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Preparation and Evaluation of Docetaxel-Loaded Targeted Poly (β‑amino Ester) - Magnetic Nanoparticles for
Nafiseh Sarkhosh1, Mohammad Reza Kandi2, Akram Mahna3
1Medical Physics Department, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Background:
Magnetodynamic therapy (MDT), which utilizes the mechanical motion of magnetic nanoparticles (MNPs) under low-frequency magnetic fields (LFMFs), has emerged as a promising approach to overcome the major limitations of traditional chemotherapy. This study aims to evaluate an integrated therapeutic strategy, termed chemo-MDT, under in vitro conditions.
Methods:
In this study, MNPs were modified with poly (β-amino ester) (PBAE) and functionalized with a CD44 aptamer for targeted delivery of docetaxel (DTX). The drug loading efficiency (LE) and drug loading capacity (LC) were determined. We investigated the effects of various LFMFs, specifically alternating magnetic fields (LFAMF), static magnetic fields (LFSMF), and their combination (LFSAMF), on the physicochemical properties, drug release, cellular uptake, and viability of 4T1 cancer cells.
Results:
The LE and LC of the engineered nanoparticles were found to be 91.92% and 8.35%, respectively. Aptamer-mediated targeting increased cellular uptake by 1.4-fold and enhanced magnetodynamic therapeutic efficiency by approximately two-fold compared to non-targeted nanoparticles. At the IC25 dose, DTX-loaded nanoparticles (NDTX) reduced cell viability to 71%, while the CD44 aptamer-functionalized ones (apt-NDTX) decreased it to 49.77%. Subsequent exposure to LFAMF led to a further reduction in viability to 36.75%. This improvement is primarily attributed to the intrinsic magnetodynamic effect arising from nanoparticle oscillation and the disruption of CD44-associated membrane protein complexes, rather than changes in drug release or uptake, both of which remained unaffected by LFAMF. Conversely, static magnetic fields produced negligible and, in some cases, slightly adverse effects on physicochemical or therapeutic properties; however, the combination of alternating and static fields mitigated these adverse effects.
Conclusion:
Collectively, these findings demonstrate that targeted delivery, when combined with magnetodynamic stimulation, forms an effective integrated chemo-MDT strategy that significantly enhances cancer cell killing through complementary targeting and mechanical mechanisms.
