Enhancing the stability of nanotheranostic systems

Theranostics is new term which defined as a combination of therapy and diagnosis to establish a targeted drug delivery and monitoring of treatment into a single nanosystem. The most important parameter in the theranostic platforms is their stability to be able to increase the crossing some biological barriers and avoid the aggregation in the circulatory system. Therefore, polymeric nanoparticles are highly desirable to design novel nanotheranostics due to their improved pharmacokinetic properties, stability in physiological conditions, biocompatibility, and biodegradability. In our studies, we designed and synthesized some polymeric nanocapsules and one part of these nanocapsules utilized as a pH responsive nanosystem which includes Doxorubicin (Dox), a chemotherapeutic drug, and upconversion nanoparticles (UCNPs) as a luminescent probe and the other part of the nanocapsules were used for the photodynamic therapy (PDT) by loading the capsules with photosensitizer molecules, a derivative of Bodipy. Both studies exhibited excellent stability in phosphate buffered solutions (pH:7.4) which is proved by Zetasizer measurements, dynamic light scattering studies and stability tests. The size of the nanocapsules were dramatically decreased by increasing the stirring rate. In the first study, the nanocapsules were loaded with Dox up to ~63 % efficiency and acid-induced release (~47 %) obtained at pH 3.6 and 5.5. It was found that encapsulation decreased toxicity of UCNPs as confirmed in a cellular assay (L-929 and MCF-7 cell lines). In the second study, a higher encapsulation efficiency of Bodipy has been observed. The singlet oxygen measurements of the Bodipy encapsulated nanocapsules have been done in the presence of a trap molecule, resulted in a promising PDT activity. As a result, for both studies, a less soluble drug molecules in solution become highly soluble via encapsulation technology using a polysaccharide nanocapsule. Further studies, such as biological experiments are ongoing.No sponso

Fabrication and characterization of TiO2 nanoparticles conjugated luminescence upconversion nanoparticles

TiO2 nanoparticles conjugated luminescence upconversion (TiO2-UC) nanocomposites have been fabricated by covalently linking of carboxyl-functionalized TiO2 and amino-functionalized NaYF4:Yb3+,Er3+,Ce3+ upconversion nanoparticles (UCNP) in the presence of N,N'–dicyclohexylcarbodiimide (DCC) /4-dimethylaminopyridine (DMAP) coupling reagents. The carboxyl-functionalized TiO2 nanoparticles and amino-functionalized UCNPs have been synthesized by hydrothermal method with 5±2 and 55±10 nm in diameter, respectively. In the synthesis of UCNPs, the percentage of stabilizing agent (polyethyleneimine, PEI), the mole ratios of NaCl/NH4F and the co-doping ratio of Ce3+ ion have been found to be a significant effect on their size and morphology. Size, morphology, conjugation as well as photo-physical properties of all synthesized nanomaterials have been characterized by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and fluorescence spectroscopy. UCNPs and TiO2-UCnanocomposites exhibit strong green luminescence at room temperature under 980 nm excitation leaded the emissions at 440, 520, 540 and 658 nm, representing 2H9/2 → 4 I15/2, 2H11/2→4 I15/2, 4 S3/2→4 I15/2 and 4 F→4 I15/2 transitions, respectively. The water dispersible luminescence nanocomposites having NIR light utilizing ability are promising for efficient light harvesting and/or bio-imaging applications.No sponso

pH-responsive carboxymethyl cellulose conjugated superparamagnetic iron oxide nanocarriers

In the present study, polyethyleneimine (PEI) coated superparamagnetic iron oxide nanoparticles (SPIONs) having the size of 15 nm in diameter with high magnetic saturation (60 emu/g) have been prepared by co-precipitation method. The synthesized PEI-Fe3O4 nanoparticles have been fully characterized by transmission electron microscope (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) techniques. The free amine groups on the PEI-Fe3O4 surface has been covalently functionalized with carboxymethyl cellulose (CMC) by the catalysis of N,N'-Dicyclohexylcarbodiimide (DCC) and N, N'-Dimethylpyridin-4-amine (DMAP) coupling to produce CMC-Fe3O4 nanocarriers. The prepared CMC-Fe3O4 nanocarriers have been loaded with a well-known anti-tumor drug doxorubicin (Dox) and investigated its loading and releasing profiles from the nanocarrier. The CMC acted as an excellent nanocarrier for Dox with a loading efficiency ≈ 86%. The drug releasing profile has been studied at different pH values (3.5; 5.5; and 7.4). When the pH of the release medium (phosphate buffer solution) was changed from 7.4 to 5.5 or 3.6, the drug release has been increased which indicates that the drug releasing is pH dependent.No sponso

Bodipy photosensitizer linked hybrid nanomaterials for photodynamic therapy

Photodynamic therapy (PDT) is an alternative clinically approved treatment method to obliterate the cancerous lesion by producing reactive oxygen species (ROS) via activated photosensitizer (PS) molecule at a certain wavelength1. In recent years, Bodipy (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) as a photosensitizer molecule has been extensively investigated in PDT2,3. However, the use of many Bodipy PS in PDT has been limited due to their insolubility in aqueous solutions. Therefore, nanotechnology offers tremendous solutions to building up nano-carrier systems for insoluble molecules. We have herein developed a stable formulation of hybrid Bodipy PS via conjugation of TiO2 nanoparticles to the Bodipy PS. In this study, a heavy metal substituted Bodipy PS molecule has been synthesized and linked to polyethyleneimine (PEI) functionalized TiO2 nanoparticles to increase the stability and biocompatibility of the photosensitizer in physiological conditions (pH:7.4) as a potential photodynamic therapy agent and investigated PDT effect on CRL-4010 and MDA-MB-231 cancer cells.No sponso

Cellulose acetate encapsulated upconversion nanoparticles – a novel theranostic platform

Luminescent upconversion nanoparticles (UCNPs) are of great interest in a wide range of nanotechnological applications, particularly in the biomedical area like imaging and therapy but their biocompatibility and stability pose major challenges hampering progression towards further pharmaceutical applications. Herein, we present a biocompatible theranostic platform enabling simultaneous diagnosis and drug delivery consisting of UCNPs encapsulated with cellulose acetate (CA), a biocompatible polymer. Luminescence properties of UCNPs in the developed theranostic platform remain stable even after encapsulation. The size of the CA capsules, ranging from micro- to nano-sized particles, can easily be tuned by adjusting the stirring rate during encapsulation. Doxorubicin, a well-known chemotherapeutic drug, onto the CA nanocapsules containing UCNPs (UCNP-CA nanocapsules) was loaded with up to ~63 % efficiency and acid-induced release (~47 %) obtained at pH 3.6 and 5.5. It was found that encapsulation decreased toxicity of UCNPs as confirmed in a cellular assay (L-929 and MCF-7 cell lines). Taken together, the developed UCNP-CA nanocapsules serve as a highly interesting novel theranostic platform, combining the biocompatible optical properties of UCNP, with reduced cell toxicity and drug encapsulating properties of CA. The proposed system could be subject for further refinement and exploration.No sponso

Enhancing the stability of nanotheranostic systems

Theranostics is new term which defined as a combination of therapy and diagnosis to establish a targeted drug delivery and monitoring of treatment into a single nanosystem. The most important parameter in the theranostic platforms is their stability to be able to increase the crossing some biological barriers and avoid the aggregation in the circulatory system. Therefore, polymeric nanoparticles are highly desirable to design novel nanotheranostics due to their improved pharmacokinetic properties, stability in physiological conditions, biocompatibility, and biodegradability. In our studies, we designed and synthesized some polymeric nanocapsules and one part of these nanocapsules utilized as a pH responsive nanosystem which includes Doxorubicin (Dox), a chemotherapeutic drug, and upconversion nanoparticles (UCNPs) as a luminescent probe and the other part of the nanocapsules were used for the photodynamic therapy (PDT) by loading the capsules with photosensitizer molecules, a derivative of Bodipy. Both studies exhibited excellent stability in phosphate buffered solutions (pH:7.4) which is proved by Zetasizer measurements, dynamic light scattering studies and stability tests. The size of the nanocapsules were dramatically decreased by increasing the stirring rate. In the first study, the nanocapsules were loaded with Dox up to ~63 % efficiency and acid-induced release (~47 %) obtained at pH 3.6 and 5.5. It was found that encapsulation decreased toxicity of UCNPs as confirmed in a cellular assay (L-929 and MCF-7 cell lines). In the second study, a higher encapsulation efficiency of Bodipy has been observed. The singlet oxygen measurements of the Bodipy encapsulated nanocapsules have been done in the presence of a trap molecule, resulted in a promising PDT activity. As a result, for both studies, a less soluble drug molecules in solution become highly soluble via encapsulation technology using a polysaccharide nanocapsule. Further studies, such as biological experiments are ongoing.No sponso

Optimization of hydrothermal synthesis of Ce3+ co-doped NaYF4, Yb3+, Er3+upconversion nanoparticles and investigation of their size, morphology, and phase transitions.

In this study, the synthesis of water-soluble polyethyleneimine (PEI) modified UCNPs which were prepared by a hydrothermal method have been reported. The resultant UCNPs were small size and hexagonal β-phase structure thanks to the Ce3+ co-doping effect. Without Ce3+ ion co-doping, NaYF4,Yb3+,Er3+ (80% Y,18% Yb, 2% Er) UCNPs were micro-rods shape with ≈5 μm length and pure hexagonal phase. After introducing 3% of Ce3+ to the NaYF4,Yb3+,Er3+ (72% Y,20% Yb, 5% Er) UCNPs, the sizes of the UCNPs have been reduced to 90 nm diameter with hexagonal phase and 30 nm diameter with cubic phase. The cubic-tohexagonal phase transition process was approved by X-ray diffraction (XRD) and their sizes were also calculated from the Debye-Scherrer equation from the XRD data which are coherent with the particle size measured from transmission electron microscope (TEM). Additionally, the UCNPs display three emission bands at 520, 540 and 654 nm under 980 nm laser due to the 4f-4f transitions of Er3+ ions.No sponso

Optimization of hydrothermal synthesis of Ce3+ co-doped NaYF4, Yb3+, Er3+upconversion nanoparticles and investigation of their size, morphology, and phase transitions.

In this study, the synthesis of water-soluble polyethyleneimine (PEI) modified UCNPs which were prepared by a hydrothermal method have been reported. The resultant UCNPs were small size and hexagonal β-phase structure thanks to the Ce3+ co-doping effect. Without Ce3+ ion co-doping, NaYF4,Yb3+,Er3+ (80% Y,18% Yb, 2% Er) UCNPs were micro-rods shape with ≈5 μm length and pure hexagonal phase. After introducing 3% of Ce3+ to the NaYF4,Yb3+,Er3+ (72% Y,20% Yb, 5% Er) UCNPs, the sizes of the UCNPs have been reduced to 90 nm diameter with hexagonal phase and 30 nm diameter with cubic phase. The cubic-tohexagonal phase transition process was approved by X-ray diffraction (XRD) and their sizes were also calculated from the Debye-Scherrer equation from the XRD data which are coherent with the particle size measured from transmission electron microscope (TEM). Additionally, the UCNPs display three emission bands at 520, 540 and 654 nm under 980 nm laser due to the 4f-4f transitions of Er3+ ions.No sponso

Multifunctional magnetic nanocarrier: synthesis, characterization and pH-responsive doxorubicin release profile

ProceedingIn this study, carboxymethyl cellulose (CMC) functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have been synthesized as a novel theranostic platform which enables magnetic resonance (MR) imaging-guided and pH-responsive targeted drug delivery. In order to build up this platform, firstly, polyethyleneimine (PEI) modified SPIONs with the size of 15 nm in diameter have been preapared by coprecipitation technique. Then, the free amine groups on the PEI-SPIONs surface has been further functionalized covalently with CMC by the catalysis of N,N'-dicyclohexylcarbodiimide (DCC) and N,N'-dimethylpyridin-4-amine (DMAP) coupling to produce CMC-SPIONs. After the surface modification of PEI-SPIONs with CMC, the saturation magnetization just decreased from 60 to 58 emu/g compared to PEI-SPIONs which indicated that the CMC-SPIONs could be used as T1 agent in MRI. The resultant CMC-SPIONs have been loaded with a well-known anti-tumor durg Doxorubicin (Dox) and investigated its loading and releasing profiles from the nanocarrier. The CMC acted as an excellent nanocarrier for Dox with a loading efficinecy ≈ 86%. The drug releasing profile has been studied at different pH values (3.5; 5.5; and 7.4). The results show that when the pH of the release medium (phosphate buffer solution) was changed from 7.4 to 5.5 or 3.6, the Dox release has been incereased which indicates that the Dox releasing is pH dependent for the developed platform. The study provides a method to fabricate a multifunctional magnetic nanocarrier platform without loosing its magnetic efficiency during functionalization process and may utilize for biomedical imaging and cancer therapy.No sponso

Multifunctional magnetic nanocarrier: synthesis, characterization and pH-responsive doxorubicin release profile

ProceedingIn this study, carboxymethyl cellulose (CMC) functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have been synthesized as a novel theranostic platform which enables magnetic resonance (MR) imaging-guided and pH-responsive targeted drug delivery. In order to build up this platform, firstly, polyethyleneimine (PEI) modified SPIONs with the size of 15 nm in diameter have been preapared by coprecipitation technique. Then, the free amine groups on the PEI-SPIONs surface has been further functionalized covalently with CMC by the catalysis of N,N'-dicyclohexylcarbodiimide (DCC) and N,N'-dimethylpyridin-4-amine (DMAP) coupling to produce CMC-SPIONs. After the surface modification of PEI-SPIONs with CMC, the saturation magnetization just decreased from 60 to 58 emu/g compared to PEI-SPIONs which indicated that the CMC-SPIONs could be used as T1 agent in MRI. The resultant CMC-SPIONs have been loaded with a well-known anti-tumor durg Doxorubicin (Dox) and investigated its loading and releasing profiles from the nanocarrier. The CMC acted as an excellent nanocarrier for Dox with a loading efficinecy ≈ 86%. The drug releasing profile has been studied at different pH values (3.5; 5.5; and 7.4). The results show that when the pH of the release medium (phosphate buffer solution) was changed from 7.4 to 5.5 or 3.6, the Dox release has been incereased which indicates that the Dox releasing is pH dependent for the developed platform. The study provides a method to fabricate a multifunctional magnetic nanocarrier platform without loosing its magnetic efficiency during functionalization process and may utilize for biomedical imaging and cancer therapy.No sponso