Intravesical delivery of <i>KDM6A</i> -mRNA via mucoadhesive nanoparticles inhibits the metastasis of bladder cancer-Reference-Cited by-同舟云学术

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

Published:2022-02-07 Issue:7 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Kong Na¹²³⁴,Zhang Ruonan¹²,Wu Gongwei⁵^ORCID,Sui Xinbing¹²,Wang Junqing⁴,Kim Na Yoon⁴,Blake Sara⁴,De Diba⁴,Xie Tian¹²⁶,Cao Yihai⁷^ORCID,Tao Wei⁴^ORCID

Affiliation:

1. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China

2. Department of Medical Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China

3. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China

4. Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

5. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215

6. Key Laboratory of Elemene Class Anti-Cancer Medicines, Engineering Laboratory of Development of Chinese Medicines, and Collaborative Innovation Center of Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China

7. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden

Abstract

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.

Funder

Natural Science Foundation of Zhejiang Province

National Natural Science Foundation of China

METAvivor

Brigham and Women''''s Hospital

Zhejiang Province Science and Technology Project of TCM

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2112696119