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J Control Release. 2019 May 10;301:42-53. doi: 10.1016/j.jconrel.2019.03.009. Epub 2019 Mar 11.

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

Author information

1
Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA; Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
2
Department of Nanoengineering, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
4
Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
5
Department of Nanoengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
6
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
7
Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA; Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: pang0051@umn.edu.

Abstract

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.

KEYWORDS:

Cargo delivery; RXR beta targeting; Tumor homing; Tumor-associated macrophages

PMID:
30871996
PMCID:
PMC6500479
[Available on 2020-05-10]
DOI:
10.1016/j.jconrel.2019.03.009

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