Biomacromolecules 2022, 23, 100-111.

Cetuximab-Polymersome-Mertansine Nanodrug for Potent and Targeted Therapy of EGFR-Positive Cancers

Targeted nanomedicines particularly armed with monoclonal antibodies are considered to be the most promising advanced chemotherapy for malignant cancers; however, their development is hindered by their instability and drug leakage problems. Herein, we constructed a robust cetuximabpolymersomemertansine nanodrug (C-P-DM1) for highly potent and targeted therapy of epidermal growth factor receptor (EGFR)-positive solid tumors. C-P-DM1 with a tailored cetuximab surface density of 2 per P-DM1 exhibited a size of ca. 60 nm, high stability with minimum DM1 leakage, glutathione-triggered release of native DM1, and 6.011.3-fold stronger cytotoxicity in EGFR-positive human breast (MDA-MB-231), lung (A549), and liver (SMMC-7721) cancer cells (IC50 = 27.1135.5 nM) than P-DM1 control. Notably, intravenous injection of C-P-DM1 effectively repressed subcutaneous MDA-MB-231 breast cancer and orthotopic A549-Luc lung carcinoma in mice without inducing toxic effects. Strikingly, intratumoral injection of C-P-DM1 completely cured 60% of mice bearing breast tumor without recurrence. This robust cetuximabpolymersomemertansine nanodrug provides a promising new strategy for targeted treatment of EGFR-positive solid malignancies.

S.J. Yue, Y.F. Zhang, Y.H. Wei, R. Haag, H.L. Sun*, and Z.Y. Zhong*, Cetuximab-Polymersome-Mertansine Nanodrug for Potent and Targeted Therapy of EGFR-Positive Cancers, Biomacromolecules 2022, 23, 100-111.