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PTX-RPPR, a conjugate of paclitaxel and NRP-1 peptide inhibitor to prevent tumor growth and metastasis. | LitMetric

PTX-RPPR, a conjugate of paclitaxel and NRP-1 peptide inhibitor to prevent tumor growth and metastasis.

Biomed Pharmacother

Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules, Department of Biomaterials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100026, China. Electronic address:

Published: September 2024

AI Article Synopsis

Article Abstract

Paclitaxel, a potent anti-tumor drug widely recognized for its therapeutic efficacy, has faced limitations in clinical application due to its poor solubility. The use of Cremophor EL (CrEL) as a cosolvent in paclitaxel injections has been associated with hypersensitivity reactions in some patients. To overcome these challenges, we have developed a novel conjugate by linking a neuropilin-1 targeting peptide, RPPR, to paclitaxel, resulting in PTX-RPPR. This innovative approach has significantly enhanced the solubility of paclitaxel, achieving a 3.8 mg/mL concentration, a remarkable 90-fold increase over the native drug. PTX-RPPR has shown potent anti-tumor activity, inhibiting tumor cell proliferation with an IC ranging from 0.26 to 1.64 μM and effectively suppressing migration, invasion, and angiogenesis at a concentration of 75 nM. Notably, in a 4T1 mammary carcinoma model, PTX-RPPR administered at a dose of 0.7 μmol/kg exhibited tumor growth inhibition comparable to that of paclitaxel at a higher dose of 3.5 μmol/kg, with superior efficacy in preventing lung metastasis. Furthermore, PTX-RPPR effectively reduced NRP-1 expression in both tumors and lungs post-treatment. In contrast to paclitaxel formulated with CrEL, PTX-RPPR did not induce IL-6 expression, suggesting a safer profile in terms of immunological response. Characterized by a particle size of 200 nm and a zeta potential of +30 mV, the nano-formulation of PTX-RPPR demonstrated remarkable stability over seven days. This study introduced PTX-RPPR as a promising peptide-drug conjugate that addresses the solubility and hypersensitivity issues associated with paclitaxel, offering a safer therapeutic strategy for cancer treatment.

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Source
http://dx.doi.org/10.1016/j.biopha.2024.117264DOI Listing

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