EGF Receptor-Targeting Cancer Therapy Using CD47-Engineered Cell-Derived Nanoplatforms
Moon Jung Choi1, Kang Chan Choi1, Do Hyun Lee1
1Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
Introduction:
Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.
Methods:
The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.
Results:
The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.
Discussion:
These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.
Insights
Engineered nanoparticles expressing CD47 protein evade immune cells, while anti-EGFR antibodies target tumors. This dual-functionality enhances anti-cancer drug delivery and suppresses tumor growth effectively.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapeutics
Background:
- Clinical application of nanoparticle therapeutics is hindered by phagocytic cell uptake and off-target toxicity.
- Developing strategies to evade immune surveillance and improve tumor targeting is crucial for effective cancer treatment.
Purpose of the Study:
- To engineer CD47-expressing nanoparticles (CDNs) for enhanced anti-cancer drug delivery.
- To evaluate the efficacy of CDNs functionalized with anti-EGFR antibodies for targeted cancer therapy.
Main Methods:
- CDNs were prepared from CD47-transfected human embryonic kidney cells.
- Doxorubicin (DOX) was loaded into CDNs, and anti-EGFR antibodies were conjugated for targeted delivery.
- In vitro and in vivo studies were conducted to assess cellular uptake, tumor targeting, and anti-cancer efficacy.
Main Results:
- Synthesized CD47+iCDNs-DOX demonstrated stable structures and reduced uptake by macrophages.
- Targeted CDNs selectively recognized EGFR-positive cancer cells and accumulated in tumor xenografts.
- iCDNs-DOX significantly suppressed tumor growth in mice, indicating enhanced drug delivery.
Conclusions:
- Functionalizing cell membrane-derived nanocarriers with CD47 and tumor-targeting antibodies can overcome immune evasion and improve drug delivery.
- This approach shows promise for facilitating the clinical application of biocompatible nanocarriers in cancer therapy.
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