0604832 - ÚMCH 2026 RIV US eng J - Journal Article
Pytlíková, Sára - Konefal, Rafal - Pola, Robert - Braunová, Alena - Lobaz, Volodymyr - Šlouf, Miroslav - Beneš, Hynek - Starenko, Daniil - Běhalová, Kateřina - Kovář, Marek - Etrych, Tomáš - Laga, Richard - Pechar, Michal
Dual thermo- and pH-responsive polymer nanoparticle assemblies for potential stimuli-controlled drug delivery.
ACS Applied Bio Materials. Roč. 8, č. 1 (2025), s. 271-284. ISSN 2576-6422. E-ISSN 2576-6422
R&D Projects: GA MŠMT(CZ) LUAUS24239; GA MŠMT LX22NPO5102; GA MŠMT(CZ) LM2023053
Institutional support: RVO:61389013 ; RVO:61388971
Keywords : thermoresponsive polymers * pH-sensitive polymers * self-assembling block copolymers
OECD category: Polymer science; Pharmacology and pharmacy (MBU-M)
Impact factor: 4.7, year: 2023
Method of publishing: Open access
Result website:
https://pubs.acs.org/doi/10.1021/acsabm.4c01167DOI: https://doi.org/10.1021/acsabm.4c01167

The development of stimuli-responsive drug delivery systems enables targeted delivery and environment-controlled drug release, thereby minimizing off-target effects and systemic toxicity. We prepared and studied tailor-made dual-responsive systems (thermo- and pH-) based on synthetic diblock copolymers consisting of a fully hydrophilic block of poly[N-(1,3-dihydroxypropyl)methacrylamide] (poly(DHPMA)) and a thermoresponsive block of poly[N-(2,2-dimethyl-1,3-dioxan-5-yl)methacrylamide] (poly(DHPMA-acetal)) as drug delivery and smart stimuli-responsive materials. The copolymers were designed for eventual medical application to be fully soluble in aqueous solutions at 25 °C. However, they form well-defined nanoparticles with hydrodynamic diameters of 50–800 nm when heated above the transition temperature of 27–31 °C. This temperature range is carefully tailored to align with the human body’s physiological conditions. The formation of the nanoparticles and their subsequent decomposition was studied using dynamic light scattering (DLS), transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR). 1H NMR studies confirmed that after approximately 20 h of incubation at pH 5, which closely mimics tumor microenvironment, approximately 40% of the acetal groups were hydrolyzed, and the thermoresponsive behavior of the copolymers was lost. This smart polymer response led to disintegration of the supramolecular structures, possibly releasing the therapeutic cargo. By tuning the transition temperature to the values relevant for medical applications, we ensure precise and effective drug release. In addition, our systems did not exhibit any cytotoxicity against any of the three cell lines. Our findings underscore the immense potential of these nanoparticles as eventual advanced drug delivery systems, especially for cancer therapy.
Permanent Link: https://hdl.handle.net/11104/0362350