pH-sensitive multi-drug liposomes targeting folate receptor β for efficient treatment of non-small cell lung cancer.


Park YI(1), Kwon SH(2), Lee G(1), Motoyama K(3), Kim MW(4), Lin M(5), Niidome T(6), Choi JH(7), Lee R(8).
Author information:
(1)School of Chemical Engineering, Chonnam National University, Gwangju 61186, Republic of Korea.
(2)Korea Basic Science Institute, Seoul 02841, Republic of Korea.
(3)Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
(4)International Research Organization for Advanced Science and Technology
(IROAST), Kumamoto University, Kumamoto 860-8555, Japan.
(5)The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
(6)Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan.
(7)Department of Anatomy & Institute of Veterinary Science, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: [Email]
(8)International Research Organization for Advanced Science and Technology
(IROAST), Kumamoto University, Kumamoto 860-8555, Japan. Electronic address: [Email]


Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer-related deaths worldwide. Tumor-associated macrophages (TAMs), which can be polarized into tumor-promoting M2 phenotype, overexpress folate receptor beta (FRβ) and are associated with poor prognosis in NSCLC. In addition, calpain-2 (CAPN2) is overexpressed in NSCLC and is involved in tumor growth. To improve the anticancer efficacy of drugs and reduce their side effects in the treatment of NSCLC, it is important to develop smart drug delivery systems with specific targeting ability and controlled release mechanisms. In this study, FRβ-targeted pH-sensitive liposomes were designed as carriers to ensure efficient drug delivery and acid-responsive release in NSCLC cells. Folate-mediated targeting of FRβ in M2 TAMs and NSCLC cells effectively inhibited tumor growth and the stimulus-responsive drug release reduced the toxic side effects of the drug. The combination of doxycycline (anti-CAPN2) and docetaxel (anticancer drug) showed a synergistic inhibitory effect on tumor growth by suppressing CAPN2 expression.