Doxorubicin Nanocarriers Research Articles

Magnetic alginate core-shell nanoparticles based on Schiff-base imine bonding for pH-responsive doxorubicin delivery system

This research describes the development of a novel pH-responsive drug delivery system (DDS) based on sodium alginate (SA) and magnetic nanoparticles (MNPs) for cancer treatments. One possible approach to creating a wide variety of functional nanoparticles is to graft functional materials onto magnetite nanoparticles. In this study, we demonstrate the effective alteration of Fe3O4 nanoparticles using the alginate dialdehyde (ADA) group through a Schiff-Base imine reaction toward synthesizing Fe3O4@SiO2@APTMS@ADA (FSA@ADA) nanocarrier (NC). doxorubicin (DOX) as an anticancer drug was loaded (about 93 % drug loading capacities) on the FSA@ADA NC through chemical and physical interactions. doxorubicin (DOX) as an anticancer drug was loaded (about 93 % drug loading capacities) on the FSA@ADA NC through chemical and physical interactions. The synthesized nanocarriers were thoroughly characterized by various techniques, including FT-IR, FE-SEM, EDX-MAP, TEM, XRD, VSM, TGA, and 1HNMR. In vitro DOX release studies showed a pH-dependent manner and its release rate is lower (< 15 %) at 7.4 than pH 5 (about 75 %) over 25 days. Cytotoxicity results showed good biocompatibility for blank FSA@ADA (over about 85 % cell viability), whereas DOX-loaded FSA@ADA NCs had higher cytotoxic effects (IC50 value: ∼6 µg/mL) as a result of the controlled release of DOX into HeLa cells. Results showed that the magnetic core-shell FSA@ADA/DOX NC has the potential to be used as a targeted stimuli-responsive drug for cancer treatment.

Nanoplatform based on carbon nanoparticles loaded with doxorubicin enhances apoptosis by generating reactive oxygen species for effective cancer therapy.

At present, due to its wide application and relatively low cost, chemotherapy remains a clinically important cancer treatment option; however, a number of chemotherapeutic drugs have important limitations, such as lack of specificity, high toxicity and side effects, and multi-drug resistance. The emergence of nanocarriers has removed numerous clinical application limitations of certain antitumor chemotherapy drugs and has been widely used in the treatment of tumors with nanodrugs. The present study used carbon nanoparticles (CNPs) as a nanocarrier for doxorubicin (DOX) to form the novel nanomedicine delivery system (CNPs@DOX)was demonstrated by UV-vis and fluorescence spectrophotometry, ζ potential and TEM characterization experiments. The results confirmed the successful preparation of CNPs@DOX nanoparticles with a particle size of 96±17 nm, a wide range of absorption and a negatively charged surface. Furthermore, CNPs@DOX produced more reactive oxygen species and induced apoptosis, and thus exhibited higher cytotoxicity than DOX, which is a small molecule anticancer drug without a nanocarrier delivery system.. The present study provides a strategy for the treatment of tumors with nanomedicine.

Preparation, Optimization and In vitro Evaluation of Doxorubicin-loaded into Hyaluronic Acid Coated Niosomes Against Breast Cancer.

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.

Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/β-catenin signaling pathway in C26 colorectal cancer cells

Zymosan is a β-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV–Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/β-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/β-catenin signaling and apoptosis.

Poly(N-vinylcaprolactam-co-2-(diethylamino)ethylmethacrylate) coated Fe3O4@SiO2 core-shell magnetic nanoparticles for controlled doxorubicin delivery

Hybrid materials based on magnetite nanoparticles coated with silica (SiO2) and a temperature-pH dual-responsive copolymer were synthesized. First, magnetite nanoparticles (Fe3O4NPs) were functionalized with oleic acid (OA) by the coprecipitation method to give Fe3O4NPs-OA. Then, these nanoparticles (NPs) were coated with SiO2 by reverse microemulsion to obtain Fe3O4[email protected]2. Subsequently, Fe3O4[email protected]2 were modified with vinyltrimethoxysilane (VTMS) to graft poly(N-vinylcaprolactam-co-(2-(diethylamino)ethylmethacrylate) (poly(NVCL-co-DEAEMA)) by free radical polymerization. The functionalization and grafting of this copolymer were corroborated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), and transmission electron microscopy (TEM). Doxorubicin (DOX) was loaded and then released at different pH values (7.4 and 5.0) and temperatures (25 and 37 °C). Overall, the release percentages were dependent on the pH, with the maximum release rate at pH 5.0 being 71%. The release kinetics study fits the Korsmeyer-Peppas model and suggests that the amount of drug released occurs by diffusion. Hemolysis test of the selected Fe3O4[email protected]2-g-poly(NVCL-co-DEAEMA) hybrid material showed hemolytic activity of less than 5% at concentrations up to 250 μg/mL. These results suggest that the hybrid materials obtained may have great potential to be used as DOX nanocarriers.

PH-/Redox-Responsive Nanodroplet Combined with Ultrasound-Targeted Microbubble Destruction for the Targeted Treatment of Drug-Resistant Triple Negative Breast Cancer.

Multiple drug resistance (MDR) exists in divergent cancers including triple negative breast cancer (TNBC) and partly results in the resistance to many first-line anti-cancer agents, bringing a big challenge to TNBC management. To develop novel TNBC therapeutics, in our study, a hyaluronic acid (HA)-carboxymethyl chitosan (CMC) conjugate linked via a disulfide-bond (HA-SS-CMC, HSC) was synthesized to fabricate nanodroplets (NDs). The NDs encapsulating doxorubicin (DOX) and perfluorohexane (DOX-HSC-NDs) were prepared via a homogenization/emulsification strategy and exhibited not only high biocompatibility but also noticeable tumor cell targeting ability and dual pH/redox responsiveness. Besides, DOX-HSC-NDs can be used as a contrast-enhanced ultrasound imaging agent for specific tumor imaging. DOX-HSC-NDs in combination with ultrasound targeted microbubble destruction could improve intracellular drug aggregation and retention of MDR cells and work against multiple mechanisms of drug resistance through synergistic strategies, including up-regulating the reactive oxygen species (ROS) level, promoting apoptosis, and scavenging glutathione, while reducing the expression levels of P-glycoprotein and inhibiting the epithelial-mesenchymal transition. This combination strategy showed protective effects against TNBC in both MDA-MB-231/ADR cells and tumor-bearing mice. Our study for the first time developed and reported the ultrasound-augmented HSC-NDs as the DOX nanocarrier and provided scientific evidence to support the future application of DOX-HSC-NDs as a potential TNBC therapy.

Thymine-Modified Nanocarrier for Doxorubicin Delivery in Glioblastoma Cells.

Brain tumor glioblastoma is one of the worst types of cancer. The blood-brain barrier prevents drugs from reaching brain cells and shields glioblastoma from treatment. The creation of nanocarriers to improve drug delivery and internalization effectiveness may be the solution to this issue. In this paper, we report on a new nanocarrier that was developed to deliver the anticancer drug doxorubicin to glioblastoma cells. The nanocarrier was obtained by nanoemulsion polymerization of diallyl disulfide with 1-allylthymine. Diallyl disulfide is a redox-sensitive molecule involved in redox cell activities, and thymine is a uracil derivative and one of the well-known bioactive compounds that can enhance the pharmacological activity of doxorubicin. Doxorubicin was successfully introduced into the nanocarrier with a load capacity of about 4.6%. Biological studies showed that the doxorubicin nanocarrier composition is far more cytotoxic to glioblastoma cells (T98G) than it is to cancer cells (M-HeLa) and healthy cells (Chang liver). The nanocarrier improves the penetration of doxorubicin into T98G cells and accelerates the cells' demise, as is evident from flow cytometry and fluorescence microscopy data. The obtained nanocarrier, in our opinion, is a promising candidate for further research in glioblastoma therapy.

Carrier in carrier: Catanionic vesicles based on amphiphilic cyclodextrins complexed with DNA as nanocarriers of doxorubicin

• Catanionic vesicles (ModCBHD) derived from amphiphilic cyclodextrins were complexed with salmon sperm DNA. • DNA wraps around the vesicleś surface through electrostatic interactions, with conservation of structure of B-form. • ModCBHD-DNA-Dox system presents large stability, size around 200 nm, loading ability and release control of Doxorubicin. Doxorubicin (Dox) is a very effective chemotherapeutic agent; however, it can induce various side effects on normal tissues because of their non-specific distribution in the body. Therefore, there is an urgent demand to develop systems to successfully carry drugs to the desired sites of therapeutic action while reducing side effects. The aim of this study was to evaluate the interaction between catanionic vesicles based on amphiphilic cyclodextrins (ModCBHD) and DNA–Dox complex as a supramolecular anticancer drugs carrier (ModCBHD-DNA-Dox). The complexes were characterized by dynamic light scattering (DLS), zeta potential (ζ), circular dichroism (CD), emission spectroscopy, atomic force microscope (AFM), transmission electron microscopy (TEM). The results showed that ModCBHD vesicles exhibit a positive surface charge that allows negatively charged DNA-Dox to wrap them. Besides, Dox interacts with DNA through intercalation of the tetracene ring system and by ionic interaction through the amino sugar residue of the drug. In addition, ModCBHD-DNA-Dox exhibit a small particle size and optimal monodisperse size distribution that can take advantage of the enhanced permeability and retention (EPR) effect in cancer therapy. In vitro release of Dox from ModCBHD-DNA-Dox was slower than from DNA–Dox, due to the increasing appearance of external complexes formed from partially intercalated Dox after all the available sites become occupied upon addition of ModCBHD. The study overall highlighted a novel strategy that combine vesicles prepared from amphiphilic cyclodextrins and DNA that can be used as alternative carriers for chemotherapeutic agents such as Dox with slow-release properties.

Dual-modified starch micelles as a promising nanocarrier for doxorubicin

Natural amphiphilic polymer micelles have garnered considerable research attention as nanocarriers for delivering drugs. The objective of this study was to explore the possibility of applying biocompatible dual-modified starch micelles as drug delivery vehicles. To this end, a dual-modified corn starch polymer (SCD) was synthesized with zwitterionic sulfobetaine and deoxycholic acid; spherical micelles with an average particle size of ~200 nm were prepared through the self-assembly of SCD. The effects of dual modification on the degree of substitution, molecular structure, and functional properties of SCD were investigated. Further, doxorubicin was successfully incorporated into the micelles, and an in vitro drug release study was performed to confirm that the drug-loaded micelles displayed pH-sensitive properties with controlled and sustained release. The dissolve-diffuse-erosion-degradation release process was described according to the dynamic models of drug release for SCD micelles. The results can be used as reference information for further studies in the biotechnology and pharmaceutical domains.

Hybrid liposome/metal–organic framework as a promising dual-responsive nanocarriers for anticancer drug delivery

In this work, liposome-coated iron (III) benzene-1,3,5-tricarboxylate (Fe-BTC) metal–organic framework is examined as a promising pH/Ultrasound dual-responsive nanocarriers for doxorubicin (DOX) delivery. The successful coating of the MOF particles (Lip-Fe-BTC) with the phospholipid bilayer (PBL) was established by direct fusion into the synthesized liposomes. The liposome coating was verified using several techniques, including dynamic light scattering (DLS) and transmission electron microscopy (TEM). The DLS measurements showed an increase in the average particle diameter of liposomes from 150 nm to 163.1 nm for Lip-Fe-BTC particles. The Fe-BTC particles had the highest average particle diameter (287.3 nm). These results demonstrated that the PBL reduced the aggregation of the particles and improved their dispersity in the release medium. The TGA results demonstrated the MOF’s excellent thermal stability. Furthermore, the nanocarrier’s loading efficiency and capacity were determined to be ~90% and ~13.5 wt%, respectively. The in-vitro DOX release experiments demonstrated that the DOX-loaded Fe-BTC and liposome-coated Fe-BTC particles showed good pH and US dual-responsive capability, making them promising nanocarriers for drug delivery. The application of US enhanced DOX release from both Fe-BTC and liposome-coated Fe-BTC. In the case of Fe-BTC-DOX particles, the application of US enhanced the DOX release to around 38% and 67%, at pH levels of 7.4 and 5.3, respectively. Similarly, DOX release from the Lip-Fe-BTC-DOX particles reached ~35% and ~53%, at pH levels of 7.4 and 5.3, respectively. The MTT assay showed the biocompatibility and low cytotoxicity of these nanocarriers below 100 µg/ml.

Exploration of phosphorene as doxorubicin nanocarrier: An atomistic view from DFT calculations and MD simulations

Potential capability of phosphorene nanosheet (PNS) as doxorubicin (DOX) nanocarrier was investigated using density functional theory (DFT) method and molecular dynamics (MD) simulations. Both DFT calculations and MD simulations revealed that the DOX molecule is adsorbed horizontally onto the PNS surface with the nearest interaction distance of 2.5 Å. The binding energy of DOX is predicted to be about − 49.5 kcal.mol−1, based on the DFT calculations. After DOX adsorption, the Eg value of PNS remains almost constant in both gas and solvent phases. The dynamical behavior of PNS-DOX was studied at T = 298, 310, and 326 K that reminiscent of room temperature, body temperature, and temperature of tumor after exposure to 808 nm laser radiation, respectively. The diffusion coefficient values of DOX molecule are proportional to temperature. We found that PNS can hold a high amount of DOX on both sides of its surface (66% in weight). MD simulations showed that the dynamical behavior of simulated systems are not affected by pH variances.

A glutathione responsive nanocarrier based on viologen resorcinarene cavitand and 1-allylthymine

A glutathione-sensitive nanocarrier for doxorubicin to improve cellular penetration and selective cytotoxic effects on T98G human glioblastoma cells.

Folate-targeted doxorubicin delivery to breast and cervical cancer cells using a chitosan-gold nano-delivery system

Nanoparticles (NPs) are ideal candidates for safe, directed and effective delivery of chemotherapeutic agents to cancer cells. Herein, we report the synthesis of a gold NP (GNP) based delivery system as a platform for doxorubicin (DOX) delivery to cancer cells. GNPs synthesized by citrate reduction of the gold salt was used to encapsulate DOX, using sodium tripolyphosphate (TPP) as a linking agent. The subsequent functionalization of the DOX-GNP with chitosan (CS) and folate-linked chitosan (F-CS) resulted in the formation of CS-GNP-DOX and F-CS-GNP-DOX delivery systems. The synthesized DOX nanocarriers were characterized using UV–visible and ATR-FTIR spectroscopy, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Drug release and kinetic evaluations were done in simulated tumour and physiological microenviroments. The drug-nanocomplexes were evaluated in an in vitro MTT assay for their effect on cell proliferation with further assessments on the mechanisms associated with the toxicity. The NPs and nanocomplexes were spherically shaped, colloidally stable, and displayed a pH-dependent DOX release that closely followed a first or zero-order kinetic model. CS-GNP-DOX and F-CS-GNP-DOX displayed higher chemotherapeutic activity in the human breast (MCF-7), cervical (HeLa) and hepatocellular (HepG2) carcinoma cell lines when compared to free DOX. The lowest IC50 obtained for CS-GNP-DOX and F-CS-GNP-DOX in the cancer cells was significantly lower than that for free DOX. The F-CS-GNP-DOX nanocomplex displayed superior anticancer effects over CS-GNP-DOX in the breast and cervical cancer cells, predominantly due to enhanced cellular uptake via their over-expressed folate receptors (FRα). These nanocomplexes also induced mitochondrial membrane depolarization and activated downstream caspases during apoptotic induction in the breast and cervical cancer cells. Overall, these DOX-nanocomplexes have the potential for clinical application and are be promising lead candidates for further development.

An Efficient Carbon-Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway.

The emergence of nanocarriers solves the problems of antitumor drugs such as non-targeting, huge side effects, etc., and has been widely used in tumor therapy. Some kinds of antitumor drugs such as doxorubicin (DOX) mainly act on the nucleic acid causing DNA damage, interfering with transcription, and thereby disrupting or blocking the process of cancer cell replication. Herein, a new nanodrug delivery system, the carbon-based nanomaterials (CBNs)-Pluronic F127-DOX (CPD), is designed by using CBNs as a nanocarrier for DOX. As a result, the tumor growth inhibition rate of CPD group is as high as 79.42± 2.83%, and greatly reduces the side effects. The targeting rate of the CPD group of DOX in the tumor nucleus is 36.78%, and the %ID/g in tumor tissue is 30.09%. The CPD regulates the expression levels of Caspase-3, p53, and Bcl-2 genes by increasing intracellular reactive oxygen species (ROS) levels and reducing mitochondrial membrane potential, which indicates that mitochondrial-mediated pathways are involved in apoptosis. The CPD nanodrug delivery system increases the effective accumulation of DOX in tumor cell nuclei and tumor tissues, and generates massive ROS, thereby inhibiting tumor growth in vivo, representing a promising agent for anticancer applications.

Nuclear targeted multimodal 3D-bimetallic Au@Pd nanodendrites promote doxorubicin efficiency in breast cancer therapy

The therapeutic efficiency of doxorubicin (DOX) is dependent on its sufficient accumulation within the nucleus of cancer cells. Taking advantage of the fascinating properties (e.g., multiple dense arrays of hyperbranches and high surface area) of bimetallic nanodendrites as well as the arginine-rich components of protamine sulfate (PS), we herein present a new type of PS-modified [email protected] hydrophobic drug carrier in which DOX can effectively bind to the surface of the [email protected] nanocarrier via non-covalent attachment. Chemical characterization of the synthesized [email protected] showed the successful loading of DOX onto the surface of [email protected] Darkfield and Hyperspectral imaging analysis of the [email protected] demonstrated the time-dependent uptake and prolonged accumulation capability for releasing its DOX cargo inside the nucleus. Specifically, data from the 3D-CytoViva fluorescence imaging did not only track the nanocarrier’s distribution but also confirmed its predominant accumulation in the nuclear compartment through clathrin-mediated endocytosis. Cytotoxicity assay showed that the [email protected] significantly inhibited cancer cell proliferation with maximum DOX release under acidic conditions (pH 4.5 and 5.5) than at normal physiological pH of 7.4. Moreover, the resultant [email protected] DOX nanocarrier efficiently improved the induction of apoptosis in MCF-7 cells compared to free DOX and passive targeted platform. In addition, loss of membrane integrity, mitochondria-apoptotic pathway, and internucleosomal DNA contents from cell cycle progression assay provided insights on the mechanism of cell death. Overall, the [email protected] nanocarrier may be employed for improved subcellular delivery of DOX as well as multimodal visualization in cancer therapy.

Precise Controlled Target Molecule Release through Light-Triggered Charge Reversal Bridged Polysilsesquioxane Nanoparticles.

Precise control of target molecule release time, site, and dosage remains a challenge in controlled release systems. We employed a photoresponsive molecule release system via light-triggered charge reversal nanoparticles to achieve a triggered, stepwise, and precise controlled release platform. This release system was based on photocleavage-bridged polysilsesquioxane nanoparticles which acted as nanocarriers of doxorubicin loaded on the surface via electrostatic interaction. The nanoparticles could reverse into positive charges triggered by 254 nm light irradiation due to the photocleavage of the o-nitrobenzyl bridged segment. The charge reversal property of the nanoparticles could release loaded molecules. Doxorubicin was selected as a positively charged model molecule. The as-prepared nanoparticles with an average size of 124 nm had an acceptable doxorubicin loading content up to 12.8%. The surface charge of the nanoparticles could rapidly reverse from negative (−28.20 mV) to positive (+18.9 mV) upon light irradiation for only 10 min. In vitro release experiments showed a cumulative release up to 96% with continuously enhancing irradiation intensity. By regulating irradiation parameters, precisely controlled drug release was carried out. The typical “stepped” profile could be accurately controlled in an on/off irradiation mode. This approach provides an ideal light-triggered molecule release system for location, timing, and dosage. This updated controlled release system, triggered by near-infrared or infrared light, will have greater potential applications in biomedical technology.

Polymeric Nanocarriers: A Transformation in Doxorubicin Therapies.

Doxorubicin, a member of the anthracycline family, is a common anticancer agent often used as a first line treatment for the wide spectrum of cancers. Doxorubicin-based chemotherapy, although effective, is associated with serious side effects, such as irreversible cardiotoxicity or nephrotoxicity. Those often life-threatening adverse risks, responsible for the elongation of the patients’ recuperation period and increasing medical expenses, have prompted the need for creating novel and safer drug delivery systems. Among many proposed concepts, polymeric nanocarriers are shown to be a promising approach, allowing for controlled and selective drug delivery, simultaneously enhancing its activity towards cancerous cells and reducing toxic effects on healthy tissues. This article is a chronological examination of the history of the work progress on polymeric nanostructures, designed as efficient doxorubicin nanocarriers, with the emphasis on the main achievements of 2010–2020. Numerous publications have been reviewed to provide an essential summation of the nanopolymer types and their essential properties, mechanisms towards efficient drug delivery, as well as active targeting stimuli-responsive strategies that are currently utilized in the doxorubicin transportation field.

Redox and pH dual sensitive folate-modified star-like amphiphilic copolymer based on castor oil for controlled doxorubicin delivery

To overcome the problems associated with the use of doxorubicin (DOX), such as low solubility, high toxicity, and side effects, a redox and pH-sensitive drug delivery system based on a star-like copolymer of folate-modified poly (ethylene glycol) (PEG) and biodegradable castor oil was developed. Redox-sensitive disulfide linkage and pH-sensitive imine linkage were incorporated in the backbone of the star-like copolymer, which self-assembled into stable micelles with small particle size (91.67 nm), narrow size distribution, and low CMC value (2.7 mg/L). The disassembly behaviors of the micelles when exposed to endolysosomal pH of 5.5 and a high concentration of GSH were evaluated by scanning electron microscope from the changes of micellar morphology.The micelles were used to load DOX into the hydrophobic core. Drug loading capacity (DLC) and drug loading efficiency (DLE) were calculated to be 15.93% and 96.13%, respectively. In vitro release studies showed that DOX release from micelles followed a redox and pH-triggered manner. The introduction of dual trigger further expedited DOX release.In vitro cytotoxicity of the copolymer against HDF cells was investigated. The star-like copolymer showed no toxicity. While the DOX-loaded micelles suggested enhanced cytotoxicity against HeLa cells. These results indicated that these redox and pH-sensitive micelles have the potential as a nanocarrier for DOX and other hydrophobic anti-cancer drugs.

Hydrophilic Polyhedral Oligomeric Silsesquioxane, POSS(OH)32, as a Complexing Nanocarrier for Doxorubicin and Daunorubicin.

A novel strategy, recently developed by us, to use polyhedral oligomeric silsesquioxanes (POSS) as an anti-cancer drug carrier is presented. Anthracycline:POSS complexes were prepared by simple co-addition of doxorubicin (DOX) or daunorubicin (DAU) with hydrophilic POSS(OH)32. Co-delivery of POSS and anthracyclines led to higher anti-cancer activity towards HeLa (cervical cancer endothelial) and MCF-7 (human breast adenocarcinoma) cell lines. The obtained supramolecular hybrid complexes were characterised by nuclear magnetic resonance (NMR) spectroscopy (nuclear Overhauser effect spectroscopy [NOESY] and homonuclear correlation spectroscopy [COSY]), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The two-dimensional (2D) NOESY spectra of the complexes showed the cross-correlation peaks for hydroxyl groups of POSS (~4.3–4.8 ppm) with OH groups of DOX and DAU. FTIR showed that hydroxyl group of POSS can interact with amine and hydroxyl groups of DOX and DAU. The viability of HeLa and MCF-7 was analysed with the MTT assay to evaluate the cytotoxicity of free DOX and DAU and the relevant complexes with POSS at different molar ratios. At a low DOX concentration (2.5 µM), for molar ratios 1:1, 1:4, and 1:8 (POSS:DOX), the complexes showed two and three times higher cytotoxicity towards HeLa and MCF-7 cells, respectively, than DOX itself after both 24- and 48-h incubation. The 1 µM concentration for a 1:4 POSS:DOX molecular ratio and the 2.5 µM concentration for all complexes were more toxic towards MCF-7 cells than free DOX after 48-h incubation. In the case of POSS:DAU complexes, there was higher toxicity than that of free drug after 48-h incubation. It can be concluded that the formation of non-covalent complexes increases toxicity of anthracycline drugs towards Hela and MCF-7 cells. The novel complexes are inexpensive to prepare and more effective than free drugs at low systemic toxicity.

Preparation, characterization, and in-vitro studies of doxorubicin-encapsulated silica coated iron oxide nanocomposites on liver cancer cells

This research aims at the synthesis and characterization of silica modified magnetic iron oxide (IONP-SiO2) nanocomposites through a hydrothermal method. These nanocomposites will function as nanocarriers for doxorubicin (DOX) drug delivery system towards liver cancer therapy. Core–shells of monodispersed, spherical shaped, and nanosized nanocomposites were determined using the transmission electron microscopy. In addition, the X-ray powder diffraction patterns indicated the crystallization of the as-synthetized nanocomposites with diffraction peak at 2θ = 35.44° consistent to that of Fe3O4 (311). The XANES spectra of the iron atom in various samples demonstrated an absorbance feature (Fe = 7112 eV) of a 1 s to 3d transition. The characteristic bands between 1625, 1091, and 460 cm−1 are corresponding to the stretching vibration bends of Si-O bonds, indicating an effective coating of SiO2 on the surface of IONPs. The cell cytotoxicity tests indicated that there were no considerable cell toxicities observed among the Huh 7 and HepG2 liver cancer cells incubated using various concentrations of IONPs and IONP-SIO2. Interestingly, cell viability tests showed that after DOX encapsulation, the IONP-SIO2-DOX complex was able to induce more cell apoptosis or necrosis. This study presents an interdisciplinary work to create a new formulation of DOX delivery in liver cancer therapy with consequential advanced treatment. The IONP-SiO2 based drug delivery mechanism would be a possible mechanism to enhancing targeted delivery of conventional chemotherapeutic drugs and MRI imaging.