Open AccessIntravesical delivery of KDM6A -mRNA via mucoadhesive nanoparticles inhibits the metastasis of bladder cancer
Author(s) -
Na Kong,
Ruonan Zhang,
Gongwei Wu,
Xinbing Sui,
Junqing Wang,
Na Yoon Kim,
Sara Blake,
Diba De,
Tian Xie,
Yihai Cao,
Wei Tao
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2112696119
Subject(s) - messenger rna , bladder cancer , cancer research , metastasis , gene knockdown , medicine , cancer , chemistry , apoptosis , biochemistry , gene
Significance This study provides proof-of-principle evidence for intravesical delivery of messenger RNA (mRNA) via a mucoadhesive nanoparticle (NP) strategy and reveals the therapeutic potential of KDM6A in treating bladder cancer metastasis, which remains difficult due to the physiological bladder barriers. The mucoadhesive NPs could protect loaded mRNA, prolong exposure of mRNA in disease sites, and benefit the penetration and effective expression, which all represent challenging hurdles for intravesical delivery of mRNA therapeutics. mRNA local delivery can also avoid potential toxicity issues via systemic delivery and unwanted protein expression throughout the body. We expect this mucoadhesive mRNA nanotechnology can be useful for the effective up-regulation of targeted proteins in bladder tissues in situ for both mechanistic understanding and translational study of bladder-related diseases.