TY - JOUR

T1 - Inhaled RNA drugs to treat lung diseases

T2 - Disease-related cells and nano–bio interactions

AU - Zhang, Mengjun

AU - Lu, Haoyu

AU - Xie, Liangkun

AU - Liu, Xulu

AU - Cun, Dongmei

AU - Yang, Mingshi

N1 - Publisher Copyright: © 2023 Elsevier B.V.

PY - 2023

Y1 - 2023

N2 - In recent years, RNA-based therapies have gained much attention as biomedicines due to their remarkable therapeutic effects with high specificity and potency. Lung diseases offer a variety of currently undruggable but attractive targets that could potentially be treated with RNA drugs. Inhaled RNA drugs for the treatment of lung diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome, have attracted more and more attention. A variety of novel nanoformulations have been designed and attempted for the delivery of RNA drugs to the lung via inhalation. However, the delivery of RNA drugs via inhalation poses several challenges. It includes protection of the stability of RNA molecules, overcoming biological barriers such as mucus and cell membrane to the delivery of RNA molecules to the targeted cytoplasm, escaping endosomal entrapment, and circumventing unwanted immune response etc. To address these challenges, ongoing researches focus on developing innovative nanoparticles to enhance the stability of RNA molecules, improve cellular targeting, enhance cellular uptake and endosomal escape to achieve precise delivery of RNA drugs to the intended lung cells while avoiding unwanted nano–bio interactions and off-target effects. The present review first addresses the pathologic hallmarks of different lung diseases, disease-related cell types in the lung, and promising therapeutic targets in these lung cells. Subsequently we highlight the importance of the nano–bio interactions in the lung that need to be addressed to realize disease-related cell-specific delivery of inhaled RNA drugs. This is followed by a review on the physical and chemical characteristics of inhaled nanoformulations that influence the nano–bio interactions with a focus on surface functionalization. Finally, the challenges in the development of inhaled nanomedicines and some key aspects that need to be considered in the development of future inhaled RNA drugs are discussed.

AB - In recent years, RNA-based therapies have gained much attention as biomedicines due to their remarkable therapeutic effects with high specificity and potency. Lung diseases offer a variety of currently undruggable but attractive targets that could potentially be treated with RNA drugs. Inhaled RNA drugs for the treatment of lung diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome, have attracted more and more attention. A variety of novel nanoformulations have been designed and attempted for the delivery of RNA drugs to the lung via inhalation. However, the delivery of RNA drugs via inhalation poses several challenges. It includes protection of the stability of RNA molecules, overcoming biological barriers such as mucus and cell membrane to the delivery of RNA molecules to the targeted cytoplasm, escaping endosomal entrapment, and circumventing unwanted immune response etc. To address these challenges, ongoing researches focus on developing innovative nanoparticles to enhance the stability of RNA molecules, improve cellular targeting, enhance cellular uptake and endosomal escape to achieve precise delivery of RNA drugs to the intended lung cells while avoiding unwanted nano–bio interactions and off-target effects. The present review first addresses the pathologic hallmarks of different lung diseases, disease-related cell types in the lung, and promising therapeutic targets in these lung cells. Subsequently we highlight the importance of the nano–bio interactions in the lung that need to be addressed to realize disease-related cell-specific delivery of inhaled RNA drugs. This is followed by a review on the physical and chemical characteristics of inhaled nanoformulations that influence the nano–bio interactions with a focus on surface functionalization. Finally, the challenges in the development of inhaled nanomedicines and some key aspects that need to be considered in the development of future inhaled RNA drugs are discussed.

KW - Inhalation

KW - Lung diseases

KW - Nano–bio interactions

KW - RNA drugs

U2 - 10.1016/j.addr.2023.115144

DO - 10.1016/j.addr.2023.115144

M3 - Review

C2 - 37995899

AN - SCOPUS:85179014727

VL - 203

JO - Advanced Drug Delivery Reviews

JF - Advanced Drug Delivery Reviews

SN - 0169-409X

M1 - 115144

ER -