ABSTRACT
Targeting tumors with nano-scale delivery systems shows promise to improve the therapeutic effects of chemotherapeutic drugs. However, the limited specificity of current nano-scale systems for cancer tissues prevents realization of their full clinical potential. Here, we demonstrate an effective approach to creating as targeted nanocarriers for drug delivery: MIONPs coated with integrin-targeted and matrix-metalloproteinase (MMP)-sensitive PEG hydrogel scaffolds. The functional PEG hydrogel coating has been designed for active loading as well as triggered intra-cellular release of the cancer therapeutic agent doxorubicin (DOX). Our study demonstrated that coated nanocarriers could be taken into cancer cells 11 times more efficiently than uncoated ones. Furthermore, confocal laser scanning microscopy images revealed that these targeted nanocarriers could efficiently deliver and release DOX into the nuclei of HeLa cells within 2h. Coating MIONPs with multifunctional PEG hydrogel could be a promising alternative to existing vehicles for targeted delivery of DOX into tumor tissue.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Drug Carriers , Ferric Compounds/chemistry , Matrix Metalloproteinases/chemistry , Metal Nanoparticles , Neoplasms/metabolism , Polyethylene Glycols/chemistry , HeLa Cells , Humans , Hydrogels , Magnetics , Microscopy, Electron, ScanningABSTRACT
Cysteine capped aqueous CdS quantum dots with improved luminescence and excellent colloidal-luminescence stability were developed in a simple one pot aqueous method from safer precursors at low temperatures. Investigation of size and luminescence as a function of cysteine amount, pH and temperature revealed an optimum value for all these variables to maximize the quantum yield. Cysteine:Cd ratio of 2, reaction pH of 9.5 and synthesis at room temperature-30 degrees C emerged as the best conditions for the highest QY of 19%. Yet, QY can be improved up to 55% if QDs are cleaned from excess cysteine and ions and redispersed in pH 7 medium. Size of the QDs, therefore the color of luminescence, can be tuned by the reaction temperature in this simple process. Higher temperatures provide larger particles. Cell uptake and cell viability studies in a wide range of doses and different incubation times with MCF-7 and HeLa cell lines revealed cell dependent differences. MCF-7 cells uptake more QDs but are much more viable than HeLa cells. At low doses such as 0.025 mg QD/ml all cells are viable. At 24 h incubation times MCF-7 cells demonstrate viability above 75% up to 0.15 mg QD/mI. On the other hand HeLa cells loose viability with increasing dose.
ABSTRACT
Highly stable and luminescent CdS quantum dots (QD) were prepared in aqueous solutions via in situ capping of the crystals with the poly(acrylic acid) (PAA) and mercaptoacetic acid (MAA) binary mixtures. The effect of reaction temperature and coating composition on the particle size, colloidal stability and luminescence were investigated and discussed in detail. CdS QDs coated with either PAA or MAA were also prepared and compared in terms of properties. CdS-MAA QDs were highly luminescent but increasing reaction temperature caused an increase in the crystal size and a significant decrease in the quantum yield (QY). Although less luminescent and bigger than CdS-MAA, CdS-PAA QDs maintained the room temperature size and QY at higher reaction temperatures. CdS-MAA QDs lacked long-term colloidal stability whereas CdS-PAA QDs showed excellent stability over a year. Use of PAA/MAA mixture as a coating for CdS nanoparticles during the synthesis provided excellent stability, high QY and ability to tune the size and the color of the emission. Combination of all of these properties can be achieved only with the mixed coating. CdS coated with PAA/MAA at 40/60 ratio displayed the highest QY (50% of Rhodamine B) among the other compositions.
