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Updated: Jan 26, 2026
Targeting Drugs to Larval Zebrafish Macrophages by Injecting Drug-Loaded Liposomes
Published on: February 18, 2020
Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response
Mesha Saeed1, Sara Zalba1, Ann L B Seynhaeve1
1Laboratory of Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC, Rotterdam, The Netherlands, t.l.m.tenhagen@erasmusmc.nl.
Purpose:
Melanoma is the most aggressive form of skin cancer. Chemotherapy at a late stage fails due to low accumulation in tumors, indicating the need for targeted therapy.
Materials And Methods:
To increase drug uptake by tumor cells, we have targeted doxorubicin-containing liposomes using a T-cell receptor (TCR)-like antibody (scFv G8 and Hyb3) directed against melanoma antigen A1 (MAGE-A1) presented by human leukocyte antigen A1 (M1/A1). With the use of flow cytometry and confocal microscopy, we have tested our formulation in vitro. In vivo pharmacokinetics was done in tumor-free nu/nu mice, while biodistribution and efficacy study was done in nu/nu mice xenograft.
Results:
We demonstrated two to five times higher binding and internalization of these immunoliposomes by M1+/A1+ melanoma cells in vitro in comparison with nontargeted liposomes. Cytotoxicity assay showed significant tumor cell kill at 10 µM doxorubicin (DXR) for targeted vs nontargeted liposomes. In vivo pharmacokinetics of nontargeted and targeted liposomes were similar, while accumulation of targeted liposomes was 2- to 2.5-fold and 6.6-fold enhanced when compared with nontargeted liposomes and free drug, respectively. Notably, we showed a superior antitumor activity of MAGE-A1-targeted DXR liposomes toward M1+/A1+ expressing tumors in mice compared with the treatment of M1-/A1+ tumors. Our results indicate that targeted liposomes showed better cytotoxicity in vitro and pharmacokinetics in vivo.
Conclusion:
Liposomes decorated with TCR-mimicking scFv antibodies effectively and selectively target antigen-positive melanoma. We showed that DXR-loaded liposomes coupled to anti-M1/-A1 scFv inflict a significant antitumor response. Targeting tumor cells specifically promotes internalization of drug-containing nanoparticles and may improve drug delivery and ultimately antitumor efficacy. Our data argue that targeting MAGE in A1 context, by nanosized carriers decorated with TCR-like antibodies mimicking scFv, can be used as a theragnostic platform for drug delivery, immunotherapy, and potentially imaging, and diagnosis of melanoma.
Insights
Targeted liposomes carrying doxorubicin effectively kill melanoma cells by selectively binding to MAGE-A1. This targeted approach enhances drug delivery and antitumor efficacy for aggressive skin cancer treatment.
Area of Science:
- Oncology
- Nanotechnology
- Immunology
Background:
- Melanoma is an aggressive skin cancer with limited treatment options.
- Conventional chemotherapy faces challenges due to poor drug accumulation in tumors.
- Targeted therapy is crucial for improving treatment outcomes in advanced melanoma.
Purpose of the Study:
- To develop and evaluate doxorubicin-loaded liposomes targeted to melanoma cells.
- To enhance drug uptake and efficacy using T-cell receptor (TCR)-like antibodies against melanoma antigen A1 (MAGE-A1).
Main Methods:
- Liposomes were engineered with TCR-mimicking single-chain variable fragment (scFv) antibodies targeting MAGE-A1.
- In vitro studies utilized flow cytometry and confocal microscopy for binding and internalization assays.
- In vivo studies involved pharmacokinetics, biodistribution, and efficacy assessments in xenograft mouse models.
Main Results:
- Targeted immunoliposomes showed 2-5 times greater binding and internalization by MAGE-A1-positive melanoma cells compared to non-targeted liposomes.
- In vitro cytotoxicity assays demonstrated significant tumor cell kill with targeted doxorubicin liposomes.
- In vivo studies revealed enhanced accumulation (2-6.6 fold) of targeted liposomes and superior antitumor activity against MAGE-A1-expressing tumors.
Conclusions:
- Liposomes functionalized with TCR-mimicking scFv antibodies effectively target MAGE-A1-positive melanoma.
- Targeted delivery of doxorubicin via these immunoliposomes significantly improves antitumor response.
- This targeted nanocarrier platform holds potential for melanoma theranostics, including drug delivery, immunotherapy, and imaging.
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