Harnessing CD47 mimicry to inhibit phagocytic clearance and enhance anti-tumor efficacy of nanoliposomal doxorubicin

ABSTRACT

Background

We hypothesized if phagocytosis of liposomes by macrophages could be mitigated through incorporation of a CD47 mimicry peptide (Self peptide: SP) on the surface of liposomes.

Methods

Thin film hydration method followed by extrusion was used to prepare nanoliposomes, and Dox encapsulation in liposomes was done via remote-loading method. Decorated liposomes with SP peptide (SP-LD) at different peptide densities (300 and 600 peptides on the surface of each liposome) were prepared using a pre-insertion technique. Macrophage cell lines were used to compare the cellular uptake of decorated and unmodified liposomes. For biodistribution studies, tumor-bearing mice received the preparations, and fluorescence signals of Dox in different tissues were measured. To evaluate anti-tumor efficacy, tumor size and survival rates were assessed. Also, pharmacokinetic parameters were determined.

Results

Compared with PEGylated liposomes, uptake by macrophages was largely decreased when SP was incorporated on liposomes. Following intravenous injection, SP-liposomes were cleared more slowly compared with PEGylated liposomes. Eventually, SP-liposomes were highly distributed to tumor tissues compared with PEGylated liposomes, and significantly reduced tumor size and improved the survival of tumor-bearing mice.

Conclusions

This research showed reduced macrophage uptake, increased blood circulation, and enhanced tumor accumulation of liposomes through SP incorporation on the surface of particles.

KEYWORDS:

• Nanoliposome
• drug delivery
• CD47
• macrophage
• phagocytosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This project was financially supported by the Mashhad University of Medical Sciences Research Council (Mashhad, Iran). The project was also supported by a grant from cancer research center of cancer institute of Iran (Sohrabi cancer charity, Grant No: 37652-202-01-97) and a Grant No. 961204 of the Biotechnology Development Council of the Islamic Republic of Iran.