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Peer-reviewedCC BYNanoscale advances

Identification of B-cell maturation antigen (BCMA)-targeting peptides and selective drug delivery to multiple myeloma using peptide-targeted DM1 prodrug-loaded nanoparticles

  • Gyoyeon Hwang1,2,3
  • Raeleen H Sobetski1,2,3
  • Doga E Karakus4
  • Emily K Bromley1,2,3
  • Basar Bilgicer1,4,2,3
4 affiliations
  1. 1Department of Chemical and Biomolecular Engineering, University of Notre Dame Notre Dame IN USA [email protected].
  2. 2Mike and Josie Harper Cancer Research Institute, University of Notre Dame Notre Dame IN USA.
  3. 3Berthiaume Institute for Precision Health, University of Notre Dame Notre Dame IN USA.
  4. 4Department of Chemistry and Biochemistry, University of Notre Dame Notre Dame IN USA.
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Abstract

Selective delivery of anticancer therapeutics to tumor cells, without affecting healthy tissues, is crucial for effective cancer treatment. Recently, targeted therapies that exploit B-cell maturation antigen (BCMA), highly overexpressed on multiple myeloma (MM) cells, have emerged, demonstrating promising therapeutic efficacy. However, high-affinity ligands targeting BCMA may bind to low-level BCMA expression on normal cells, posing risks of off-target toxicity. To address this issue, we designed BCMA-targeting peptides (BCMApep) and identified BCMApep1 with a low affinity. BCMApep1 was multivalently conjugated on a liposomal nanoparticle surface (TNPBCMApep1), achieving selective and enhanced uptake by MM cells via the avidity effect. Furthermore, we loaded a mertansine (DM1) prodrug within the BCMA-targeted nanoparticles (TNPBCMApep1[DM1]), which demonstrated significantly superior cytotoxicity and apoptosis in MM cells upon pulse dosing compared to DM1 prodrug-loaded non-targeted nanoparticles (NP[DM1]). Overall, our study establishes a BCMA-targeting, peptide-guided nanoparticle platform for selective delivery of the DM1 prodrug to MM cells. The enhanced efficacy of TNPBCMApep1[DM1] highlights its potential as a safe and effective therapeutic strategy for multiple myeloma.

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Cite

BibTeXRIS
BibTeX
@article{hwang2026identification,
  title = {{Identification of B-cell maturation antigen (BCMA)-targeting peptides and selective drug delivery to multiple myeloma using peptide-targeted DM1 prodrug-loaded nanoparticles}},
  author = {Gyoyeon Hwang and Raeleen H Sobetski and Doga E Karakus and Emily K Bromley and Basar Bilgicer},
  journal = {Nanoscale advances},
  year = {2026},
  month = oct,
  doi = {10.1039/d6na00398b},
  url = {https://europepmc.org/article/PMC/PMC13726103},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Identification of B-cell maturation antigen (BCMA)-targeting peptides and selective drug delivery to multiple myeloma using peptide-targeted DM1 prodrug-loaded nanoparticles
AU  - Gyoyeon Hwang
AU  - Raeleen H Sobetski
AU  - Doga E Karakus
AU  - Emily K Bromley
AU  - Basar Bilgicer
PY  - 2026
DA  - 2026/10/09
JO  - Nanoscale advances
DO  - 10.1039/d6na00398b
UR  - https://europepmc.org/article/PMC/PMC13726103
AB  - Selective delivery of anticancer therapeutics to tumor cells, without affecting healthy tissues, is crucial for effective cancer treatment. Recently, targeted therapies that exploit B-cell maturation antigen (BCMA), highly overexpressed on multiple myeloma (MM) cells, have emerged, demonstrating promising therapeutic efficacy. However, high-affinity ligands targeting BCMA may bind to low-level BCMA expression on normal cells, posing risks of off-target toxicity. To address this issue, we designed BCMA-targeting peptides (BCMApep) and identified BCMApep1 with a low affinity. BCMApep1 was multivalently conjugated on a liposomal nanoparticle surface (TNPBCMApep1), achieving selective and enhanced uptake by MM cells via the avidity effect. Furthermore, we loaded a mertansine (DM1) prodrug within the BCMA-targeted nanoparticles (TNPBCMApep1[DM1]), which demonstrated significantly superior cytotoxicity and apoptosis in MM cells upon pulse dosing compared to DM1 prodrug-loaded non-targeted nanoparticles (NP[DM1]). Overall, our study establishes a BCMA-targeting, peptide-guided nanoparticle platform for selective delivery of the DM1 prodrug to MM cells. The enhanced efficacy of TNPBCMApep1[DM1] highlights its potential as a safe and effective therapeutic strategy for multiple myeloma.
SN  - 2516-0230
ER  -