Direct Delivery to Lungs and Retention for Up to 48 Hours: Inhalable Nano-Therapeutic for Lung Cancer Developed

Overcoming Limitations of Lung Drug Delivery in Conventional Cancer Therapies
Tumor Growth Suppression Demonstrated in Animal Studies

A new inhalable nano-therapeutic, developed by a team of Korean researchers, addresses the limitations of traditional anti-cancer therapies in delivering drugs to the lungs, while simultaneously targeting both lung cancer cells and immune cells that promote tumor growth.

From the left, Hyungoo Kim, Professor of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital; Jiho Park, Professor of Bio and Brain Engineering at KAIST; Kyungsoo Kim, PhD at KIST; Eunbi Jeon, Researcher of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital; Junhee Lee, Professor of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital. Korea University Guro Hospital

Korea University Guro Hospital announced on September 30 that a collaborative research team led by Hyungoo Kim, Professor of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital, and Jiho Park, Professor of Bio and Brain Engineering at KAIST, (including Kyungsu Kim, Researcher at KIST; Eunbi Jeon, Researcher of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital; and Junhee Lee, Professor of Cardiovascular and Thoracic Surgery at Korea University Guro Hospital) has developed an inhalable nanoparticle that delivers anti-cancer agents directly to the lungs by leveraging pulmonary surfactant, which naturally exists in the lungs.

In lung cancer treatment, the systemic administration of anti-cancer agents through intravenous injection can expose normal organs as well as cancer cells to these drugs, creating a significant limitation. While inhalable therapeutics can deliver medication directly to the lungs—raising local drug concentration and reducing systemic exposure—they have faced the challenge of nano-particles being rapidly removed by immune cells once inside the lung.

To address this, the research team created nanoparticles based on pulmonary surfactant and loaded the anti-cancer drug paclitaxel inside. The nanoparticle surface is conjugated with pemetrexed, thereby enabling targeted delivery to lung cancer cells and specific tumor-associated macrophages that highly express folate receptors.

This therapy is noteworthy for targeting not only cancer cells but also the immune microenvironment around tumors. After the nanoparticles were delivered to M2-type macrophages—which support tumor growth and suppress immune responses—the characteristics of these M2-type macrophages decreased, while the traits of M1-type macrophages, which help anti-tumor immunity, were enhanced.

In experiments conducted on mice with lung cancer, the inhaled nanoparticles remained in the lungs for up to 48 hours, with limited transfer to other organs. After three weeks of treatment, tumor growth was more suppressed in the group receiving the developed nanoparticles than in both the standard paclitaxel group and the comparative nanoparticle group.

There were also differences in survival rates. During the experiment, five out of eight mice died in the untreated control group, four in the standard paclitaxel group, and three in the comparative nanoparticle group, whereas only one mouse died in the group treated with the new nano-therapeutic. No apparent systemic toxicity was observed in major organs or blood tests, including liver, heart, and kidney.

Professor Hyungoo Kim stated, "In lung cancer treatment, it is crucial to deliver enough anti-cancer drugs to the tumor site while minimizing exposure and side effects to normal organs. The significance of this study lies in confirming, at the preclinical stage, the potential of an inhalable platform that leverages the lung's physiological environment to simultaneously attack lung cancer cells and the tumor’s immune microenvironment."

This research was published in the international journal 'Journal of Nanobiotechnology' under the title 'Pulmonary Surfactant-Based Inhalable Nanoparticles for Folate Receptor-Targeted Drug Delivery and Macrophage Reprogramming in Lung Cancer.'

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