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

被引：64

作者：

Park, Yong Il ^{[1
]}

Kwon, Seung-Hae ^{[2
]}

Lee, Gibok ^{[1
]}

Motoyama, Keiichi ^{[3
]}

Kim, Min Woo ^{[4
]}

Lin, Min ^{[5
]}

Niidome, Takuro ^{[6
]}

Choi, Jung Hoon ^{[7
,8
]}

Lee, Ruda ^{[4
]}

机构：

[1] Chonnam Natl Univ, Sch Chem Engn, Gwangju 61186, South Korea

[2] Korea Basic Sci Inst, Seoul 02841, South Korea

[3] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan

[4] Kumamoto Univ, Int Res Org Adv Sci & Technol IROAST, Kumamoto 8608555, Japan

[5] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Minist Educ, Xian 710049, Peoples R China

[6] Kumamoto Univ, Fac Adv Sci & Technol, Kumamoto 8608555, Japan

[7] Kangwon Natl Univ, Dept Anat, Coll Vet Med, Chunchon 24341, South Korea

[8] Kangwon Natl Univ, Inst Vet Sci, Coll Vet Med, Chunchon 24341, South Korea

来源：

JOURNAL OF CONTROLLED RELEASE | 2021年 / 330卷

基金：

新加坡国家研究基金会; 日本科学技术振兴机构;

关键词：

Non-small cell lung cancer; pH-sensitive; Folate receptor beta; Calpain-2; Tumor microenvironment; PACLITAXEL; APOPTOSIS; THERAPY; NANOPARTICLES; THERAPEUTICS; CHEMOTHERAPY; DELIVERY;

D O I：

10.1016/j.jconrel.2020.12.011

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 (FR beta) 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, FR beta-targeted pH-sensitive liposomes were designed as carriers to ensure efficient drug delivery and acid-responsive release in NSCLC cells. Folate-mediated targeting of FR beta 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.

引用

页码：1 / 14

页数：14

共 37 条

[1] Principles of nanoparticle design for overcoming biological barriers to drug delivery [J].