Abstract
Self-assembled prodrugs (SAPDs), which combine prodrug strategy and the merits of self-assembly, not only represent an appealing type of therapeutics, enabling the spontaneous organization of supramolecular nanocomposites with defined structures in aqueous environments, but also provide a new method to formulate existing drugs for more favorable outcomes. To increase drug loading and combination therapy, we covalently conjugated paclitaxel (PTX) and camptothecin (CPT) through a disulfide linker into a prodrug, designated PTX-S-S-CPT. The successful production of PTX-S-S-CPT prodrug was confirmed by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). This prodrug spontaneously undergoes precipitation in aqueous surroundings. Taking advantage of a flow-focusing microfluidics platform, the prodrug nanoparticles (NPs) have good monodispersity, with good reproducibility and high yield. The as-prepared prodrug NPs were characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM), demonstrating spherical morphology of around 200 nm in size. In the end, the self-assembled NPs were added to mouse embryonic fibroblast (MEF), mouse lung adenocarcinoma and Lewis lung carcinoma (LLC) cell lines, and human non-small cell lung cancer cell line A549 to evaluate cell viability and toxicity. Due to the redox response with a disulfide bond, the PTX-S-S-CPT prodrug NPs significantly inhibited cancer cell growth, but had no obvious toxicity to healthy cells. This prodrug strategy is promising for co-delivery of PTX and CPT for lung cancer treatment, with reduced side effects on healthy cells.
Original language | English |
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Article number | 1169 |
Journal | Pharmaceutics |
Volume | 12 |
Issue number | 12 |
DOIs | |
Publication status | Published - Dec 2020 |
MoE publication type | A1 Journal article-refereed |
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Åbo Akademi Functional Printing Center
Toivakka, M. (PI), Rosenholm, J. (PI), Anttu, N. (PI), Bobacka, J. (PI), Huynh, T. P. (PI), Peltonen, J. (PI), Wang, X. (PI), Wilen, C.-E. (PI), Xu, C. (PI), Zhang, H. (PI) & Österbacka, R. (PI)
Faculty of Science and EngineeringFacility/equipment: Facility