Intravesical delivery of KDM6A -mRNA via mucoadhesive nanoparticles inhibits the metastasis of bladder cancer

• DOI: 10.1073/pnas.2112696119
• Publication Date: 2022-02-07T21:27:11Z
• Authors: Na Kong; Ruonan Zhang; Gongwei Wu; Xinbing Sui; Junqing Wang; Na Yoon Kim; Sara Blake; Diba De; Tian Xie; Yihai Cao; Wei Tao
• Keywords: Histone Demethylases; 0301 basic medicine; Mucous Membrane; Adhesiveness; Mice, Nude; Genetic Therapy; Neoplasms, Experimental; Biological Sciences; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Administration, Intravesical; Urinary Bladder Neoplasms; Cell Line, Tumor; Animals; Humans; Nanoparticles; RNA, Messenger; Neoplasm Metastasis

Lysine-specific demethylase 6A (KDM6A), also named UTX, is frequently mutated in bladder cancer (BCa). Although known as a tumor suppressor, KDM6A's therapeutic potential the metastasis of BCa remains elusive. It difficult to fulfill effective up-regulation KDM6A levels tissues situ verify its treating metastasis. Here, we report mucoadhesive messenger RNA (mRNA) nanoparticle (NP) strategy for intravesical delivery KDM6A-mRNA mice bearing orthotopic Kdm6a-null and show evidence inhibiting BCa. Through this mRNA NP strategy, exposure tumors can be greatly prolonged expression, penetration enhanced by adhering sustained delivery. This demonstrated combination therapy with other clinically approved drugs (e.g., elemene), which could further enhance outcomes. Our findings not only via but provide proof-of-concept usefulness these NPs tools both mechanistic understanding translational study bladder-related diseases.