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Photosensitizer loaded calcium carbonate particles for theranostics

Name
Bogdan
Surname
Parakhonskiy
Scientific organization
Saratov State University
Academic degree
PhD
Position
senior reasercher
Scientific discipline
Life Sciences & Medicine
Topic
Photosensitizer loaded calcium carbonate particles for theranostics
Abstract
Calcium carbonate is an important inorganic biomaterial thanks to its chemical stability, bioactivity, and biocompatibility, which made it an interesting candidate for drug delivery systems. We report on studies of photosensitizer loaded vaterite containers in cell culture assays, and in vivo biodistribution. The resultant uptake of particles demonstrated particles accumulation in the tumour was benchmarked as 0.43 of that in the liver. Such pharmacokinetics of vaterite particles holds promise for its deployment in drug delivery applications
Keywords
vaterite, particles, drug delivery, photosensitizer, photodynamic therapy, porphyrazine, molecular rotors
Summary

Photosensitizer loaded calcium carbonate particles  for theranostics

B. Parakhonskiy1,2,3 , N.Yu Shilyagina4 I.V. Balalaeva4, L.G. Klapshina4,5, D.A. Gorin1,2, A.V. Zvyagin4,7* G. Sukhorukov1,6

1) Institute of Nanostructures and Biosystems, Saratov State University, 410012 Saratov, Russia

2) A.V. Shubnikov Institute of Crystallography, RAS, 119333, Moscow, Russia

3) Department of Molecular Biotechnology, Ghent University, Ghent, Belgium, 9000 Ghent, Belgium

4) Lobachevsky Nizhny Novgorod State University, 603950 Nizhny Novgorod, Russia

5) Institute of Organometallic Chemistry of the RAS, Nizhny Novgorod, Russia.

6) Queen Mary University of London, London, E1 4NS, United Kingdom.

7) ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW 2109, Australia

 

Calcium carbonate is an important inorganic biomaterial thanks to its chemical stability, bioactivity, and biocompatibility. These properties have recently made it an interesting candidate for drug delivery systems. Calcium carbonate exists in three anhydrous polymorphic modifications: vaterite, aragonite, and calcite. Under normal conditions, vaterite is an unstable phase, while calcite and aragonite are stable. Vaterite polycrystalline particles have further favorable properties like high porosity, large surface area, and negative zeta potential. We present a novel technique for the synthesis of CaCO3 containers. Porous polycrystalline particles were fabricated with controllable average sizes from 400 nm up to 10 microns. Several levels of control on these release dynamics could be identified: 1) The immersion medium: capsules immersed in water, showed a delayed burst release of the dye, coinciding with the crystal phase transition from vaterite to calcite. In ethanol this phase transition was inhibited, consequently only a slow desorption of the encapsulated dye was found. 2) Surface modification: Covering microcontainers with additional layers of biocompatible polyelectrolyte increases the payload release time.  3) pH value: A change of the pH from neutral to acid conditions will instead lead to a destruction of the vaterite matrix leading to an immediate release.

In current work we have demonstrated that vaterite particles were capable to load a substantial amount of anticancer photosensitizer drug porphyrazine. Porphyrazine is a molecular rotor whose fluorescence intensity and lifetime enabled fluorescence imaging and assessment of its rotation mobility in particles, cells and biological tissues.

In vitro and in vivo studies of the particles loading, cell uptake and particles bio distribution in organs were performed. After the one hour of incubation with the human breast adenocarcinoma cells the particles successfully penetrate through the cell membrane and predominantly localized in the cytoplasm.

For in vivo studies the loaded vaterite particles dispersed in buffer solution was injected intravenously in a wild-type mouse (Balb/c) bearing a grafted colorectal adenocarcinoma.  The resulted accumulation of vaterite particles in the tumor was 0.4 respect to the in the liver. That have been confirmed via two methods: fluorescence whole-animal imaging and histology analysis.  Such high tumor uptake efficiency possible explain via the enhanced permeability and retention.  Flexible loading and release control mechanisms, the perfect biocompatibility and revealed pharmacokinetic have proven the system’s potential for future pharmaceutical applications.