Nanoparticle-Drug Systems against Cancer

 

Chemie  |  Biochemie  |  Medizin

 

Lukas Gurzeler, 2005 | Münchenbuchsee, BE

 

Photodynamic therapy (PDT) is a promising approach to cancer treatment that relies on a photosensitizer (PS), light energy, and oxygen to generate cytotoxic reactive oxygen species. While porphyrins are effective PSs, their incorporation into cancer cells remains a challenge due to poor solubility and aggregation tendencies. This study compares the encapsulation efficiency of mono-TCPP and tetra-TCPP in various nanocarriers, including liposomes, bicelles, Kolliphor RH40, beta-cyclodextrin, PVP, and PEG-PPG-PEG triblock copolymers. Encapsulation was performed using lipid hydration and simple dissolve techniques and analysed via 1H-NMR and 1H-1H NOESY spectroscopy. The findings show 87.5% encapsulation success for tetra-TCPP and 50% for mono-TCPP, suggesting that tetra-TCPP is more compatible with nanoparticle carriers.

Introduction

The primary purpose of the study is to answer the question of how the substitution pattern of porphyrins influence the encapsulation in nanoparticles utilizing the symmetry and polarity differences of the used porphyrins.

Methods

Liposomes and bicelles were prepared using lipid hydration techniques, with modifications for bicelles due to their distinct morphology. Polymeric nanocarriers and PEG-40 micelles were produced using a simple dissolve technique. Porphyrins were first characterized via UV-VIS spectroscopy and 1H-NMR to determine their absorption and emission spectra. The carrier systems were then analysed using 1H-NMR and 1H-1H NOESY spectroscopy, with data processed using TopSpin.

Results

Both porphyrins were encapsulated in bicelles, PEG-40 micelles, and Synperonic F108. Encapsulation was confirmed by 1H-NMR, where distinct porphyrin peaks appeared in nanocarrier spectra, and visually by changes in turbidity, which indicate particle formation. 1H-1H NOESY spectroscopy was used to determine porphyrin location, e.g., revealing that tetra-TCPP was distributed throughout the PEG-40 micelle layers, whereas mono-TCPP was limited to the inner and outer layers.

Discussion

The mono-substituted and tetra-substituted porphyrins show specific encapsulation preferences throughout the tested nanoparticles. These preferences can be assigned to the varying substitution pattern of the two porphyrins. The mono-substituted porphyrin demonstrated successful encapsulation in liposomes, bicelles, PEG-40 micelles, and Synperonic F108. The hydrophobic characteristic of mono-TCPP enables the encapsulation in the non-polar regions of the nanocarriers. In particular, the encapsulation in liposomes was exclusive to the mono-TCPP. The hydrophobicity of the mono-TCPP increased the aggregation rate in aqueous media, and thus, hindering the encapsulation process. This can be seen in the encapsulation results as well as the nanoparticle-systems in vitro. Contrary to the mono-TCPP, the tetra-TCPP showed broader encapsulation capacity, being encapsulated in all tested nanocarriers except liposomes. That results in an encapsulation success rate significantly higher than the success rate of mono-TCPP. The proven versatility can be assigned to its increased polarity and hydrophilicity which accompany the substituent pattern. The lower aggregation rate of tetra-TCPP was highly in favour of the encapsulation process and the large size of tetra-TCPP seemed not to hinder the encapsulation in nanoparticles.

Conclusions

This study highlights that porphyrins with more polar substituents have an advantage in nanoparticle encapsulation. The tested nanocarriers, which varied in size, polarity, and morphology, provided a useful model for studying these interactions. The observed encapsulation trends exceeded initial expectations, revealing clear preferences based on porphyrin polarity. Since many drugs are hydrophobic and struggle with poor solubility, this research underscores the importance of hydrophilic
drug design for nanocarrier-based delivery. NMR proved highly effective in tracking encapsulation, with 1H-1H NOESY particularly useful for localizing porphyrins within nanocarriers. Future research should focus on testing system stability through alternative analytical methods and exploring the photophysical properties and in vivo performance of encapsulated porphyrins.

 

 

Würdigung durch den Experten

Dr. Rolf Schütz

Lukas Gurzelers Arbeit zeugt von Engagement, Fachkompetenz und Sorgfalt. Er untersucht den Einbau zweier Photosensitizers unterschiedlicher Polarität in verschiedene Nanocarriers für die Photodynamische Therapie (PDT) und gewinnt praxisrelevante Erkenntnisse. Seine fundierte Recherche, analytische Herangehensweise, hohe Motivation und sein tiefes Verständnis der Thematik wissen zu überzeugen. Die Arbeit besticht durch ein hohes sprachliches Niveau und sorgfältige Darstellung. Besonders hervorzuheben ist, dass die gewonnenen Erkenntnisse und Methoden unmittelbare Anwendung in der Forschungsgruppe finden.

Prädikat:

hervorragend

Sonderpreis «European Union Contest for Young Scientists (EUCYS)» gestiftet von der Stiftung Aldo e Cele Daccò

 

 

 

Gymnasium Kirchenfeld, Bern
Berufsbildnerin: Dr. Martina Vermathen