Page 253 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-70

Plant-derived exosome-like nanovesicles: Arctium lappa L.-derived

nanovesicles induce pyroptosis of lung carcinoma cells in vivo and in vitro

1,2
1,2
1,2
Jae Heon Sim, #,1,2 Mina Boo, Hyunyoung Choi, Suhyeon An, HyunSoo Yang,
1,2
2
Dong-Hyun Youn, Hye-Lin Kim, Jinbong Park* ,2
2

1 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul,
Republic of Korea
2 Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul,
Republic of Korea
* E-mail: thejinbong@khu.ac.kr

Abstract
Plant-derived exosome-like nanovesicles have recently emerged as promising natural
therapeutics due to their biocompatibility, stability, and capacity to transport diverse bioactive
molecules. In this study, we investigated the anti-cancer efficacy of Arctium lappa L.-derived
exosome-like nanovesicles (ALDENs), with a particular focus on their ability to induce
pyroptosis in lung carcinoma. In vitro, treatment of murine Lewis lung carcinoma (LLC1) cells
with ALDENs triggered robust activation of the NOD-like receptor family pyrin domain
containing 3inflammasome (NLRP3), leading to caspase-1 activation, gasdermin D (GSDMD)
cleavage, and consequent pyroptotic cell death. These processes were accompanied by a
significant increase in Interleukin-1 beta (IL-1β) secretion and elevated lactate dehydrogenase
(LDH) release, consistent with pyroptotic activity. Immunofluorescence analysis further
confirmed enhanced expression and co-localization of ASC and NLRP3 in LLC1 cells
following ALDENs treatment. In vivo, subcutaneous implantation of LLC1 cells in C57BL/6
mice followed by oral administration of ALDENs significantly suppressed tumor growth and
reduced tumor burden compared with control groups. Importantly, immunofluorescence
staining of tumor tissues revealed upregulated Apoptosis-associated speck-like protein
containing a CARD (ASC) and NLRP3 expression within the tumor microenvironment,
indicating inflammasome activation in vivo. No evidence of hepatic or renal toxicity was
observed, supporting the favorable safety profile of ALDENs. In result, these findings identify
ALDENs as a safe, plant-derived nanotherapeutic capable of exerting anti-tumor activity by
inducing inflammasome-dependent pyroptosis. The novelty of this work lies in demonstrating
that orally delivered plant-derived nanovesicles can activate pyroptotic cell death both in vitro
and in vivo, thereby positioning ALDENs as a promising natural therapeutic strategy for the
treatment of solid tumors such as lung carcinoma.

Keywords: Arctium lappa; Plant-derived exosome-like nanovesicles; Pyroptosis; Lung cancer