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.

• Authors: Seyed Mohammad Gheibi Hayat, Mahmoud R Jaafari, Mahdi Hatamipour, Tannaz Jamialahmadi, Amirhossein Sahebkar
• Journal: Expert opinion on drug delivery (Expert Opin Drug Deliv) Vol. 17 Issue 7 Pg. 1049-1058 (07 2020) ISSN: 1744-7593 [Electronic] England
• PMID: 32434390 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• CD47 Antigen
• CD47 protein, human
• Liposomes
• Peptides
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics)
• CD47 Antigen (metabolism)
• Cell Line, Tumor
• Doxorubicin (administration & dosage)
• Humans
• Liposomes
• Male
• Mice
• Mice, Inbred BALB C
• Peptides (metabolism)
• Polyethylene Glycols (chemistry)
• Tissue Distribution