4.6 Article

Targeting circulating monocytes with CCL2-loaded liposomes armed with an oncolytic adenovirus

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Publisher

ELSEVIER
DOI: 10.1016/j.nano.2021.102506

Keywords

Oncolytic virus; Adenovirus; Liposomes; Monocytes; Chemokine receptor 2; Prostate cancer

Funding

  1. European Commission [872860]
  2. European Union's Horizon 2020 research 517 and innovation programme under the Marie-Curie grant [C25574/A24321]
  3. Cancer Research UK (CRUK ) [675743]

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This study demonstrates that encapsulating oncolytic adenovirus into CCL2-coated liposomes can effectively target tumors by recruiting circulating monocytes expressing CCR2. The nanomedicine approach significantly reduces tumor size and metastasis, providing a potential strategy for treating inaccessible tumors.
Oncolytic viruses (OVs) selectively replicate in and destroy cancer cells resulting in anti-tumor immunity. However, clinical use remains a challenge because of virus clearance upon intravenous delivery. OV packaging using a nanomedicine approach could overcome this. Here we encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes in order to exploit recruitment of CCR2-expressing circulating monocytes into tumors. We demonstrate successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes that were preferentially taken up by CCR2-expressing monocytes. No complex-related toxicities were observed following incubation with prostate tumor cells and the encapsulation did not affect virus oncolytic activity in vitro. Furthermore, intravenous administration of our nanomedicine resulted in a significant reduction in tumor size and pulmonary metastasis in prostate cancer-bearing mice whereby a 1000-fold less virus was needed compared to Ad[I/PPT-E1A] alone. Taken together our data provide an opportunity to target OVs via circulation to inaccessible tumors using liposome-assisted drug delivery. (c) 2021 Elsevier Inc. All rights reserved.

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