Tumor-specific macrophage targeting through recognition of retinoid X receptor beta

JOURNAL OF CONTROLLED RELEASE

卷:301

Article

Tang, Tang^1,2  Wei, Yushuang^1,2  Kang, Jinyoung³  She, Zhi-Gang⁴  Kim, Dokyoung⁵  Sailor, Michael J.^3,6  Ruoslahti, Erkki²  Pang, Hong-Bo^1,2 

[1] Univ Minnesota, Dept Pharmaceut, 2301 6th St SE, Minneapolis, MN 55455 USA

[2] Sanford Burnham Prebys Med Discovery Inst, Ctr Canc, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA

[4] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan, Hubei, Peoples R China

[5] Kyung Hee Univ, Coll Med, Dept Anat & Neurobiol, Seoul 02447, South Korea

[6] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

关键词: Tumor-associated macrophages;    Tumor homing;    RXR beta targeting;    Cargo delivery;   

DOI  :  10.1016/j.jconrel.2019.03.009

来源: Elsevier

【 摘 要 】

Macrophages play important and diverse roles during cancer progression. However, cancer therapies based on macrophage modulation are lacking in tools that can recognize and deliver therapeutic payloads to macrophages in a tumor-specific manner. As a result, treatments tend to interfere with normal macrophage functions in healthy organs. We previously identified a macrophage-binding peptide, termed CRV. Here, we show that upon systemic administration into tumor-bearing mice, CRV selectively homes to tumors, extravasates, and preferentially binds to macrophages within. CRV exhibits a higher affinity for tumor macrophages than for other cells in tumors or for other macrophage types elsewhere in the body. We further identified and validated retinoid X receptor beta (RXRB) as the CRV receptor. Intriguingly, although it is known as a nuclear receptor, RXRB shows a prominent cell surface localization that is largely restricted to tumor macrophages. Systemic administration of anti-RXRB antibodies also results in tumor-selective binding to macrophages similar to CRV. Lastly, we demonstrate the ability of CRV to improve the delivery of nano-carriers into solid tumors and macrophages within. In summary, we describe here a novel cell surface marker and targeting tools for tumor macrophages that may aid in future development of macrophage-modulatory cancer therapies.

【 授权许可】

Free