of body rather than killed using toxic chemodrugs, thus, ensuring excellent biosafety and extraordinarily high effectiveness. Surgery and subsequent chemotherapy are still the most adopted clinical modalities for bladder cancer. Because of operation risks, chemotherapy toxicity, and high recurrence rate, these treatment outcomes and prognosis remain rather poor. Here, we report a feasible, mild but effective bladder cancer treatment modality by a tumor cell dissociation strategy. In detail, a nano-platform was synthesized by loading ethylene diamine tetraacetic acid (EDTA) into the interlayers of neurotensin (NT)-modified layered double hydroxide (LDH). Such a nano-platform leads to the selective accumulation at bladder tumor site and releases EDTA where the resulting tumor cells are dissociated and excreted through urine excretion. Moreover, the detached cells hardly invade normal tissues in a rat model due to the prevailing attachment of the nanosheets on cancer cell membranes. Such a strategy without tumor reoccurrence and metastasis in the treatment brings good news for bladder cancer patients. A nano-platform (NT-LDH/EDTA) has been constructed, which shows high affinity to bladder tumor cells and releases EDTA molecules at the tumor site; as a result, the cancer cells are mildly dissociated and then expelled out of the body through urine excretion rather than killed using toxic chemodrugs.