Doxorubicin Nanocarriers Research Articles

β-Cyclodextrin-functionalized mesocellular silica foams as nanocarriers of doxorubicin

In this work, the preparation of inclusion complexes by functionalizing mesocellular silica foam (MCF) with β-cyclodextrin (β-CD) is reported. Likewise, the effect of the grafted β-CD amount on the loading and release of doxorubicin (Dox) at simulated physiological and lysosomal pH was studied. First, MCF silica was functionalized with β-CD under different conditions by means of reflux in toluene. The materials obtained were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), small-angle X-ray scattering (SAXS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). By means of TGA, the grafting percentage of β-CD onto MCF was determined, obtaining a grafting range from 10 to 40%. The drug was loaded into the inclusion complexes by immersion in an aqueous Dox solution and then the release was studied at different pH values (7.4, 5.0) at 37 ​°C. The results suggested that the silica materials modified with β-CD could act as drug carriers in the sustained and directed administration of this anticancer agent, loading up to 1.17 ​× ​10−1 mg Dox/mg MCF-(β-CD) in 72 ​h and releasing up to 70%. Kinetically, the release profiles of the inclusion complexes were better adjusted to the Higuchi model, suggesting that release was carried by diffusion of drug from the inclusion complex to the simulated pH medium.

The toxicity performance of pH-responsive doxorubicin nanocarrier with different drug loading strategy

To improve the water solubility, keep drug loading rate and reduce toxic side effects of chemotherapeutic drugs, two kinds of pH–responsive nanoparticles (denoted as HDOX and PDOX) were prepared to achieve controlled release of drugs and their toxicity against tumor cells were studied. The HDOX was synthesized to incorporate doxorubicin (DOX) via a pH-responsive chemical hydrazone bond, while the PDOX was a pH-responsive polymer-coated nanoparticle to load DOX. The drug loading was measured by fluorescence spectroscopy. The drug release performances in vitro were investigated under different simulated conditions, as well as the toxicity of two NPs were evaluated by the MTT assay. In vitro experiments showed that HDOX (∼15 wt %) has a superior drug-loading ratio compared to PDOX (∼10 wt %). Besides, HDOX and PDOX also displayed a higher stability in normal physiological environment. After the nanoparticles were internalized by the tumor cells, the nanoparticles could transport to the entire tumor cells and showed a pH-responsive drug release behavior. In vivo experiments confirmed excellent biological safety of the two nanoparticles. These results demonstrated that nanocarrier-based chemical bonding strategy provided advantages for the development pH-responsive nanomedicine for cancer therapy.

Preparation and characterization of nanocomposites based on poly(N-vinycaprolactam) and magnetic nanoparticles for using as drug delivery system

In this work, magnetite nanoparticles (Fe3O4 NPs) were grafted with poly (N-vinylcaprolactam) (PNVCL) chains via free radical polymerization for being used as carrier of doxorubicin (DOX). Grafting of PNVCL on these magnetic NPs was corroborated by studies of X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). The in vitro DOX release was studied at physiological temperature in phosphate buffer solution 7.4. Also, hemolysis assays were carried out in order to investigate the biocompatibility of the magnetic nanocomposites. Composite nanoparticles exhibited a spherical morphology with a magnetic core and a polymer layer. The polymer-grafted magnetite NPs showed a high hemobiocompatibility with DOX encapsulation efficiency of about 35–47% and a maximum DOX cumulative in vitro release of 42% which depended of the polymer content in the nanocomposite. These results show that obtained magnetic functional nanocomposites could have the potential to be used as nanocarriers of DOX.

Comparison between novel star-like redox-sensitive amphiphilic block copolymer and its linear counterpart copolymer as nanocarriers for doxorubicin

Linear and star-like redox-sensitive amphiphilic block copolymers have been studied as anticancer drug delivery systems. However, few reports directly compared the properties of those two structures especially when they are used as nanocarriers for antitumor drugs. To address this, a novel star-like copolymer and its linear counterpart were synthesized with a hydrophobic/redox-responsive/hydrophilic structure. The overall molecular weight of the star-shaped copolymer was nearly equal to that of the linear counterpart. The star-like micelles exhibit size of 90 nm, which was smaller than that of linear copolymers (151.6 nm) and critical micelle concentration of 1 mg/L, which was lower than that of the linear micelles (8.9 mg/L). The disassembly behaviors and the redox-sensitivity of the nanoparticles to reductive stimuli of glutathione was evaluated from the changes of the micellar size and morphology. Furthermore, doxorubicin was physically loaded into the hydrophobic part of the copolymers. The drug-loading capacities in the star-like and linear micelles were 15.94 and 7.53 wt%, respectively. Drug release studies carried out at two different glutathione concentrations. A cytotoxicity study of the micelles was performed by MTT assay. The prepared star copolymer showed no significant toxicity against HDF cells while enhanced cytotoxicity of the DOX-loaded micelles against MCF-7 cells was observed. Therefore, developing sucrose-PCL-SS-PEG copolymer reported in this paper as an effective reduction-responsive carrier with excellent properties and cell biocompatibility is promising for the efficient intracellular delivery of hydrophobic chemotherapeutic drugs. This work also indicates that modification of the nanocarrier structure is a potential strategy for optimizing drug delivery.

Synergistic Treatment of Tumor by Targeted Biotherapy and Chemotherapy via Site-Specific Anchoring of Aptamers on DNA Nanotubes.

BackgroundAptamers have been widely used as targeted therapeutic agents due to its relatively small physical size, flexible structure, high specificity, and selectivity. Aptamers functionalized nanomaterials, not only enhance the targeting of nanomaterials, but can also improve the stability of the aptamers. We developed aptamer C2NP (Apt) conjugated straight DNA nanotubes (S-DNT-Apt) and twisted DNA nanotubes (T-DNT-Apt) as nanocarriers for doxorubicin (DOX).MethodsThe twisted DNA nanotubes (T-DNT) and straight DNA nanotubes (S-DNT) were assembled with a scaffold and hundreds of staples. Apt was site-specifically anchored on DNA nanotubes with either different spatial distribution (3 or 6 nm) or varied stoichiometry (15Apt or 30Apt). The developed nanocarriers were characterized with agarose gel electrophoresis and transmission electron microscopy. The drug loading and release in vitro were evaluated by measuring the fluorescence intensity of DOX using a microplate reader. The stability of DNT in cell culture medium plus 10% of FBS was evaluated by agarose gel electrophoresis. The cytotoxicity of DNA nanostructures against K299 cells was tested with a standard CCK8 method. Cellular uptake, cell apoptosis, cell cycle and reactive oxygen species level were investigated by flow cytometry. The expression of p53 was examined by Western Blot.ResultsT-DNT-30Apt-6 exhibited the highest cytotoxicity when the concentration of Apt was 120 nM. After intercalation of DOX, the cytotoxicity of DOX@T-DNT-30Apt-6 was further enhanced due to the combination of chemotherapy of DOX and biotherapy of Apt. The enhanced cytotoxicity of DOX@T-DNT-30Apt-6 can be explained by the increase in the cellular uptake, cell apoptosis and intracellular ROS levels. Additionally, the interaction between Apt and its receptor CD30 could upregulate the expression of p53.ConclusionThese results demonstrate that both stoichiometry and spatial arrangement of Apt on T-DNT-Apt influence the anticancer activity. The developed twisted DNA nanotubes may be a solution for the synergistic treatment of cancer.

PEGylation of graphene/iron oxide nanocomposite: assessment of release of doxorubicin, magnetically targeted drug delivery and photothermal therapy

Scientists have recommended to investigate graphene and graphene base compounds for their potential uses in a variety of fields, such as biomedicine and drug release. A PEGylated and functionalized magnetic graphene oxide (MG–NH2–PEG) complex was used herein as a nanocarrier of Doxorubicin, a cancer chemotherapy drug. First, graphene oxide was synthesized by modified Hummer’s method and then functionalized with amine groups (G–NH2). Afterwards, solvothermal of Fe3O4 magnetic nanoparticles on G–NH2 to prepare magnetic graphene oxide (MGO) modified by MG–NH2 via covalent bindings for the synthesis of MG–NH2–PEG. Doxorubicin (DOX) was loaded onto MG–NH2–PEG at pH 7 by the use of π–π interactions, yielding a highly significant value of DOX's loading efficiency along with its loading content. In vitro cytotoxicity tests on MCF-7 cells line were carried out for MG–NH2–PEG: DOX according to the drug loading and release characteristics. The results of standard MTT assay for the toxicity determination of both synthetic nanocomposites and the drug revealed over 85% of surviving cells after 48 h, with a cellular uptake of > 80%, suggesting a satisfactory outcome on the non-toxicity of the nanocomposite. It can, therefore, be concluded that MG–NH2–PEG showed to be an effective drug carrier in cancer chemotherapy drug delivery through loading the above drugs of low medicinal properties with individual dependency on pH levels. Furthermore, MG–NH2–PEG represent strong optical absorbance from the visible to the near-infrared (NIR) region, and can be utilized for localized photothermal ablation of cancer cells guided by the magnetic field.

Doxorubicin Loading on Functional Graphene as a Promising Nanocarrier Using Ternary Deep Eutectic Solvent Systems

The application of graphene in the field of drug delivery has attracted massive interest among researchers. However, the high toxicity of graphene has been a drawback for its use in drug delivery. Therefore, to enhance the biocompatibility of graphene, a new route was developed using ternary natural deep eutectic solvents (DESs) as functionalizing agents, which have the capability to incorporate various functional groups and surface modifications. Physicochemical characterization analyses, including field emission scanning electron microscope, fourier-transform infrared spectroscopy, Raman spectroscopy, Brunauer−Emmett−Teller, X-ray diffraction, and energy dispersive X-ray, were used to verify the surface modifications introduced by the functionalization process. Doxorubicin was loaded onto the DES-functionalized graphene. The results exhibited significantly improved drug entrapment efficiency (EE) and drug loading capacity (DLC) compared with pristine graphene and oxidized graphene. Compared with unfunctionalized graphene, functionalization with DES choline chloride (ChCl):sucrose:water (4:1:4) resulted in the highest drug loading capacity (EE of 51.84% and DLC of 25.92%) followed by DES ChCl:glycerol:water (1:2:1) (EE of 51.04% and DLC of 25.52%). Following doxorubicin loading, graphene damaged human breast cancer cell line (MCF-7) through the generation of intracellular reactive oxygen species (>95%) and cell cycle disruption by increase in the cell population at S phase and G2/M phase. Thus, DESs represent promising green functionalizing agents for nanodrug carriers. To the best of our knowledge, this is the first time that DES-functionalized graphene has been used as a nanocarrier for doxorubicin, illustrating the potential application of DESs as functionalizing agents in drug delivery systems.

Erythrocyte membrane vesicles coated biomimetic and targeted doxorubicin nanocarrier: Development, characterization and in vitro studies

Ovarian cancer is the most common cause of death within gynecologic cancers and doxorubicin is an anthracycline agent, is widely used in many cancer types. Folate receptor enables of accumulation folate linked nanoparticles into tumor cells and magnetic targeting also provides localized addressing. The aim of this work is to develop a magnetic and biomolecularly targeted biomimetic doxorubicin nanocarrier system for ovarian cancer therapy. Firstly, highly dispersed starch and PEG diacid coated magnetic nanoparticles were synthesized with an easy and fabricable method and 91.45 ± 1.07 μg doxorubicin was adsorbed on per mg magnetic nanoparticles. The structure was verified with FTIR, TGA, VSM, TEM and zetasizer. Then, folate linked erythrocyte membrane vesicles were prepared from ghost cells and doxorubicin loaded magnetic nanoparticles were encapsulated into vesicles through extrusion due to enabling avoidance from immun clearance. The final nanocarrier system was nearly spherical in shape and had a hydrodynamic size of 157.4 ± 33.2 nm. Drug release profile was determined as in a controlled manner and IC50 value against SKOV3 for 72 h was calculated as 0.74 ± 0.32 μg/mL which was lower than that of free doxorubicin. In conclusion, it was suggested that biomimetic doxorubicin nanocarrier system have many advantages for targeted ovarian cancer therapy.

On-demand CO release for amplification of chemotherapy by MOF functionalized magnetic carbon nanoparticles with NIR irradiation

Carbon monoxide (CO) gas therapy combined with chemotherapy and photothermal therapy (PTT) is a promising treatment mode for malignant tumor. Herein, we firstly reported doxorubicin (DOX) loaded Mn carbonyl modified Fe (Ⅲ)-based nanoMOFs (MIL-100) coated PEGylated magnetic carbon nanoparticles (denoted as MCM@PEG-CO-DOX NPs) as theranostics nanoplatforms for near-infrared (NIR)-responded CO-DOX combination therapy. MIL-100 as a good nanocarrier of DOX with high loading capacity can also chelate the Mn carbonyl after a smart modification. Meanwhile, magnetic carbon core possessed photothermal effect, which can convert the NIR light to heat by an 808 nm laser irradiation, resulting in the on-demand release of CO and DOX. As a result, combining with PTT, MCM@PEG-CO-DOX NPs killed tumor efficiently. Moreover, our synthesized MCM@PEG-CO-DOX NPs were capable of realizing tumor dual-mode imaging including magnetic resonance imaging (MRI) and photoacoustic imaging (PAI).

Gelatin-poly (ethylene glycol) methyl ether-functionalized porous Nanosilica for efficient doxorubicin delivery

Porous nanosilica (PNS) has been receiving wider attention in the fabrication of nanocarriers for drug delivery. However, unmodified PNS nanoparticles have shown an initial rapid release of encapsulated drugs, which may limit their potential applications in the clinical setting. In this report, in order to improve the efficiency of drug delivery, PNS nanoparticles were first synthesized and then surface conjugated with gelatin-poly (ethylene glycol) methyl ether (GEL-mPEG) to form PNS-GEL-mPEG nanocarriers for doxorubicin (DOX) delivery. The co-polymer structure and morphology of the obtained nanocarriers were analyzed using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The loading capacity, encapsulation efficiency and DOX release behavior of DOX@PNS-GEL-mPEG nanocarriers were also evaluated. Results showed that the conjugated PNS nanocarriers were spherical shape with an average diameter of 69.60 ± 3.27 nm, as compared to 58.93 ± 2.42 nm of PNS nanocarriers. Also, the PNS-GEL-mPEG nanoparticles showed their ability to effectively encapsulate DOX. In detail, DOX was significantly encapsulated into PNS-GEL-mPEG nanocarriers to form DOX@PNS-GEL-mPEG nanocarriers with high loading efficiency of 85.88 ± 0.15%. Moreover, the synthesized DOX@PNS-GEL-mPEG nanoparticles exhibited a sustainable release of DOX up to 96 h, without a burst release, as compared with less than 2 h from unconjugated PNS nanocarriers, and exhibited a pH-dependent drug release behavior of DOX in acidic media. These results indicated that DOX@PNS-GEL-mPEG nanocarriers have high potential applications for efficient DOX loading and release in cancer therapy.

GSH and enzyme responsive nanospheres based on self-assembly of green tea polyphenols and BSA used for target cancer chemotherapy

Developing safe and effective stimuli-responsive nanocarriers is very important for tumor chemotherapy. In this work, bovine serum albumin (BSA) and green tea polyphenol (TP) were used to prepare glutathione (GSH) and enzyme (trypsin) responsive nanocarriers for doxorubicin (DOX). These nanocarriers were further modified with folate, briefly named as DOX@BSA-TP-FA NSs. The diameter of nanocarriers was about 220 nm. The DOX loading efficiency and loading amount were 86.4% and 23.5 wt%, respectively. The cellular uptake, apoptosis, and GSH and trypsin responsive release properties of these nanocarriers were investigated.

Preparation and characterization of doxorubicin nanocarriers based on thermoresponsive oligo(ethylene glycol) methyl ether methacrylate polymer-drug conjugates

Aggregation of thermoresponsive chains to form mesoglobules is a promising way to make nanoaggregates useful as drug carriers. Here, we present for the first time, a route for the formulation of mesoglobules that may be used as polymer carriers for doxorubicin (DOX). For this purpose, a thermoresponsive terpolymer composed of diethylene glycol methyl methacrylate, oligoethylene glycol methyl methacrylate (300 g/mol), and 2-aminoethyl methacrylate hydrochloride was synthesized. Amino groups of polymers have been modified to azide or prop-2-yn-1-yl carbamate groups. Azide groups were used to conjugate modified DOX to polymer chains by the Huisgen cycloaddition reaction. The temperature aggregation of terpolymers, polymer-DOX conjugate and their mixtures was examined. Drug nanocarriers were formed by “click” crosslinking of thermally coaggregated mesoglobules of the conjugate and terpolymer with alkyne groups. Hydrolysable carbamate bonds allows for the nanoparticles disintegration and release of drug at various pH levels (5.5 and 7.4), with and without enzyme.

Newly emerging mesoporous strontium hydroxyapatite nanorods: microwave synthesis and relevance as doxorubicin nanocarrier

A new synthesis method is developed for preparation of mesoporous strontium hydroxyapatite (SrHAp) nanorods using CEM Discover microwave synthesizer. Nanorods preparation with surfactants SrHAp(+) and without surfactants SrHAp(−) were successfully achieved at 160 °C temperature and 15 min of hold time. Particle sizes with standard deviation were found to be 67 ± 18 and 69 ± 24 nm respectively. Mesoporous nanorods were thoroughly characterized using different methods, such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field-emission gun transmission electron microscopy (FEG-TEM), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) surface area and porosity measurement. It was observed that use of trisodium citrate and CTAB resulted in quite agglomerated particles, whereas nanorods synthesized without citrate and CTAB were well dispersed. Cell toxicity of both these materials synthesized was tested in MCF-7 and Zr-75 cell lines using MTT assay. SrHAp nanorods concentration up to 0.25 mg/ml was non-toxic at 48 hours (h) time point in both the cell lines. As SrHAp(−) were found to serve better in terms of cytotoxicity, they were chosen for doxorubicin (Dox) loading, pH depended release and cell uptake study. The successful loading of Dox was ascertained by UV-Visible and FTIR spectroscopy. Entrapment efficiency of Dox in SrHAp nanoparticles was found to be 83.71%, and loading capacity was 0.017 μg Dox per μg SrHAp nanoparticles. Rapid release was observed in the initial hours followed by slow release. Even until 31 days, only 27 and 32% drug was released at pH 7.4 and pH 4.5 respectively, which shows controlled release behavior. Further, cellular uptake of Dox-loaded nanoparticles at different time points was studied in the two breast cancer cell lines by fluorescence imaging. These nanoparticles were found to internalize within both these cells after 3 h of incubation and continued further until 24 h. Overall, high Dox loading efficacy, sustained release behavior, and cell uptake potential render SrHAp nanoparticles to give promising results when applied in vivo and emerge as a robust drug carrier towards solving purpose of slow and prolonged drug release.

Organic solvent-free preparation of keratin nanoparticles as doxorubicin carriers for antitumour activity

Doxorubicin is one of the most effective chemotherapeutic agents for the treatment of several neoplastic conditions, such as leukemia, neuroblastoma, soft tissue and bone sarcomas, breast cancer, ovarian cancer and others. However, its clinical application is limited by cardiotoxicity, such as cardiomyopathy, that once developed carries a poor prognosis and is frequently fatal. The controlled release of doxorubicin by means of a smart carrier is a strategy to overcome the aforementioned drawback. Herein, doxorubicin/keratin nanoparticles were prepared by loading the drug through ionic gelation and aggregation methods, without using cross linkers, organic solvents neither surfactants. Both methodologies afford nanoparticles with yields up to 100 wt%, depending on the loading amount of doxorubicin. Although aggregation yield smaller nanoparticles (≈100 nm), ionic gelation allows a higher drug loading (up to 30 wt%,). More importantly, nanoparticles obtained through this procedure display a pH-responsive release of the drug: indeed Peppas-Salhin model suggests that, the doxorubicin release mechanism is predominantly controlled by diffusion at pH 7.4 and by protein swelling at pH 5.Moreover, nanoparticles prepared by ionic gelation resulted in more efficient cell killing of MDA-MB-231 and MCF-7 breast cancer cells than those prepared by aggregation. Based on the herein presented preliminary results, ionic gelation emerges as a promising approach for the preparation of keratin-based doxorubicin nanocarriers for cancer therapy, that is worth to further investigate.

Magnetic Nanocarrier Containing 68Ga–DTPA Complex for Targeted Delivery of Doxorubicin

In the present study, a multifunctional pH-sensitive nanocarrier was prepared for targeted drug delivery in chemotherapy with potential usage in magnetic and nuclear medicine imaging. The Fe3O4@SiO2 core–shell nanoparticles were initially prepared, functionalized with aminopropyltriethoxysilane (APTES), grafted with diethylenetriaminepentaacetic acid ligand (DTPA), and conjugation with an anti-cancer drug, doxorubicin (DOX). DOX was covalently linked via an amine group with carboxylic acid groups of DTPA. The amide bonds between the drug and the ligand were enabled to cleave in acidic pH (i.e. 5.5), and subsequently, the drug was released in slow fashion (85 wt% within 4 h). The superparamagnetic core in the carrier allows the targeted delivery of drug to the cancer tumor sites using external magnetic fields. Magnetic nanocarriers could also be used in magnetic resonance imaging (MRI). Radiolabelling of the carrier was carried through a chelation of Ga(III) ion by DTPA that can be used for positron emission tomography. It is expected that the multi-modal nanocarrier, Fe3O4@SiO2–APTES–DTPA–Ga–DOX, can have theranostic (therapeutic and diagnostic) applications. Fe3O4@SiO2–APTES–DTPA–Ga–DOX nanocarrier is produced for pH-controlled release drug delivery system. The carrier can be used in medical diagnosis due to its magnetic and radiolabeling features.

A pH-triggered charge reversal and self-fluorescent micelle as a smart nanocarrier for doxorubicin controlled release

A novel pH-sensitive charge reversal and self-fluorescent polymeric micelle is designed and synthesized successfully. The smart micelle is prepared based on MPEG-polyurethane multi-block copolymer, which is synthesized by polycondensation, with 1, 4-bis (hydroxyethyl) piperazine (HEP) and hydroxyl-sulfamethazine (Hydroxyl-SM) as pH-sensitive molecules and fluorescein isothiocyanate (FITC) as fluorescent segment. The resulting MPEG-polyurethane multi-block copolymer is examined by 1H–NMR, UV-vis spectra, fluorescence spectra and an acid-base titration. Moreover, the diameter, morphology and cytotoxicity of obtained polymer micelle are measured by dynamic light scattering (DLS), transmission electron microscopy (TEM) and MTT assay. The results indicate that the micelle has a small diameter of less than 200 nm and can remain unchanged within two weeks. Zeta-potential measurement shows that the negative charge of micelle can switch into positive charge as the pH value decreasing from 9.0 to 3.0. Subsequently, the fluorescence intensity decreases significantly with the reducing of pH values. The MTT assay shows the low cytotoxicity and good biocompatibility of the MPEG-polyurethane polymeric micelles. Finally, doxorubicin (DOX) is loaded into micelles to detect in vitro release behavior. The drug loaded micelles show a faster release behavior at pH 5.0 than that at pH 7.4. Therefore, the pH-sensitive charge reversal and self-fluorescent micelle can be a potential smart carrier for delivery and controlled release of protein drug.

Hybrid ZnPc@TiO2 nanostructures for targeted photodynamic therapy, bioimaging and doxorubicin delivery

In this study ZnPc@TiO2 hybrid nanostructures, both nanoparticles and nanotubes, as potential photosensitizers for the photodynamic therapy, fluorescent bioimaging agents, as well as anti-cancer drug nanocarriers, were prepared via zinc phthalocyanine (ZnPc) deposition on TiO2. In order to provide the selectivity of prepared hybrid nanostructures towards cancer cells they were modified with folic acid molecules (FA). The efficient attachment of both ZnPc and FA molecules was confirmed with dynamic light scattering (DLS), zeta potential measurements and X-ray photoelectron spectroscopy (XPS). It was presented that ZnPc and FA attachment has a strong effect on fluorescence emission properties of TiO2 nanostructures, which can be further used for their simultaneous visualization upon cellular uptake. ZnPc@TiO2 and FA/ZnPc@TiO2 hybrid nanotubes were then employed as doxorubicin nanocarriers. It was demonstrated that doxorubicin can be easily loaded on these hybrid nanostructures via an electrostatic interaction and then released. In vitro cytotoxicity and photo-cytotoxic activity studies showed that prepared hybrid nanostructures were selectively targeting to cancer cells. Doxorubicin loaded hybrid nanostructures were significantly more cytotoxic than un-loaded ones and their cytotoxic effect was even more severe upon irradiation. The cellular uptake of prepared hybrid nanostructures and their localization in cells was monitored in vitro in 2D cell culture and tumor-like 3D multicellular culture environment with fluorescent confocal microscopy. These hybrid nanostructures preferentially penetrated into human cervical cancer cells (HeLa) than into normal fibroblasts (MSU-1.1) and were mainly localized within the cell cytoplasm. HeLa cells spheroids were also efficiently labelled by prepared hybrid nanostructures. Fluorescent imaging of Hela cells treated with doxorubicin loaded hybrid nanostructures showed that doxorubicin was effectively delivered into cells, released and evenly distributed in the cytoplasm. In conclusion, prepared hybrid nanostructures exhibit high potential as selective bioimaging agents next to their photodynamic activity and drug delivery ability.

Synthesis and characterization of poly(propylene imine)-dendrimer-grafted gold nanoparticles as nanocarriers of doxorubicin

The aim of current work is synthesis 4th-generation-poly(propylene imine) (PPI)-dendrimer modified gold nanoparticles (Au-G4A) as nanocarriers for doxorubicin (DOX) and studying in vitro drug release kinetics from nanocarriers into different media. Accordingly, AuNPs were synthesized by reduction of chloroauric acid (HAuCl4) aqueous solution with trisodium citrate and modified with cysteamine to obtain amine-functionalized (Au-NH2) nanoparticles. Au-NH2 nanoparticles were used as multifunctional cores and participated in Michael addition of acrylonitrile and reduction process by lithium aluminum hydride (LAH) to synthesize Au-G4A nanoparticles. Also, peripheral primary amine groups of Au-G4A were conjugated with folic acid (FA) (Au-G4F) to study the bioconjugation effect on drug release behavior of nanostructures. Ultraviolet spectroscopy (UV–vis), atomic force microscopy (AFM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) were used to approve the synthesis of different nanostructures. Finally, Au-G4A and Au-G4F samples were loaded with DOX and exposed to environments with different pH values to examine the release properties of nanostructures. Also, drug release kinetics was investigated by fitting of experimental data with different release models. As a result, synthesized dendritic structures showed Higuchi and Korsmeyer-Peppas models release behavior due to better solubility of drug in release media with respect to dendrimer cavities and drug release through polymeric matrix respectively.

New doxorubicin nanocarriers based on cyclodextrins.

Polymeric nanoparticles and fibrin gels (FBGs) are attractive biomaterials for local delivery of a variety of biotherapeutic agents, from drugs to proteins. We combined these different drug delivery approaches by preparing nanoparticle-loaded FBGs characterized by their intrinsic features of drug delivery rate and antiproliferative/apoptotic activities. Inclusion complexes of doxorubicin (DOXO) with oligomeric β-cyclodextrins (oCyD) functionalized with different functional groups were studied. These nanocarriers were able to interact with FBGs as shown by a decreased release rate of DOXO. One of these complexes, oCyDNH2/DOXO, demonstrated good antiproliferative and apoptotic activity in vitro, reflecting a higher drug uptake by cells. As hypothesized, the nanocarrier/FBG complexes showed a lower drug release rate than similar FBGs loaded with the corresponding non-functionalized oCyD/DOXO. Taken together, our results provide experimental evidence that oCyDNH2/DOXO complexes may be useful components in enhanced FBGs and further build support for the great promise these complex molecules hold for clinical use in localized anticancer therapy of inoperable or surgically removable tumors of different histological origin.

Discovery of a new function of curcumin which enhances its anticancer therapeutic potency.

Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.