TY - JOUR
T1 - Tumor-specific macrophage targeting through recognition of retinoid X receptor beta
AU - Tang, Tang
AU - Wei, Yushuang
AU - Kang, Jinyoung
AU - She, Zhi Gang
AU - Kim, Dokyoung
AU - Sailor, Michael J.
AU - Ruoslahti, Erkki
AU - Pang, Hong Bo
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/5/10
Y1 - 2019/5/10
N2 - 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.
AB - 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.
KW - Cargo delivery
KW - RXR beta targeting
KW - Tumor homing
KW - Tumor-associated macrophages
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U2 - 10.1016/j.jconrel.2019.03.009
DO - 10.1016/j.jconrel.2019.03.009
M3 - Article
C2 - 30871996
AN - SCOPUS:85063065878
SN - 0168-3659
VL - 301
SP - 42
EP - 53
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -