Drug-loaded Nanocomposites Research Articles

Ameliorating quercetin delivery in cancer therapy with polyvinyl alcohol /halloysite/starch nanocomposite

Challenges in cancer treatment can be overcome through the development of pH-responsive drug delivery systems utilizing nanocarriers. This study reports the fabrication of a novel water-in-oil-in-water (W/O/W) double nanoemulsion encapsulating quercetin (QUE), a natural anti-cancer agent. The nanocomposite, composed of starch (S), polyvinyl alcohol (PVA), and halloysite nanotubes (HNT), offers unique advantages for targeted drug delivery. Fourier-transform infrared (FTIR) spectroscopy confirmed the presence of functional groups characteristic of each component (S, PVA, and HNT) within the nanocomposite, while X-ray diffraction (XRD) analysis provided insights into its crystalline structure. Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) analysis revealed that the drug-loaded nanocomposites have a semi-spherical shape with an average size of 171.25 nm. By utilizing HNT for encapsulation, the study achieved encapsulation and drug loading efficiencies of 87 % and 46.25 %, respectively. Furthermore, the S/PVA component improved the pH-responsiveness of the nanocomposite, facilitating a sustained release of QUE as demonstrated by the in vitro release studies. Various kinetic models were applied to the experimental release data to elucidate the underlying drug release mechanisms. MTT assays and flow cytometry investigations demonstrated significant cytotoxicity of the final S/PVA/HNT/QUE nanocarrier against MCF-7 cancer cells, with evidence of increased apoptotic cell death. Based on these comprehensive findings, the S/PVA/HNT/QUE nanocarrier holds great promise as a pH-responsive drug delivery system for cancer treatment.

Nanocomposite of chitosan/gelatin/carbon quantum dots as a biocompatible and efficient nanocarrier for improving the Curcumin delivery restrictions to treat brain cancer

Curcumin (CUR) is among the most appropriate and natural-based anticancer drugs that can be applied effectively treat different classes of cancers. However, CUR suffers from a low half-life and stability in the body, which has restricted the efficacy of its delivery applications. This study is dedicated to introducing the pH-sensitive nanocomposite of chitosan (CS)/gelatin (GE)/carbon quantum dots (CQDs) as an applicable nanocarrier for enhancing CUR half-life and its delivery restrictions. The CS/GE hydrogel was synthesized by the physical crosslinking method, which improves the biocompatibility of this hydrogel. Moreover, the water-in-oil-in-water (W/O/W) double emulsion approach is involved in fabricating the drug-loaded CS/GE/CQDs@CUR nanocomposite. Afterward, drug encapsulation (EE) and loading efficiencies (LE) have been determined. Furthermore, FTIR and XRD assessments were performed to confirm the CUR incorporation into the prepared nanocarrier and crystalline features of the nanoparticles. Then, by employing Zeta potential and dynamic light scattering (DLS) analysis, the size distribution and stability of the drug-loaded nanocomposites have been assessed, which indicated monodisperse and stable nanoparticles. Furthermore, field emission scanning electron microscopy (FE-SEM) was utilized that confirmed the homogeneous distribution of the nanoparticles with smooth and quite spherical structures. In vitro drug release pattern was studied and the kinetic analysis was performed using a curve fitting technique to determine the governing release mechanism at both acidic pH and physiological conditions. The obtained outcomes from release data revealed a controlled release behavior with a 22-hour half-life, while the EE% and EL% were acquired at 46.75 % and 87.5 %, respectively. In addition, the MTT assay has been carried out on U-87 MG cell lines to evaluate the cytotoxicity of the nanocomposite. The findings showed that the fabricated nanocomposite of CS/GE/CQDs can be assumed as a biocompatible CUR nanocarrier, while the drug-loaded nanocomposite of CS/GE/CQDs@CUR showed enhanced cytotoxicity compared to the pure CUR. Based on the obtained results, this study suggests the CS/GE/CQDs nanocomposite as a biocompatible and potential nanocarrier for ameliorating CUR delivery restrictions to treat brain cancers.

Carbon-based nanocomposite decorated with bioactive glass and CoNi2S4 nanoparticles with potential for bone tissue engineering

In this work, for the first time, different forms of nanocomposites based on rGO and MWCNT were prepared in conjoining with the bioactive glass (BioGlass). In the carbonic layers, a highly toxic nanoparticle, CoNi2S4, was intercalated, and the role of this nanoparticle in the alkaline phosphatase activity, relative cell viability on different cell lines, and also the effect on the cell walls and cell morphologies were investigated. From another perspective, the ability of the chemotherapy drug loading to the prepared nanocomposites was investigated, and the use of leaf extracts was thought of as a green method to lower the cytotoxicity and regulate the genotoxicity of the generated nanocomposite. The results showed that the nanocomposites without the chemotherapy drug had higher relative cell viability than the drug-loaded nanocomposites. The relative cell viability also reached a new range when the leaf extract was applied to the surface. Thus, utilizing a leaf extract to raise the relative cell viability would be considered a novel and unique technique. From another perspective, the ALP activity of the nanocomposites, along with the toxic nanoparticles, showed promising results with the appropriate cell-seeded factors. In this regard, the morphology of the cells and the nanocomposites after seeding and treatment with each other on the hBMSCs and HEK-293 cell lines were investigated. The findings demonstrated that the shape of the nanocomposites has significantly changed in morphology as a result of the cell wall degradations and aggregations; the treated HEK-293 cell line's morphology, however, shows no significant changes after 4 h.

A novel pH- and glutathione-responsive drug delivery system based on in situ growth of MOF199 on mesoporous organic silica nanoparticles targeting the hepatocellular carcinoma niche

BackgroundFor people with advanced hepatocellular carcinoma (HCC), systemic chemotherapy remains the only choice of palliative treatment. However, chemotherapy efficacy is not effective due to its short blood circulation times, nonspecific cell and tissue biodistribution, and rapid metabolism or excretion from the body. Therefore, a targeted nanomedicine delivery system is urgently needed.MethodsIn order to improve the treatment efficiency of HCC, based on in situ growth of a copper metal organic framework on mesoporous organic silica nanoparticles, dual pH- and glutathione (GSH)-responsive multifunctional nanocomposites were synthesized as nanocarriers for enhanced HCC therapy. In this research, cellular uptake studies were performed using CLSM and Bio-TEM observations. Flow cytometry, AO-EB fluorescent staining, EdU test and Western blot were utilized to explore the apoptosis and proliferation process. In vivo imaging was employed to research the distribution of the nanocomposites in HCC tumor-bearing nude mice and the xenograft model of HCC tumor-bearing nude mice was applied to investigate the anti-tumor effects of drug-loaded nanocomposites in vivo.ResultsThis newly constructed degradable nanocomposite DOX/SOR@SP94 and mPEG-anchored MONs@MOF199 (D/S@SPMM) has the benefits of controllable pore size, high encapsulation efficiency, and precise targeting. According to the results of in vivo imaging and anti-tumor studies, as well as pharmacokinetic research, D/S@SPMM possessed precise HCC tumor targeting and long-lasting accumulation properties at the tumor region. Compared with traditional chemotherapy and non-targeted drug delivery systems, anti-tumor efficiency was increased by approximately 10- and 5-fold, respectively. The nanocomposites exhibited excellent anti-tumor properties without inducing observable systemic toxicity, owing to efficient DOX and SOR loading and release as well as the HCC specific targeting peptide SP94.ConclusionsThe in vitro and in vivo anti-tumor results indicated that these nanocomposites could be an efficient nanomedicine for targeting HCC therapy.

A Combined Isolation and Formulation Approach to Convert Nanomilled Suspensions into High Drug-Loaded Composite Particles That Readily Reconstitute

The advantage of nanoparticles to improve bioavailability of poorly soluble drugs is well known. However, the higher-energy state of nanoparticles beneficial for bioavailability presents challenges for both the stability of nanosuspensions and preventing irreversible aggregation if isolated as dry solids. The aim of this study is to explore the feasibility of an evaporation isolation route for converting wet media milled nanosuspensions into high drug-loaded nanocomposites that exhibit fast redispersion in aqueous media, ideally fully restoring the particle size distribution of the starting suspension. Optimization of this approach is presented, starting from nanomilling conditions and formulation composition to achieve physical stability post milling, followed by novel evaporative drying conditions coupled with various dispersant types/loadings. Ultimately, isolated nanocomposite particles reaching 55–75% drug load were achieved, which delivered fast redispersion and immediate release of nanoparticles when the rotary evaporator drying approach was coupled with higher concentration of hydrophilic polymers/excipients. This bench-scale rotary evaporation approach serves to identify optimal nanoparticle compositions and has a line of sight to larger scale evaporative isolation processes for preparation of solid nanocomposites particles.

Mesoporous Silk-Bioactive Glass Nanocomposites as Drug Eluting Multifunctional Conformal Coatings for Improving Osseointegration and Bactericidal Properties of Metal Implants.

Endowing metal implants with multifunctional traits to prevent implant-associated infections and improve osseointegration has become a pivotal facet in orthopedics and dental fixation. Herein, we report the synthesis of mesoporous 70S bioactive glass-silk fibroin nanocomposites inspired by the biomimetic organo-apatites of mineralized collagen. The mesoporous, biomimetic nanocomposites enabled loading of antibiotics (gentamicin and doxycycline) and favored their release in a rapid manner while preserving their bioactivity. Ease in modification of the mesoporous nanocomposites enabled tailoring of 3-(aminopropyl)-triethoxysilane to the silanol network of bioactive glass, which improved the loading capacity of the hydrophobic drug (dexamethasone). The modification favored the slow and sustained release of dexamethasone from the modified mesoporous nanocomposites, which is desired for mediating osteogenesis and immunomodulation. Conformal coatings of these drug-loaded nanocomposites were materialized on stainless-steel implants through a facile electrophoretic deposition (EPD) technique, wherein the deposition yield can be controlled by applied parameters. Antibiotic coatings exhibited antibacterial efficacy with bioactivity retained up to 28 days, while dexamethasone-loaded coatings favored mesenchymal stem cell adhesion and osteoinduction. The immunomodulatory roles were also ascertained, wherein M2 macrophage biasness was favored in dexamethasone-loaded coatings. The versatility of these mesoporous biomimetic nanocomposites guarantee the loading of scenario-specific drugs to aid their local delivery through the conformal EPD coatings developed over metal implants toward improving implant patency.

Surface-Charge-Switchable and Size-Transformable Thermosensitive Nanocomposites for Chemo-Photothermal Eradication of Bacterial Biofilms in Vitro and in Vivo.

The appearance of multidrug-resistant bacteria and their biofilms presents a serious threat to modern medical systems. Herein, we fabricated a novel gold-nanorod-based chemo-photothermal-integrated antimicrobial platform with surface-charge-switchable and near-infrared (NIR)-induced size-transformable activities that show an enhanced killing efficiency against methicillin-resistant Staphylococcus aureus (MRSA) in both planktonic and biofilm phenotypes. The nanocomposites are prepared by in situ copolymerization using N-isopropyl acrylamide (NIPAM), acrylic acid (AA), and N-allylmethylamine (MAA) as monomers on the surfaces of gold nanorods (GNRs). Ciprofloxacin (CIP) is loaded onto polymer shells of nanocomposites with a loading content of 9.8%. The negatively charged nanocomposites switch to positive upon passive accumulation at the infectious sites, which promotes deep biofilm penetration and bacterial adhesion of the nanoparticles. Subsequently, NIR irradiation triggers the nanocomposites to rapidly shrink in volume, further increasing the depth of biofilm penetration. The NIR-triggered, ultrafast volume shrinkage causes an instant release of CIP on the bacterial surface, realizing the synergistic benefits of chemo-photothermal therapy. Both in vitro and in vivo evidence demonstrate that drug-loaded nanocomposites could eradicate clinical MRSA biofilms. Taken together, the multifunctional chemo-photothermal-integrated antimicrobial platform, as designed, is a promising antimicrobial agent against MRSA infections.

Carboxymethylcellulose/polyacrylic acid/starch-modified Fe3O4 interpenetrating magnetic nanocomposite hydrogel beads as pH-sensitive carrier for oral anticancer drug delivery system

Colon cancer is the most usual illness and its oral therapy is an important challenge owing to the serious side effects on the digestive system. For this aim, novel interpenetrating magnetic nanocomposite hydrogel beads were designed based on starch-modified Fe3O4 NPs (St-Fe3O4). Carboxymethylcellulose/polyacrylic acid/starch-modified Fe3O4(CMC/PAA/St-Fe3O4) beads were prepared via a simple method. The prepared materials were fully characterized using different analyses. Anticancer doxorubicin hydrochloride (DOX) and 5-fluorouracil (5-FU) were individually loaded into the prepared nanocomposites by immersing in the solution of drugs to investigate their productivity as the loading of different anticancer drugs. In-vitro drug delivery study was performed in mimicking the gastrointestinal tract (GIT) circumstances to demonstrate the efficiency of the prepared carrier as an oral delivery system (ODS). The drug release study revealed that CMC/PAA/St-Fe3O4 nanocomposites could potentially prevent the release of 5-FU and DOX in the stomach acidic environment due to their pH-sensitive swelling manner, and also enhance the stability of drug dosing in the colorectal area. MTT assay showed significant cytotoxicity toward human colon cancer cell lines (SW480) for the drug-loaded nanocomposites; thus, they could potentially be administrated as an efficient carrier for anticancer ODS.

Synthesis and characterization of chitosan/polyvinylpyrrolidone coated nanoporous γ-Alumina as a pH-sensitive carrier for controlled release of quercetin

pH-sensitive drug delivery systems based on amphiphilic copolymers constitute a promising strategy to overcome some challenges to cancer treatment. In the present study, quercetin-loaded chitosan/polyvinylpyrrolidone/γ-Alumina nanocomposite was fabricated through a double oil in water emulsification method for the first time. γ-Alumina was incorporated to improve the drug loading efficiency and release behavior of polyvinylpyrrolidone and chitosan copolymeric hydrogel. γ-Alumina nanoparticles were obtained by the sol-gel method with a nanoporous structure, high surface area, and hydroxyl-rich surface. Quercetin, a natural anticancer agent, was loaded into the nanocomposite as a drug model. XRD and FTIR analyses confirmed the crystalline properties and chemical bonding of the prepared nanocomposite. The size of drug-loaded nanocomposites was 141 nm with monodisperse particle distribution, having a spherical shape approved by DLS analysis and FE-SEM, respectively. Incorporating γ-Alumina nanoparticles improved the encapsulation efficiency up to 95%. Besides, swelling study and the quercetin release profile demonstrated that γ-Alumina ameliorated pH sensitivity of nanocomposite and a targeted controlled release was obtained. Various release kinetic models were applied to the experimental release data to study the mechanism of drug release. Through MTT assay and flow cytometry, the quercetin-loaded nanocomposite showed significant cytotoxicity on MCF-7 breast cancer cells. Also, the enhanced apoptotic cell death confirmed the anticancer activity of γ-Alumina. These results suggest that the chitosan/polyvinylpyrrolidone/γ-Alumina nanocomposite is a novel pH-sensitive drug delivery system for anticancer applications.

Co-delivery of antibiotic and baicalein by using different polymeric nanoparticle cargos with enhanced synergistic antibacterial activity

To evaluate the effect of polymer structures on their unique characteristics and antibacterial activity, this study focused on developing amphiphilic copolymers by using three different molecules through RAFT polymerization. Three amphiphilic copolymers, namely, PBMA-b-(PDMAEMA-r-PPEGMA) (BbDrE), (PBMA-r-PDMAEMA)-b-PPEGMA (BrDbE), and PBMA-r-PDMAEMA-r-PPEGMA (BrDrE), are successfully self-assembled into spherical or oval shaped nanoparticles in aqueous solution and remain stable in PBS, LB, and 10% FBS solutions for at least 3 days. The critical micelle concentrations are 0.012, 0.025, and 0.041 mg/mL for BbDrE, BrDbE, and BrDrE, respectively. The zeta potential values under pH 5.5 and pH 7.4 conditions are 3.18/0.19, 8.57/0.046, and 2.54/-0.69 mV for BbDrE, BrDbE, and BrDrE nanoparticles, respectively. The three copolymers with similar monomer compositions show similar molecular weight and thermostability. Baicalein (BA) and ciprofloxacin (CPX) are encapsulated into the three nanoparticles to obtain BbDrE@BA/CPX, BrDbE@BA/CPX, and BrDrE@BA/CPX nanocomposites, with LC values of 63.9/78.3, 63.9/74.7, and 55.3/64.8, respectively. The two drugs are released from the three drug-loaded nanocomposites with 60%–95% release in pH 5.5 over 24 h and 15%–30% release in pH 7.4. The drug-loaded nanocomposites show synergistic antibacterial activity than the naked drug (2–8 fold reduction for CPX) or single drug-loaded nanocomposites (4–8 fold reduction for CPX) against Pseudomonas aeruginosa and Staphylococcus aureus. The drug-loaded nanocomposites inhibit the formation of bacterial biofilms above their MIC values and eliminate bacterial biofilms observed by fluorescent microscope. Finally, the nanocomposites improve the healing of infection induced by P. aeruginosa and S. aureus on rat dermal wounds. These results indicate that antimicrobial agents with different structures could be an alternative treatment strategy for bacteria-induced infection.

Novel Methotrexate-Ciprofloxacin Loaded Alginate-Clay Based Nanocomposite as Anticancer and Antibacterial Co-Drug Delivery System.

Purpose: In last decades, by increasing multi-drug resistant microbial pathogens an urgent demand was felt in the development of novel antimicrobial agents.Methods: Promising nanocomposites composed of clay/alginate/imidazolium-based ionic liquid, have been developed via intercalation of calcium alginate and ionic liquid by ion exchange method. These tailored nanocomposites were used as nanocarriers to simultaneously deliver methotrexate (MTX), and ciprofloxacin (CIP), as anticancer and antibacterial agents, respectively to MCF-7 breast cancer cells. Nanocomposites were fully characterized by scanning electron microscopy studies (SEM), X-ray diffraction (XRD), Fourier transforms infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) methods. The in vitro antimicrobial potential of the mentioned nanocomposites in free and dual-drug loaded form was investigated on Pseudomonas aeruginosa and Escherichia coli bacteria. The antitumor activity of nano-formulations was evaluated by both MTT assay and cell cycle arrest.Results: The dual drug-loaded nanocomposites with exceptionally high loading efficiency (MTX: 99 ±0.4% and CIP: 98 ±1.2%) and mean particle size of 70 nm were obtained with obvious pH-responsive MTX and CIP release (both drugs release rate was increased at pH 5.8 compared to 7.4). The antibacterial activity of CIP-loaded nanocomposites was significantly higher in comparison with free CIP (P <0.001). The antitumor activity results revealed that MTX cytotoxicity on MCF-7 cells was significantly higher in nano-formulations compared to free MTX (P <0.001). Both MTX-loaded nanocomposites caused S-phase arrest in MCF-7 cells compared to non-treated cells (P ˂ 0.001). Conclusion: Newly developed smart nanocomposites are potentially effective pH-sustainable delivery systems for enhanced tumor therapy.

Co-delivery of paclitaxel and curcumin to foliate positive cancer cells using Pluronic-coated iron oxide nanoparticles

Active targeting of folic acid and passive targeting of magnetic nanoparticles to bring about co-delivery of hydrophobic chemotherapeutic agents were the focus of this work. Co-precipitation in alkaline environment was employed for synthesizing Fe3O4 nanoparticles and stabilized by oleic acid. Aqueous dispersibility of oleic acid coated nanoparticles was brought about by folic acid modified Pluronic F127 and Pluronic F127 mixture. Folic acid is used as a targeting agent which was joined to Pluronic F127 via diethylene glycol bis(3-aminopropyl) ether spacer. The nanocomposite was used to delivery hydrophobic anticancer drugs, paclitaxel, and curcumin. Successful modification at each step was confirmed by FTIR and NMR. Quantitative analysis of attached folic acid indicated a total of 84.34% amount of conjugation. Nanoparticles characterization revealed the hydrodynamic size of and nanocomposite to be 94.2 nm nanometres. Furthermore, transmission electron micrograph reveals the size of the nanoparticle to be 12.5 nm hence also shows the superparamagnetic activity. Drug encapsulation efficiency of 34.7% and 59.5% was noted for paclitaxel and curcumin, respectively. Cytotoxic property of drug-loaded nanocomposites was increased in case of folic acid functionalized nanoparticles and further increased in the presence of an external magnetic field. Cellular uptake increased in the folic acid conjugated sample. Further many folds in the presence of an external magnetic field.Graphic abstract

Merging metal organic framework with hollow organosilica nanoparticles as a versatile nanoplatform for cancer theranostics

With great potential in nanomedicine, the integration of a metal organic framework (MOF) with a nanocarrier for smart and versatile cancer theranostics still seeks to expand. In this study, MOF was successfully merged with hollow mesoporous organosilica nanoparticles (HMONs) with a polydopamine (PDA) interlayer to form molecularly organic/inorganic hybridized nanocomposites (HMONs-PMOF). The well-defined nanostructure and favorable biocompatibility of HMONs-PMOF were demonstrated first. Doxorubicin hydrochloride (DOX) and indocyanine green (ICG) were separately loaded into the interior cavity of HMONs and the outer porous shell of MOF with high loading efficacy, respectively. The obtained dual drug-loaded nanocomposites (DI@HMONs-PMOF) displayed favorable photothermal properties and pH/NIR-triggered DOX release manner. Furthermore, in vitro cell experiments validated that HMONs-PMOF can efficiently deliver DOX into cancer cells. Upon entry into cancer cells, the photothermal effect of DI@HMONs-PMOF can induce the lysosome rupture, thereby facilitating the “lysosome escape” process and accelerating the DOX diffusion in the cytoplasm. Benefiting from the iron ion coordinated on PDA and ICG confined in MOF, magnetic resonance (MR) and photoacoustic (PA) dual-modality imaging were performed to verify the effective accumulation of DI@HMONs-PMOF at the tumor site. Interestingly, the results also suggested that the existence of ICG can cooperatively enhance the MR imaging capability of prepared nanocomposites. In addition, the significantly improved synergistic therapeutic efficacy was confirmed both in vitro and in vivo. Thus, our results indicated that the merged nanostructure of HMONs and MOF is promising for versatile cancer theranostics. Statement of SignificanceMetal organic framework (MOF) has recently emerged as a class of fascinating nanocarriers. The integration of MOF with other nanostructures can endow the new nanoformulation with collective functionality and synergistic performance that are not accessed from single-component nanostructure. Herein, we reported the successful merging of MOF and hollow mesoporous organosilica nanoparticles (HMONs) to form a hollow nanocontainer with a well-defined nanostructure. The large cavity of HMONs and highly porous network of MOF enable high drug loading efficacy. Moreover, the dual-modality magnetic resonance and photoacoustic imaging can be realized, which is also benefited from the merged nanostructure. Overall, we expected this paradigm could pave way for integrating MOF with other nanocarriers to achieve more diverse applications.

Synthesis and characterization of Fe3O4-MPTMS-PLGA nanocomposites for anticancer drug loading and release studies

Magnetic nanocomposites (Fe3O4-MPTMS-PLGA) were synthesized by single oil emulsion method and characterized by transmission electron microscopy (TEM), X-Ray diffraction (XRD), and vibrating sample magnetometer (VSM). Particle size of nanocomposites was between 117 nm and 246 nm. High performance liquid chromatography (HPLC) was used to investigate drug loading (paclitaxel, PTX) and release from Fe3O4-MPTMS-PLGA-PTX nanocomposites. The percentages of drug loading and encapsulation efficiency onto nanocomposites were found as 7.35 and 68.58, respectively. Cytotoxities of free anticancer drug and anticancer drug-loaded nanocomposites were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In vitro cell culture studies indicated that Fe3O4-MPTMS-PLGA-PTX had significant toxicity on MG-63 cancer cells.

Nanotechnology for the diagnosis and treatment of diseases.

Nanotechnology for the diagnosis and treatment of diseases.

Maghemite Functionalization for Antitumor Drug Vehiculization

In this paper we describe the preparation and characterization of magnetic nanocomposites designed for applications in targeted drug delivery. Combining superparamagnetic behavior with proper surface functionalization in a single entity makes it possible to have altogether controlled location and drug loading, and release capabilities. The colloidal vehicles consist of maghemite (γ-Fe2O3) cores surrounded by a gold shell through an intermediate silica coating. The external Au layer confers the particles a high degree of biocompatibility and reactive sites for the transported drug binding. In addition, it permits to take advantage of the strong optical resonance, making it easy to visualize the particles or even control their payload release through temperature changes. The results of the analysis of relaxivity demonstrate that these nanostructures can be used as T2 contrast agents in magnetic resonance imaging (MRI), but the magnetic cores will be mainly useful in manipulating the particles using external magnetic fields. We describe how optical absorbance and electrokinetic data provide a followup of the progress of the nanostructure formation. Additionally, these techniques, together with confocal microscopy, are employed to demonstrate that the component nanoparticles are capable of loading significant amounts of the antitumor drug doxorubicin, very efficient in the chemotherapy of a wide range of tumors. Colon adenocarcinoma cells were used to test the in vitro release capabilities of the drug-loaded nanocomposites.

Modification of magnetic silica/iron oxide nanocomposites with fluorescent polymethacrylic acid for cancer targeting and drug delivery

Biocompatible and water-soluble magnetic nanoparticles with mesoporous core-shell structure were prepared and successfully modified with a fluorescent polymer chain as a labelling segment and folic acid as the cancer targeting moiety and loaded with a drug for directional release. The porous silica oxide structure and long molecular chains of polymethacrylic acid embedded the drug efficiently in the nanocomposites and did not affect the magnetic properties of the carrier. Sustained release of the loaded drug was observed over 100 h under in vitro conditions. Furthermore, the drug carrier is able to drill into the cell membranes and obtain a sustained release of the anticancer drug into the cytoplasm. The in vitro cellular uptake of the drug demonstrated that the drug-loaded nanocomposites could effectively target the tumor cells. Our model experiments indicated that this multifunctional mesoporous core-shell magnetic nanoparticle can be exploited as an anticancer drug delivery vehicle for targeting and therapy applications.

Research of Synergetic Reversal in Adriamycin - Resistance by the Application of Magnetic Nanoparticle of Fe3O4 and Tetrandrine in K562/A02 Leukemic Cells.

Objective: To prepare functionalized Fe3O4-magnetic nanoparticles(Fe3O4-MNPs) loaded with adriamycin(ADM) or Fe3O4-MNPs co-polymerized with ADM and tetrandrine(Tet) to investigate whether the temperature, time or ratio of drug to nanoparticles influences the polymerization. To study the reversal role that the drug-loaded nano-composites play in K562 and one of its resistant cell line K562/A02 and to learn the reversal mechanism of this kind of treatments so as to provide theoretic evidence for the clinical application of them as resistance modifying agents. Method: The drug-loaded nanoparticles were prepared using mechanical absorption polymerization process in different condition of 4° or 37° for 24h or 48h. To investigate whether Fe3O4-MNPs loaded with ADM and Tet would play a synergetic reverse role in multidrug resistant cell, the drug-loaded nanoparticles by mechanical absorption polymerization were prepared to act with K562 and one of its resistant cell line K562/A02. The survival of cells which were cultured with drug-loaded nano-composites for 48h was observed through MTT assay, the growth inhibition efficacy of cells was calculated then. Using cells under the same condition described before, we took use of fluorescence microscope to measure fluorescence intensity of intracellular ADM at a wavelength of 488nm. P-glycoprotein (P-gp) was analyzed with flow cytometer. The expression of mdr1 mRNA was measured by RT-PCR. Results: The results showed that the growth inhibition efficacy of both the two cells increased with augmenting concentration of Fe3O4-MNPs which were loaded with drugs. The condition of 4° and 48h was significantly better than that of 37° and 24h respectively. Both Fe3O4-MNPs loaded with ADM or Fe3O4-MNPs co-polymerized with ADM and Tet elevated the intracellular ADM accumulation in K562/A02. However, no linear correlation was found between fluorescence intensity of intracellular adriamycin and augmenting concentration of Fe3O4-MNPs in K562/A02. Tet could downregulate the level of mdr-1 gene and decrease the expression of P-gp. Furthermore, Tet polymerized with Fe3O4-MNPs reinforced this downregulation, causing a 100-fold more decrease in mdr1 mRNA level, but did not reduce total P-gp content. Conclusions: Fe3O4-MNPs can load ADM or both ADM and Tet by mechanical absorption polymerization, which depends on proper temperature and time. Furthermore, the drug-loaded nano-composites have the ability in multidrug resistance reversal. Fe3O4-MNPs loaded with ADM or Tet can enhance the effective accumulation of the drugs in K562/A02 and Fe3O4-MNPs loaded with Tet obviously reverse multidrug resistance by reinforcing mdr1 gene downregulation. Functionalized Fe3O4-MNPs loaded with Tet probably have synergetic effect on reversal in multidrug resistance.