Micro- and Nanoscale CaCO3 Carriers for Localized Melanoma Therapy: Impact of ‘Cold’ Labeling on Drug Loading, Release, and In Vivo Performance

Abstract

Calcium carbonate drug delivery system provides a very promising strategy for various types of treatment, including chemo-and radiotherapy. Effective design of this platform including surface engineering and employing organic/inorganic additives has significant influence on drug loading, stability and its release. In this paper, calcium carbonate microparticles (mCa) and nanoparticles (nCa) were synthesized for drug loading of novel therapeutic molecules and subjected to socalled 'cold' labeling procedure, i.e. efficient non-radioactive synthetic routes that can be applied to radionuclide labeling. In this context, the effect of 'cold' labeling conditions on morphology, size, drug loading, colloidal stability and drug release of mCa and nCa was fully assessed. The in vitro cytotoxicity, cellular uptake and hemolysis were examined on 'cold' mCa and nCa to reveal any impacts. Further, we have analyzed in vivo biodistribution of 'cold' mCa and 'cold' nCa and their estimated therapeutic efficiency after drug loading. The main characteristics of mCa and nCa were collected and compared to each other. It was shown that mCa and nCa can be effectively accumulated within the tumors in vivo without any release into healthy organs. Notably, 'cold' labeling procedure did not have an impact on therapeutic effect of drug loaded mCa and nCa. Due to this, the developed pharmaceutical forms of mCa and nCa have remarkable antitumor effects against melanoma showing tumor inhibition of ~76-84% without any significant side effects. This investigation can contribute to the development of calcium carbonate particles as a universal multifunctional delivery platform for effective tumor therapy and simultaneously accelerates clinical translation for various types of treatment.