Diti Desai - Academia.edu (original) (raw)
Papers by Diti Desai
European Journal of Pharmaceutics and Biopharmaceutics, 2015
Cancerous cells have a rapid metabolism by which they take up sugars, such as glucose, at signifi... more Cancerous cells have a rapid metabolism by which they take up sugars, such as glucose, at significantly higher rates than normal cells. Celastrol is a traditional herbal medicine known for its anti-inflammatory and anti-cancer activities. The poor aqueous solubility and lack of target selectivity of celastrol, result in low therapeutic concentration of the drug reaching subcellular compartments of the target tissue, making it an interesting candidate for nanoparticulate delivery. The goal of this study was to utilize glucose as an affinity ligand decorated on mesoporous silica nanoparticles (MSNs), with the aim of delivering these celastrol-loaded MSNs with high specificity to cancer cells and inducing minimal off-target effects in healthy cells. MSNs were thus functionalized with sugar moieties by two different routes, either by conjugation directly to the MSN surface or mediated by a hyperbranched poly(ethylene imine), PEI layer; the latter to increase the cellular uptake by providing an overall positive surface charge as well as to increase the reaction sites for sugar conjugation. The effect of surface functionalization on the target-specific efficacy of the particles was performed by analyzing the uptake in HeLa and A549 cells as cancer cell models, as compared to mouse embryonic fibroblasts (MEF) as a representative for normal cells. To this end a comprehensive analysis strategy was employed, including flow cytometry, confocal microscopy, and spectrophotometry. When the apoptotic effect of celastrol was evaluated, the anti-cancer activity of celastrol was shown to be significantly enhanced when it was loaded into the specifically designed MSNs. The particles themselves did not induce any toxicity, and normal cells displayed minimal off-target effects. In summary, we show that glucose-functionalized MSNs can be used as highly efficient carriers for targeted celastrol delivery to achieve specific apoptosis in cancer cells.
Biomater. Sci., 2014
Aimed at utilizing high-magnetization nanospheres for magnetic field-enhanced cellular labeling, ... more Aimed at utilizing high-magnetization nanospheres for magnetic field-enhanced cellular labeling, coreshell structured sandwich-like magnetic mesoporous silica nanospheres were developed. While the magnetite cluster core can provide a high magnetic response for overcoming Brownian motion in cell culture media, the layered silica shell facilitates an efficient fluorescent dye labeling. However, the problem of particle aggregation in cell media, which is strongly enhanced under a magnetic field, significantly impeded the uptake by cells, resulting in difficulties in the precise analysis of the degree of particle internalization by fluorescence-based techniques (flow cytometry and confocal microscopy). To overcome this, reflection-based assessment was employed. Further, emphasis was put on utilizing the unique role of surface-hyperbranched polyethylenimine (PEI) in efficient prevention of particle aggregation prior to cell internalization in the presence of an external magnetic field. The interparticle attraction forces originating from magnetic dipole-dipole interactions are hereby balanced by the steric and electrostatic repulsion forces provided by the PEI functionalization, which leads to dispersed nanospheres in cell culture media during the magnetic-field induced cell labeling. As a consequence, PEI functionalization and the presence of the magnetic field synergistically enhanced the efficiency of MRI-fluorescence dual-mode labeling for cellular tracking.
Nanoscale Research Letters, 2012
In nanomedicine, physicochemical properties of the nanocarrier affect the nanoparticle's pharmaco... more In nanomedicine, physicochemical properties of the nanocarrier affect the nanoparticle's pharmacokinetics and biodistribution, which are also decisive for the passive targeting and nonspecific cellular uptake of nanoparticles. Size and surface charge are, consequently, two main determining factors in nanomedicine applications. Another important parameter which has received much less attention is the morphology (shape) of the nanocarrier. In order to investigate the morphology effect on the extent of cellular internalization, two similarly sized but differently shaped rod-like and spherical mesoporous silica nanoparticles were synthesized, characterized and functionalized to yield different surface charges. The uptake in two different cancer cell lines was investigated as a function of particle shape, coating (organic modification), surface charge and dose. According to the presented results, particle morphology is a decisive property regardless of both the different surface charges and doses tested, whereby rodlike particles internalized more efficiently in both cell lines. At lower doses whereby the shape-induced advantage is less dominant, charge-induced effects can, however, be used to fine-tune the cellular uptake as a prospective 'secondary' uptake regulator for tight dose control in nanoparticle-based drug formulations.
European Journal of Pharmaceutics and Biopharmaceutics, 2015
Cancerous cells have a rapid metabolism by which they take up sugars, such as glucose, at signifi... more Cancerous cells have a rapid metabolism by which they take up sugars, such as glucose, at significantly higher rates than normal cells. Celastrol is a traditional herbal medicine known for its anti-inflammatory and anti-cancer activities. The poor aqueous solubility and lack of target selectivity of celastrol, result in low therapeutic concentration of the drug reaching subcellular compartments of the target tissue, making it an interesting candidate for nanoparticulate delivery. The goal of this study was to utilize glucose as an affinity ligand decorated on mesoporous silica nanoparticles (MSNs), with the aim of delivering these celastrol-loaded MSNs with high specificity to cancer cells and inducing minimal off-target effects in healthy cells. MSNs were thus functionalized with sugar moieties by two different routes, either by conjugation directly to the MSN surface or mediated by a hyperbranched poly(ethylene imine), PEI layer; the latter to increase the cellular uptake by providing an overall positive surface charge as well as to increase the reaction sites for sugar conjugation. The effect of surface functionalization on the target-specific efficacy of the particles was performed by analyzing the uptake in HeLa and A549 cells as cancer cell models, as compared to mouse embryonic fibroblasts (MEF) as a representative for normal cells. To this end a comprehensive analysis strategy was employed, including flow cytometry, confocal microscopy, and spectrophotometry. When the apoptotic effect of celastrol was evaluated, the anti-cancer activity of celastrol was shown to be significantly enhanced when it was loaded into the specifically designed MSNs. The particles themselves did not induce any toxicity, and normal cells displayed minimal off-target effects. In summary, we show that glucose-functionalized MSNs can be used as highly efficient carriers for targeted celastrol delivery to achieve specific apoptosis in cancer cells.
Biomater. Sci., 2014
Aimed at utilizing high-magnetization nanospheres for magnetic field-enhanced cellular labeling, ... more Aimed at utilizing high-magnetization nanospheres for magnetic field-enhanced cellular labeling, coreshell structured sandwich-like magnetic mesoporous silica nanospheres were developed. While the magnetite cluster core can provide a high magnetic response for overcoming Brownian motion in cell culture media, the layered silica shell facilitates an efficient fluorescent dye labeling. However, the problem of particle aggregation in cell media, which is strongly enhanced under a magnetic field, significantly impeded the uptake by cells, resulting in difficulties in the precise analysis of the degree of particle internalization by fluorescence-based techniques (flow cytometry and confocal microscopy). To overcome this, reflection-based assessment was employed. Further, emphasis was put on utilizing the unique role of surface-hyperbranched polyethylenimine (PEI) in efficient prevention of particle aggregation prior to cell internalization in the presence of an external magnetic field. The interparticle attraction forces originating from magnetic dipole-dipole interactions are hereby balanced by the steric and electrostatic repulsion forces provided by the PEI functionalization, which leads to dispersed nanospheres in cell culture media during the magnetic-field induced cell labeling. As a consequence, PEI functionalization and the presence of the magnetic field synergistically enhanced the efficiency of MRI-fluorescence dual-mode labeling for cellular tracking.
Nanoscale Research Letters, 2012
In nanomedicine, physicochemical properties of the nanocarrier affect the nanoparticle's pharmaco... more In nanomedicine, physicochemical properties of the nanocarrier affect the nanoparticle's pharmacokinetics and biodistribution, which are also decisive for the passive targeting and nonspecific cellular uptake of nanoparticles. Size and surface charge are, consequently, two main determining factors in nanomedicine applications. Another important parameter which has received much less attention is the morphology (shape) of the nanocarrier. In order to investigate the morphology effect on the extent of cellular internalization, two similarly sized but differently shaped rod-like and spherical mesoporous silica nanoparticles were synthesized, characterized and functionalized to yield different surface charges. The uptake in two different cancer cell lines was investigated as a function of particle shape, coating (organic modification), surface charge and dose. According to the presented results, particle morphology is a decisive property regardless of both the different surface charges and doses tested, whereby rodlike particles internalized more efficiently in both cell lines. At lower doses whereby the shape-induced advantage is less dominant, charge-induced effects can, however, be used to fine-tune the cellular uptake as a prospective 'secondary' uptake regulator for tight dose control in nanoparticle-based drug formulations.