Interaction of Folic Acid with Nanocrystalline Apatites and Extension to Methotrexate (Antifolate) in View of Anticancer Applications

Abstract

Nanocrystalline apatites mimicking bone mineral represent a versatile platform for biomedical applications thanks to their similarity to bone apatite and the possibility to (multi)functionalize them so as to provide "à la carte" properties. One relevant domain is in particular oncology, where drug-loaded biomaterials and engineered nanosystems may be used for diagnosis, therapy, or both. In a previous contribution, we investigated the adsorption of doxorubicin onto two nanocrystalline apatite substrates, denoted HA and FeHA (superparamagnetic apatite doped with iron ions), and explored these drug-loaded systems against tumor cells. To widen their applicability in the oncology field, here we examine the interaction between the same two substrates and two other molecules: folic acid (FA), often used as cell targeting agent, and the anticancer drug methotrexate (MTX), an antifolate analogue. In a first stage, we investigated the adsorptive behavior of FA (or MTX) on both substrates, evidencing their specificities. At low concentration, typically under 100 mmol/L, adsorption onto HA was best described using the Sips isotherm model, while the formation of a calcium folate secondary salt was evidenced at high concentration by Raman spectroscopy. Adsorption onto FeHA was instead fitted to the Langmuir model. A larger adsorptive affinity was found for the FeHA substrate compared to HA; accordingly, a faster release was noticed from HA. In vitro tests carried out on human osteosarcoma cell line (SAOS-2) allowed us to evaluate the potential of these compounds in oncology. Finally, in vivo (subcutaneous) implantations in the mouse were run to ascertain the biocompatibility of the two substrates. These results should allow a better understanding of the interactions between FA/MTX and bioinspired nanocrystalline apatites in view of applications in the field of cancer.

Advanced Materials Based on Nanosized Hydroxyapatite

“…Then the mist was pyrolyzed at 1000 °C to synthesize HAP–ferrite hybrid particles [ 152 ]. To conclude this section, we could not forget all the work that Anna Tampieri and her group have done on this subject, so we recommend to all those interested in this particular field to consult her proficient bibliography [ 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 ].…”

Bio-inspired apatite particles limit skin penetration of drugs for dermatology applications

“…Permeation study: Folic acid (FA) was used as a model drug, adsorbed on the surface of the (PEG)p-stabilized colloidal particles. The relevance of selecting FA as a model drug here relies in the easiness to titrate it by UV spectroscopy (at λ = 280 nm) and to the fact that adsorption of FA onto the surface of (non-colloidal) biomimetic apatites was recently proven to be effective [26]. The colloids were obtained from the reference protocol indicated earlier (part 2.1.…”

Mimicking bone–metal exchanges with synthetic nanocrystalline apatites

“…Carbonated nanocrystalline apatites (NCAs) have been proposed as a bone mineral surrogate for in vitro studies, including sorption of bis-phosphonates and nucleotides at physiological pH. [30][31][32] The direct adaptation to uranium(VI) of the proposed experimental set-up led to complete uranium(VI) sorption within few minutes, in total disagreement with the distribution of uranium in the body after contamination. 33,34 Based on this intriguing results, we embarked on a precise description of the chemical behavior of NCAs prepared according to the well established wet precipitation methods mentioned above.…”