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

Tang Tang, Yushuang Wei, Jinyoung Kang, Zhi Gang She, Dokyoung Kim, Michael J. Sailor, Erkki Ruoslahti, Hong Bo Pang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)42-53
Number of pages12
JournalJournal of Controlled Release
Volume301
DOIs
StatePublished - May 10 2019

Bibliographical note

Funding Information:
This work was supported by grants from the National Cancer Institute ( R01CA214550 and R01CA188883 ) and the National Institutes of Biomedical Imaging and Bioengineering ( R21EB022652 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keywords

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

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