System Used:
IVIM System
M-Series
Guolin Zhao, William Ho, Jinxian Chu, Xiaojian Xiong, Bin Hu, Kofi Oti Boakye-Yiadom, Xiaoyang Xu,* and Xue-Qing Zhang*.
Lung cancer is extremely deadly, causing about 1.8 million deaths in 2020. Most lung cancer patients (over 85%) have a type called non-small-cell lung cancer (NSCLC), and in about one-third of these cases, there’s a mutation in the KRAS gene. This mutation leads to constant cell growth and tumor formation, making the cancer hard to treat and resulting in poor patient outcomes.
Researchers have tried to create drugs that block the KRAS gene’s function, but these treatments have faced many challenges, such as the development of resistance and potential harm to healthy tissues. This means there’s a significant need for better treatments that can target KRAS mutations without causing widespread damage.
One promising approach involves using small-interfering RNA (siRNA) to target and silence the mutant KRAS gene. However, delivering these siRNA treatments specifically to lung tumors is difficult. Many delivery systems, like lipid-based nanocarriers, have been developed, but they often struggle to target the lungs effectively and can cause harmful side effects. Improving these delivery systems is crucial for making gene therapies a viable option for treating lung cancer and other lung diseases.
Figure 1. Schematic illustration of inhalable siKRAS@GCLPP NPs for suppressing KRAS-mutant NSCLC. The design of siKRAS@GCLPP NPs include (i) a cationic lipid-like molecule designated as G0-C14 entraps siRNA candidates and facilitates endosome escape,25,30 (ii) a biodegradable PLGA-PEG acting as a matrix protecting the encapsulated siRNA during nebulization, and (iii) [D-Lys6]-LHRH conjugated to the end of the PEG molecule for binding to the LHRH receptors, which are overexpressed on the tumor cell membrane.