Calcium Phosphate Nanocomposite Particles for In Vitro Imaging and Encapsulated Chemotherapeutic Drug Delivery to Cancer Cells

Abstract

Paradigm-shifting modalities to more efficiently deliver drugs to cancerous lesions require the following attributes: nanoscale-size, targetability and stability under physiological conditions. Often, these nanoscale drug delivery vehicles are limited due to agglomeration, poor solubility or cytotoxicity. Thus, we have designed a methodology to encapsulate hydrophobic antineoplastic chemotherapeutics within a 20-30 nm diameter, pH-responsive, non-agglomerating, non-toxic calcium phosphate nanoparticle matrix. In the present study, we report on calcium phosphate nanocomposite particles (CPNP) that encapsulate both fluorophores and chemotherapeutics, are colloidally stable in physiological solution for extended time at 37°C and can efficaciously deliver hydrophobic antineoplastic agents, such as ceramide, in several cell model systems.

Functionalized Calcium Phosphate Nanoparticles for Biomedical Application

“…Cheng et al synthesized cisplatin-conjugated nanoparticles for chemotherapy [39] and Ramachadran et al performed the synthesis of insulin-functionalized particles for oral insulin delivery [39,40]. Kester et al produced stable calcium phosphate nanoparticles functionalized with the anticancer drug ceramide [41]. The further functionalization with PEG resulted in stable particles with a positive surface charge which should be easily taken up by cells [41].…”

“…Kester et al produced stable calcium phosphate nanoparticles functionalized with the anticancer drug ceramide [41]. The further functionalization with PEG resulted in stable particles with a positive surface charge which should be easily taken up by cells [41].…”

Evolving application of biomimetic nanostructured hydroxyapatite

“…The nanoparticles can be made to fluoresce by the incorporation of lanthanide ions, 161,162 and they can also act as carriers for different drugs, eg, insulin, 163 cisplatin, 164 or ceramide. 165 Liu et al have shown by in vivo experiments that calcium phosphate nanoparticles, carrying a suicide gene, can treat nasopharyngeal carcinoma. 166 The adsorption and release of bioactive molecules are strongly affected not only by the chemical properties of the drug molecule, but also by the chemical and structural characteristics of the HA substrates.…”

Fabrication of inorganic hydroxyapatite nanoparticles and organic biomolecules-dual encapsulated alginate microspheres

“…29 Kester et al utilized HA nanoparticles as a carrier to load chemotherapeutic drugs and fluorophores for chemotherapy and bioimaging at the same time. 30 They claimed that HA-based nanocarriers with a suitable particle size (30 nm) would exhibit pHresponse release properties, nonagglomeration, and low toxicity for drug delivery systems. Huang et al synthesized gold coated HAP@alginate as antibacterial material.…”