Virus-Like Particles Displaying Recombinant Short-Chain Fragment Region and Interleukin 2 for Targeting Colon Cancer Tumors and Attracting Macrophages

Abstract

Functionalized virus-like particles (VLPs) can target with specificity as drug delivery systems and can attract macrophages for the destruction of cancer cells. Here, the group antigen capsid protein from the Rous sarcoma virus was used to prepare VLPs, functionalized by displaying glycol-inositol phosphate-anchored recombinant single chain fragment variable (rscFv) and hemagglutinin transmembrane region anchored recombinant human interleukin-2 (rhIL2) (designated as VLP-rscFv-rhIL2s) in silkworms. The rscFv specifically binds the tumor-associated glycoprotein 72 that is expressed at the surface of colon cancer cells. VLP-rscFv-rhIL2 was affinity purified and had a smooth particle size with a diameter of 50 nm. Calcein-AM-packaged VLP-rscFv-rhIL2s successfully targeted cancer cells as a model for drug delivery system. VLP-rscFv-rhIL2 bound with colon cancer cells that attracted macrophages (human monocytic cell line-1 cells) in chemotaxis chamber assays compared with negative controls. The macrophages secreted tumor necrosis factor-α, a cytokine that is necessary to destroy cancer cells. These results demonstrate the potential of VLP-rscFv-rhIL2 as an intelligent nano biomaterial that is capable of attracting macrophages.

Phage-Based Applications in Synthetic Biology

“…The MS2 coat protein can tolerate insertions at several locations, allowing cargo to be introduced within the VLP. Modifications include tags to attach therapeutic payloads (drugs, enzymes, nucleic acids, homing peptides), moieties for targeting to specific animal tissues, and chemical functionalization for improved resilience against degradation (101)(102)(103)(104)(105)(106)(107)(108).…”

Protein-driven nanomedicines in oncotherapy

“…Johnson grass chlorotic stripe mosaic VLPs produced in tobacco cells have been recently loaded with antitumor doxorubicin [40], and targeted Rous sarcoma VLPs produced in Silkworm specifically delivered encapsulated doxorubicin in colon carcinoma cell lines [41]. In a more innovative approach, Rous sarcoma VLPs were double functionalized with a targeting and therapeutic moiety to specifically deliver Interleukin-2 (IL-2) to colon carcinoma cell lines and induce macrophage attraction [42].…”

Virus‐inspired and mimetic designs in non‐viral gene delivery

“…In vitro and in vivo assays highlighted the importance of AdGRGDS targeting specificity to tumor cells with integrin α v β 3 overexpression and demonstrated that the PEI‐CD/AdGRGDS gene delivery system had great potential for targeted tumor therapy. Furthermore, as a new type of bio‐planning tool, phage display technology was found to be a novel candidate with respect to identifying homing cell targeting/penetrating peptides for targeted drug or gene livery in recent years …”

“…Furthermore, as a new type of bioplanning tool, phage display technology was found to be a novel candidate with respect to identifying homing cell targeting/penetrating peptides for targeted drug or gene livery in recent years. 77,78…”