[Sportschosun Reporter Jang Jong-ho] An inhalable nanotherapy has been developed that delivers anticancer drugs directly to the lungs, attacks lung cancer cells, and simultaneously modulates immune cells that help tumors grow.
The achievement came from a joint research team led by Professor Kim Hyun-gu of the Department of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital and Professor Ji Ho Park of the Department of Bio and Brain Engineering at Korea Advanced Institute of Science and Technology (KAIST). The team also included Dr. Kim Kyung-soo of Korea Institute of Science and Technology (KIST), researcher Jeon Eun-bi and Professor Lee Jun-hee of the Department of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital.
Inhalable therapies that deliver anticancer drugs directly to the lungs are being studied as a new treatment option because they can concentrate drugs at the site of a lesion. However, the particles can become unstable during the process of formulating the drugs for inhalation, and they may be rapidly eliminated by immune cells after reaching the lungs. These limitations have made it difficult to keep the drugs in the lungs for a sufficient period of time. As a result, a treatment strategy was needed to keep the drugs in the lungs longer and deliver them effectively to cancer cells.
To address these challenges, the research team developed inhalable nanoparticles using pulmonary surfactant, a substance naturally present in the lungs. The nanoparticles were loaded with paclitaxel, an anticancer drug, while pemetrexed was attached to their surface to target folate receptors. In this study, pemetrexed was used primarily not as an anticancer drug but as a targeting agent that seeks out lung cancer cells and certain tumor-associated macrophages with high folate receptor expression. The team then analyzed the nanotherapy's delivery and anticancer effects in lung cancer cells and immune cells.
The experiments showed that the nanotherapy was effectively taken up by lung cancer cells, reducing their survival rate. Notably, it targeted not only cancer cells but also immune cells that help tumors grow. M2-type macrophages are present around tumors and promote cancer cell growth while helping cancer cells evade immune attacks. The nanotherapy was also effectively delivered to these cells.
Furthermore, after treatment, the characteristics of M2-type macrophages that support cancer growth decreased, while characteristics similar to those of M1-type macrophages, which help activate immune responses against cancer, increased. In other words, the findings confirmed the possibility that the therapy could do more than directly attack lung cancer cells; it could also change the surrounding immune environment that had supported tumor growth into one that suppresses cancer.
To determine whether these effects would also occur in living organisms, the research team divided mice with lung cancer into four groups: a no-treatment control group, a standard paclitaxel treatment group, a comparator nanoparticle group treated with PLGA nanoparticles, and a group treated with the newly developed nanotherapy. The team analyzed changes in tumors, the drugs' distribution in the body, and systemic toxicity.
The newly developed nanoparticles remained in the lungs for up to 48 hours, while only small amounts spread to other organs. After three weeks of treatment, tumor growth was more strongly suppressed than in the groups treated with standard paclitaxel or comparator nanoparticles. During the observation period, five of eight mice in the control group, four of eight in the standard paclitaxel group, and three of eight in the comparator nanoparticle group died. The treatment group had the fewest deaths, with one of eight mice dying.
Around the tumors, immune responses that promote cancer growth decreased, while immune responses against cancer increased. Changes in macrophages consistent with those observed in the earlier cell experiments were also confirmed in the tumor tissue. No clear systemic toxicity was observed in major organs, including the liver, heart, and kidneys, or in blood tests. These results show that keeping anticancer drugs in the lungs longer may enhance treatment efficacy while reducing harmful effects on other organs.
Professor Kim Hyun-gu said, "In lung cancer treatment, it is important to deliver anticancer drugs sufficiently to the tumor while reducing exposure and side effects in healthy organs." He added, "This study is significant because, at the preclinical stage, it confirmed the potential of an inhalable platform that uses the lungs' physiological environment to simultaneously target lung cancer cells and the tumor immune microenvironment."
Meanwhile, the study was published in the international journal Journal of Nanobiotechnology under the title "Pulmonary surfactant-based inhalable nanoparticles for folate receptor-targeted delivery and macrophage reprogramming in lung cancer."
Reporter Jang Jong-ho bellho@sportschosun.com
This article has been translated by GripLabs Mingo AI.
