Substantial amount of research has been done in recent decades for the development of nanoparticle systems to selectively deliver drugs to cancer cells for concurrently enhancing and reducing anti-cancer and off-target effects, respectively. pH-sensitive carbonate apatite (CA) was originally developed for efficient and targeted delivery of DNA, siRNA and proteins to various cancer cell lines. Recently, the CA particles were employed to deliver anti-cancer drugs, cyclophosphamide, doxorubicin and methotrexate to cancer cells. Here, we report on the fabrication and characterization of gemcitabine- loaded CA particles, followed by the evaluation of their roles in enhancement of cytotoxicity in two human and one murine breast cancer cell lines. HPLC was performed to measure binding efficiency of the drug to the apatite particles whereas particle size and zeta potential were evaluated to characterize drug/apatite complex. Depending on the initial doses of the drug, its bind binding affinity towards the particles varied from 3.85% to 4.45%. The particle size was found to surprisingly decrease with an increase of the initial drug concentration. In vitro chemosensitivity assay revealed that apatite/drug nanoparticle complexes presented significantly higher cytotoxicity to breast cancer cells compared to free drugs, which could be correlated with the enhanced cellular uptake of the small size drug-loaded particles through endocytosis compared to the passive diffusion of the free drug.
PEG-functionalized nanoparticles as carriers of chemotherapeutics agents have been explored with notable successes in preclinical and clinical stages of cancer treatment, with some already approved by FDA, namely PEGylated liposomes and polymers. Half-life extension of therapeutic agents through PEGylation process improves their pharmacokinetic (PK) profiles, thereby reducing their dosing frequency. Protein corona composition of PEGylated nanoparticles (NPs) confers a tremendous influence on their surface characteristics which directly impact tumor accumulation and clearance properties of the drugs. By controlling the size and complexity of PEG molecules, as well as by attaching targeting moieties, the surface characteristics of NPs can be manipulated to improve their tumor uptake without sacrificing the circulation time. This review focuses on design and applications of PEGylated NPs for tumor targeted drug delivery in animal models and clinical setting.
Inorganic nanoparticles are commonly employed as vectors for delivering drugs into cancer cells while decreasing undesired cytotoxicity in healthy tissues. Carbonate apatite is an attractive nonviral vector that releases drugs at acidic environment inside the cells following endocytosis. However, maintaining the smaller particle size is crucial for enhancing cellular uptake of drugs as well as prolonging their systemic circulation time. We aimed to modify carbonate apatite with citrate for reducing the growth kinetics of carbonate apatite particles and enhancing the cellular uptake of cyclophosphamide via endocytosis. Several concentrations of sodium citrate were used to fabricate citrate-modified carbonate apatite (CMCA) particle complexes in absence or presence of cyclophosphamide. The binding affinity of the drug towards the particles and its cellular uptake were measured by high-performance liquid chromatography (HPLC). The nanoparticles' average size and zeta potential were determined by Malvern Zetasizer. Fourier-transform infrared spectroscopy (FTIR) was performed to justify association of citrate with carbonate apatite. MTT assay was performed to evaluate the cell viability. CMCA exhibited 6% more binding efficiency for cyclophosphamide and promoted fast cellular uptake of cyclophosphamide with enhanced cytotoxicity in MCF-7 cells, compared to unmodified carbonate apatite. Therefore, CMCA nanoparticles have a high potential for intracellular delivery of anti-cancer drugs and demand for further investigated in animal models of cancer.