The Nanomedicine and Nanotoxicology Group (GNano) at the São Carlos Physics Institute of the University of São Paulo (IFSC-USP) in Brazil has discovered a way to convert the bioceramic material hydroxyapatite into nanoparticles with enhanced intrinsic luminescence. This paves the way for the use of biocompatible and low-cost nanomaterials in biomedical imaging techniques.
“We have demonstrated that incorporating carbonate groups into the hydroxyapatite structure increases the concentration of crystal defects, which is responsible for increasing the material’s intrinsic luminescence. After functionalization with citrate, which improves colloidal stability in aqueous media, these calcium phosphate nanoparticles can be used as a luminescent agent for cellular bioimaging,” said Thales Rafael Machado, one of the study participants and FAPESP scholarship recipient. The recipient explained to Agêcia FAPESP.
The research was coordinated by Professor Valtencir Zucolotto of IFSC-USP and carried out in collaboration with the Center for Advanced Materials and Molecular Engineering (CEMol), a FAPESP Research, Innovation and Dissemination Center (RIDC) headquartered at the Brazilian Center for Energy and Materials Research (CNPEM) in Campinas.
Machado said the discovery was achieved by controlling the concentration of structural defects and point defects in the hydroxyapatite nanoparticles by incorporating varying levels of carbonate during synthesis. Samples with the highest carbonate content showed the most intense luminescence.
“Bioimaging capabilities were demonstrated by visualizing the internalization of the nanoparticles into cells using confocal fluorescence microscopy and relying solely on the intrinsic luminescence of the nanoparticles. Cellular internalization was also confirmed by flow cytometry based on the luminescence signal of the particles, while biocompatibility was assessed by a cytotoxicity assay,” said Machado.
According to Machado, the study of the defect chemistry and intrinsic luminescence of carbonated hydroxyapatite will contribute to the development of new hydroxyapatite-based photocatalytic materials for environmental applications. It also provides a basis for spectroscopic studies of hard tissues such as bones and teeth. “This knowledge can also be applied to the production of luminescent scaffolds for tissue engineering,” he added.
The study was published in the journal ACS Nanoscience Au From the American Chemical Society.
cancer treatment
In parallel research, GNano and CEMol developed an efficient and robust strategy to deliver gemcitabine, a widely used chemotherapy drug against cancers such as pancreatic cancer, via calcium phosphate nanoparticles.
“The system is designed to be dual pH-responsive, keeping the drug inactive under normal physiological conditions, such as in the bloodstream, and releasing the drug in its active form only in the more acidic environment characteristic of tumor areas. This increases bioavailability and therapeutic potential,” Machado says.
This research ACS Applied Biomaterialsalso from the American Chemical Society.
Additionally, the group demonstrated that the surface of nanoparticles could be functionalized with folic acid via a highly stable covalent bond. Folic acid acts as a targeting molecule because many tumor cells require more of this vitamin.
“Thus, this system combines controlled release and active targeting, which may facilitate increased drug concentrations in tested tumor cells, such as breast and cervical cancer, and reduce undesirable side effects in healthy tissues,” the USP San Carlos researchers explain.
This discovery began with the development of a prodrug of gemcitabine conjugated to a biocompatible polymer called carboxymethylcellulose. In this form, the drug is better protected from premature degradation in the body, is released only in acidic environments such as tumors and certain cell vesicles, and remains stable in the bloodstream. The same polymer was also used to stabilize calcium phosphate nanoparticles in suspension and prevent agglomeration.
Professor Machado emphasizes that these discoveries will contribute to the development of safer and more effective cancer treatments. “By keeping the drug inactive while it circulates through the body and releasing it preferentially into the tumor environment, this system has the potential to reduce side effects and enhance the direct action of the drug on tumor cells.”
The strategy is made safer by using nanoparticles made of calcium phosphate, a biocompatible material that occurs naturally in the human body. The combination of controlled release, response to tumor pH, and active targeting with folic acid represents an advance in nanomedicine and more precise treatments.
“Such a system could increase the efficiency of chemotherapy at lower doses, reduce damage to healthy tissue, and improve the quality of life of patients during treatment,” the researchers said.
GNano has developed a series of new nanostructured materials for advanced cancer diagnosis and treatment, and safer delivery systems for agricultural pesticides and biological inputs.
sauce:
São Paulo Research Foundation (FAPESP)
Reference magazines:
DOI: 10.1021/acsnanoscienceau.5c00140
