Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magnetic nanoparticles on pancreatic cancer and stellate cell lines

Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug delivery systems are a promising alternative to overcome the limitations of classical chemotherapies. The aim of this study is to obtain an effective targeted delivery system for gemcitabine using magnetic nanoparticles (MNPs) and all-trans retinoic acid (ATRA). This dual approach targets the tumor cells and its infrastructure – stellate cells – simultaneously. Gemcitabine and ATRA were loaded onto the PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs), which were synthesized and characterized previously. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Gemcitabine and ATRA loaded MNPs are efficiently taken up by pancreatic cancer and stellate cells successfully targeting and eliminating both cells. Results of this study can provide new insights on pancreatic cancer therapy where tumor is seen as a system with its stroma insead of epithelial cells alone.     

CpG oligodeoxynucleotide-loaded PAMAM dendrimer-coated magnetic nanoparticles promote apoptosis in breast cancer cells

One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which can generate a signal cascade for cell death. In our study, we utilized three-layer magnetic nanoparticles composed of a Fe₃O₄ magnetic core, an aminosilane (APTS) interlayer and a cationic poly(amidoamine) (PAMAM) dendrimer. This will be a novel targeted delivery system to enhance the accumulation of CpG-ODN molecules in tumor cells. The validation of CpG-ODN binding to DcMNPs was performed using agarose gel electrophoresis, UV-spectrophotometer, XPS analyses. Cytotoxicity of conjugates was assessed in MDA-MB231 and SKBR3 cancer cells based on cell viability by XTT assay and flow cytometric analysis. Our results indicated that the synthesized DcMNPs having high positive charges on their surface could attach to CpG-ODN molecules via electrostatic means. These nanoparticles with the average sizes of 40 ± 10 nm bind to CpG-ODN molecules efficiently and induce cell death in MDA-MB231 and SKBR3 tumor cells and could be considered a suitable targeted delivery system for CpG-ODN in biomedical applications. The magnetic core of these nanoparticles represents a promising option for selective drug targeting as they can be concentrated and held in position by means of an external magnetic field.     

Adsorption and desorption of chemotherapeutic drugs from a magnetically targeted carrier (MTC).

Magnetically targeted carriers (MTCs) are composite microparticles made from metallic iron and activated carbon. Particles, loaded with doxorubicin in the pharmacy (MTC-DOX), are infused intra-arterially through the artery feeding the tumor. With the aid of an externally positioned permanent dipole magnet, they can be localized and retained within a tumor mass. MTC-DOX is currently in use in a Phase I/II clinical study as a delivery vehicle for doxorubicin in primary hepatocellular carcinoma. The adsorption and desorption of doxorubicin, mitomycin C, camptothecin, methotrexate, verapamil and 9AC onto MTCs have been analyzed. Each of these chemotherapeutic agents has a different mechanism of action, suggesting that some benefit may be derived from combined delivery to a tumor using MTCs and magnetic targeting. Each drug displays different behavior with respect to adsorption and desorption. However, this behavior can be described for each drug with a non-linear thermodynamic model. The thermodynamic model predicts a controlled release rate by adjusting a number of parameters, including initial drug loading concentrations. This is confirmed with in vitro extraction experiments using human plasma as the extraction medium.     

Reversal of doxorubicin-resistance by multifunctional nanoparticles in MCF-7/ADR cells

The efficacy of many chemotherapeutic agents is reduced in cells that have developed multiple drug resistance (MDR). To address this important problem, a biodegradable polymer was coupled to a photosensitizer and the resulting photosensitizer-nanoparticles were loaded with the chemotherapeutic agent doxorubicin. The combination of photosensitizer and chemotherapeutic agent had a synergistic action on a doxorubicin-resistant breast cancer MCF-7 cell line. To increase the effectiveness of this combination, d-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS), an inhibitor of the multidrug transporter overproduced in these resistant cells, was added during the formation of the nanoparticles. The insertion of TPGS decreased the P-glycoprotein activity, increased the intracellular accumulation doxorubicin, and also increased the therapeutic efficacy of the resulting nanoparticles. Both TPGS and irradiation of the photoreactive nanoparticles caused doxorubicin to move from the cytoplasm to the nucleus. This combination of photodynamic activity in a powerful nanocarrier loaded with the chemotherapeutic agent doxorubicin can be used to deliver two types of cancer therapy simultaneously, and the addition of TPGS can further enhance the entry of doxorubicin into the nucleus. Therefore, this innovative delivery system can act as a potential nanomedicine for both drug-sensitive and drug-resistant cancer therapy.     

Simultaneous delivery of doxorubicin and GG918 (Elacridar) by new polymer-lipid hybrid nanoparticles (PLN) for enhanced treatment of multidrug-resistant breast cancer.

Multidrug-resistant (MDR) cancer may be treated using combinations of encapsulated cytotoxic drugs and chemosensitizers. To optimize for the effectiveness of this combinational approach, novel polymer-lipid hybrid nanoparticle (PLN) formulations capable of delivering a cytotoxic drug, doxorubicin (Dox), a chemosensitizer, GG918, or their combination were prepared. Both acute and long-term anticancer activities of various combinations of Dox and GG918 in solution or PLN form were evaluated in a human MDR breast cancer cell line (MDA435/LCC6/MDR1) using trypan blue exclusion and clonogenic assays. Cellular Dox uptake and drug distribution within the cells were determined by fluoremetry and fluorescence microscopy. The results showed that the encapsulation efficiencies of Dox and GG918 in PLN were up to 89% and were not compromised by co-encapsulation of the two agents. Of various combinational treatment approaches, the Dox and GG918 co-encapsulated PLN formulation ((DG)n) demonstrated the greatest Dox uptake and anticancer activity to the MDR cells, while co-administration of two single-agent loaded PLN was least effective. Fluorescence microscopy indicated cellular internalization of (DG)n. These findings suggest that in addition to the total drug concentrations, the simultaneous delivery of Dox and GG918 to the same cellular location is critical in determining the therapeutic effectiveness of this anticancer drug-chemosensitizer combination.     

Biocompatibility and biodistribution of suberoylanilide hydroxamic acid loaded poly (DL-lactide-co-glycolide) nanoparticles for targeted drug delivery in cancer

The biodegradable polymeric nanoparticles have been potentially used to carry various chemotherapy agents into cancer cells for targeted drug delivery. Conversely, the biodistribution and toxic effects of these drug-loaded nanoparticles have raised some concerns. In the present study, we tried to explore the prospective histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) loaded poly (DL-lactide-co-glycolide) (PLGA) nanoparticles biocompatibility and biodistribution in animal system. The biocompatibility of SAHA loaded PLGA nanoparticles were evaluated through hemolysis, biochemical and histopathological analysis. The analysis results showed SAHA loaded PLGA nanoparticles has good hemocompatibility, not at all an elevation of blood biochemical parameters and no specific remarkable tissues changes in liver, kidney, lung, and heart as compared with control. The orally administered SAHA loaded PLGA nanoparticles distributions in various organs were confirmed using spectrofluorometry and fluorescence microscope. The results shows nanoparticles were remained detectable in the liver, kidney, heart and lung tissues after 3 days. Moreover, the SAHA loaded PLGA nanoparticles are actively taken up in the A549 lung cancer cells. The overall results conclude that the histone deacetylase inhibitor SAHA loaded PLGA nanoparticles is biocompatible and actively distributed various organs in the animal system. The biocompatible SAHA loaded PLGA nanoparticles may be a suitable anticancer agent in the near feature.     

In-depth drug delivery to tumoral soft tissues via pH responsive hydrogel

A pH responsive nanoparticle–hydrogel hybrid drug delivery system was investigated for in-depth anticancer drug delivery to solid tumours. It consists of acid susceptible polymer nanoparticles loaded in a chitosan hydrogel. The hybrid formulation was characterized by UV-visible spectroscopy, FTIR, SEM, TEM, particle size analysis, zeta potential measurement and viscosity measurement. Drug encapsulation and nanoparticle loading efficiencies were found to be 48% and 72% respectively which describes the efficient interaction of the chemical entities in this hybrid drug delivery system. The hydrogel exhibited pH responsive behaviour: minimal drug and nanoparticle release at physiological pH but an increase in viscosity under acidic conditions and fast nanoparticle and drug release. The cytotoxicity of the drug loaded hydrogel was investigated against the MCF-7 breast cancer cell line along with the drug and nanoparticles without hydrogel. The drug loaded hydrogel showed a better cytotoxic effect on MCF-7 cancer cells. Thus, drug loaded nanoparticles containing hydrogel could be a better option for maximum drug distribution in tumours.

A pH responsive nanoparticle–hydrogel hybrid drug delivery system was investigated for in-depth anticancer drug delivery to solid tumours.     

Targeted drug release system based on pH-responsive PAA-POSS nanoparticles

An amphipathic PAA-POSS@DOX drug delivery system that responds sensitively to pH changes in the cancer microenvironment has been developed using a nanoparticle based on inorganic polyhedral oligomeric silsesquioxane (POSS). POSS was introduced to the carboxylic acid group of polyacrylic acid to which doxorubicin anticancer drug was loaded to prepare 480 ± 192 nm self-assembled nanoparticles. PAA-POSS had a high loading efficiency of over 75% and doxorubicin was quickly released to the target area responding sensitively to weakly acidic conditions. The possibility of employing PAA-POSS as a targeted drug delivery system has been confirmed by observing the death of cells of the MDA-MB-231 breast cancer line.

pH-sensitive PAA-POSS@DOX nanoparticles were synthesized and showed high loading efficiency of over 75% and doxorubicin was quickly released to the target area. The ability of PAA-POSS@DOX to kill MDA-MB-231 breast cancer cells has been demonstrated.     

Synthesis and efficacy of norfloxacin loaded onto magnetic hydrogel nanocomposites

A targeted drug delivery system based on biocompatible magnetic hydrogel nanocomposites consisting of poly[oligo(oxyethylene methacrylate)] anchored Fe₃O₄ nanoparticles was synthesized. The characteristics, thermal properties, morphology and magnetic properties were studied by XRD, FT-IR, TGA, SEM, TEM and VSM. A norfloxacin (NOR) anti-bacterial agent with a potential antitumor activity was immobilized into hydrogels, Fe₃O₄ nanoparticles and their magnetic hydrogel nanocomposites. The in vitro drug release manner of NOR was explored at different temperatures and pH values. The behavior of the drug release has been studied via different kinetic models. The antibacterial efficacy was tested against Streptococcus, Staphylococcus aureus, Kelebsella pneumonia and Escherichia coli via well diffusion method, and showed significant activity compared to the unloaded drug. Furthermore, an antitumor efficacy against HCT-116, HepG-2, PC3 and MCF-7 cancer cells revealed the highest cytotoxic efficacy with no influence on healthy cells. These nanodrugs, retaining both antibacterial and anticancer efficacy, have a talented therapeutic potential because of their selective cytotoxicity, connected with the ability to minimize the risk of bacterial infection in a cancer patient who is frequently immunocompromised.

A targeted drug delivery system based on biocompatible magnetic hydrogel nanocomposites consisting of poly[oligo(oxyethylene methacrylate)] anchored Fe₃O₄ nanoparticles was synthesized.     

Bacterial ghosts as novel advanced drug delivery systems: antiproliferative activity of loaded doxorubicin in human Caco-2 cells.

Systemic application of anticancer drugs often causes severe toxic side effects. To reduce the undesired effects, advanced drug delivery systems are needed which are based on specific cell targeting vehicles. In this study, bacterial ghosts from Mannheimia haemolytica were used for site-specific delivery of doxorubicin (DOX) to human colorectal adenocarcinoma cells (Caco-2). Bacterial ghosts are non-denatured envelopes of Gram-negative bacteria with fully intact surface structures for specific attachment to mammalian cells. The in vitro release profile of DOX-ghosts demonstrated that the loaded drug was non-covalently associated with the bacterial ghosts and that the drug delivery vehicles themselves represent a slow release system. Adherence studies showed that the M. haemolytica ghosts more efficiently than E. coli ghosts targeted the Caco-2 cells and released the loaded DOX within the cells. Cytotoxicity assays revealed that the DOX-ghosts exhibited potent antiproliferative activities on Caco-2 cells as the DOX associated with ghosts was two magnitude of orders more cytotoxic than free DOX provided in the medium at the same concentrations. Notably, a significant reduction in the cell viability was measured with DOX-ghosts at low DOX concentrations, which had no inhibitory effect when applied as free DOX after incubation for 16 h or when applied at higher concentrations for only 10 min to the cells. As the higher antiproliferative effects of DOX on Caco-2 cells were mediated by the specific drug targeting properties of the bacterial ghosts, the bacterial ghost system represents a novel platform for advanced drug delivery.     

HPMA copolymer-bound doxorubicin targeted to tumor-specific antigen of BCL1 mouse B cell leukemia.

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing the anticancer drug doxorubicin and targeted with B1 monoclonal antibody (mAb) to BCL1 leukemia cells was synthesised and tested in vitro and in vivo. BCL1 leukemia growing in syngenic Balb/c mice was selected as a tumor model system. B1 mAb recognising the idiotype of surface IgM on BCL1 cells was used as a targeting moiety. Both B1 mAb and doxorubicin were conjugated to HPMA copolymer carrier by aminolysis through a tetrapeptidic Gly-Phe(D,L)-Leu-Gly spacer to ensure the intracellular delivery and controlled release of the drug. B1 mAb-targeted conjugate was shown to possess strictly tumor-specific binding capacity to target BCL1 cells in vitro. A similar conjugate, but containing human nonspecific Ig (HuIg) instead of B1 mAb, failed to bind to BCL1 cells. In vitro, B1 mAb-targeted conjugate demonstrated 40-fold higher cytotoxic effect than nontargeted or human nonspecific Ig-containing HPMA copolymer-bound doxorubicin. Conjugate targeted with B1 mAb was also shown to bind to target BCL1 cells in vivo. B1 mAb-targeted conjugate was shown to be more efficient in the treatment of established BCL1 leukemia than free doxorubicin, nontargeted and human nonspecific Ig-containing conjugate. Antibody-targeted polymeric drugs are thus promising conjugates for cancer treatment.     

Targeted delivery of paclitaxel by functionalized selenium nanoparticles for anticancer therapy through ROS-mediated signaling pathways

As a therapeutic anticancer agent, the clinical use of paclitaxel (PTX) is limited by its poor water solubility and serious adverse side effects. The targeted-specific intracellular delivery of an anticancer drug as a new therapeutic modality is promising for cancer treatment. The anticancer activity of selenium nanoparticles (SeNPs) with low toxicity and excellent activity has attracted increasing attention for use in biomedical intervention in recent years. In this study, β-cyclodextrin (β-CD)-folate (FA)-modified selenium nanoparticles (SeNPs) loaded with paclitaxel (PTX) (Se@β-CD-FA@PTX) were successfully fabricated through a layer-by-layer method. The nanosystem is able to enter cancer cells through FA receptor-mediated endocytosis to achieve targeted-specific intracellular delivery. Se@β-CD-FA@PTX was found to increase the selectivity between normal and cancer cells. The viability in MCF-7 cells was remarkably lower than in MCF 10A cells, which may promote the specific targeted delivery of Se@β-CD-FA@PTX into MCF-7 cells. Moreover, Se@β-CD-FA@PTX was found to enhance the cytotoxic effect on MCF-7 cells via the induction of apoptosis activation of ROS-mediated p53 and AKT signaling pathways. The results demonstrate that Se@β-CD-FA@PTX nanoparticles provide a strategy for the design of cancer-targeted nanosystems for use in cancer therapy.

As a therapeutic anticancer agent, the clinical use of paclitaxel (PTX) is limited by its poor water solubility and serious adverse side effects.     

Surface design and preparation of multi-functional magnetic nanoparticles for cancer cell targeting,therapy, and imaging

Recently, theranostic candidates based on superparamagnetic iron oxide nanoparticles (SPIONs) providing the combination of therapy and diagnosis have become one of the most promising system in cancer research. However, poor stability, premature drug release, lack of specific tumor cell targeting, and complicated multi-step synthesis processes still hinder them for potential clinical applications. In this research, the multi-functional magnetic nanoparticles (MNPs-DOX) were prepared via a simple assembly process for targeted delivery of doxorubicin (DOX) and enhanced magnetic resonance (MR) imaging detection. Firstly, the multi-functional copolymer coating, polyamidoamine (PAMAM), was designed and synthesized by Michael addition reaction, where N,N-bis(acryloyl)cystamine served as backbone linker, and DOX, dopamine (DA), and polyethylene glycol (PEG) acted as comonomers. The PAMAM was then directly assembled to the surface of SPIONs by the ligand exchange reaction with SPIONs forming the MNPs-DOX. The hydrophilic PEG moieties provide the nanoparticles with colloidal stability and good-dispersity in aqueous solution. Comparing with the quick release of free DOX, the drug release behavior of MNPs-DOX exhibited a sustained drug release. Because the chemical cleavage of disulfide in the polymer backbone, a high cumulative drug release up to 60% in GSH within 48 h was observed, rather than only 26% in PBS (pH 7.4) without GSH. The MR imaging detection experiment showed that the MNPs-DOX had an enhanced T₂ relaxivity of 126 mM⁻¹ S⁻¹ for MR imaging. The results of the cytotoxicity assays showed a remarkable killing effect of cancer cells by MNPs-DOX due to the FA tumor-targeting ligand, comparing with non-targeted drug molecules. All the results showed that the as prepared multi-functional magnetic nanoparticles may serve as a promising theranostic candidate for targeted anticancer drug delivery and efficient detection through MR imaging in medical application.

Multi-functional magnetic nanoparticles for targeted anticancer drug delivery and efficient MR imaging detection in theranostics.     

Doxorubicin-loaded mesoporous magnetic nanoparticles to induce apoptosis in breast cancer cells

Selective targeting of chemotherapeutic drugs toward the cancer cells overcomes the limitations involved in chemotherapy. Ideally, targeted delivery system holds great potential in cancer therapy due to specific release of drug in the cancer tissues. In this regard, DOX-loaded chitosan coated mesoporous magnetic nanoparticles (DOX-CMMN) were prepared and evaluated for its physicochemical and biological characteristics. Nanosized magnetic nanoparticles were observed with a high loading capacity for DOX. The drug-loaded nanoparticles exhibited a controlled and sustained release of drug without any burst release phenomenon. The DOX-DMMN showed a concentration-dependent cell proliferation inhibitory action against breast cancer cells. The blank nanoparticles showed excellent biocompatibility with cell viability >85% at the maximum tested concentration. Our results showed that chitosan coated magnetic system has high potential for breast cancer targeting under an alternating current magnetic field (ACMF). The present study showed that magnetic nanoparticles can be targeted to tumor cells under the presence of oscillating magnetic field. The combined effect of chemotherapy and thermotherapy can have a promising clinical potential for the treatment of breast cancer.     

Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: implications for enhanced local drug delivery

Liquid perfluorocarbon nanoparticles serve as sensitive and specific targeted contrast and drug delivery vehicles by binding to specific cell surface markers. We hypothesized that application of acoustic energy at diagnostic power levels could promote nanoparticle-associated drug delivery by stimulating increased interaction between the nanoparticle's lipid layer and the targeted cell's plasma membrane. Ultrasound (mechanical index = 1.9) applied with a conventional ultrasound imaging system to nanoparticles targeted to alpha(v)beta3-integrins on C32 melanoma cancer cells in vitro produced no untoward effects. Within 5 min, lipid delivery from nanoparticles into cell cytoplasm was dramatically augmented. We also demonstrate the operation of a potential physical mechanism for this effect, the acoustic radiation force on the nanoparticles, which may contribute to the enhanced lipid delivery. Accordingly, we propose that local delivery of lipophilic substances (e.g., drugs) from targeted nanoparticles directly into cell cytoplasm can be augmented rapidly and safely with conventional ultrasound imaging devices through nondestructive mechanisms.     

Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin.

Angiogenesis is a key process in the growth and metastasis of a tumor. Disrupting this process is considered a promising treatment strategy. Therefore, a drug delivery system specifically aiming at angiogenic tumor endothelial cells was developed. Alpha v beta 3-integrins are overexpressed on actively proliferating endothelium and represent a possible target. For this, RGD-peptides with affinity for this integrin were coupled to the distal end of poly(ethylene glycol)-coated long-circulating liposomes (LCL) to obtain a stable long-circulating drug delivery system functioning as a platform for multivalent interaction with alpha v beta 3-integrins. The results show that cyclic RGD-peptide-modified LCL exhibited increased binding to endothelial cells in vitro. Moreover, intravital microscopy demonstrated a specific interaction of these liposomes with tumor vasculature, a characteristic not observed for LCL. RGD-LCL encapsulating doxorubicin inhibited tumor growth in a doxorubicin-insensitive murine C26 colon carcinoma model, whereas doxorubicin in LCL failed to decelerate tumor growth. In conclusion, coupling of RGD to LCL redirected these liposomes to angiogenic endothelial cells in vitro and in vivo. RGD-LCL containing doxorubicin showed superior efficacy over non-targeted LCL in inhibiting C26 doxorubicin-insensitive tumor outgrowth. Likely, these RGD-LCL-doxorubicin antitumor effects are brought about through direct effects on tumor endothelial cells.     

Chemotherapy of brain tumour using doxorubicin bound to surfactant-coated poly(butyl cyanoacrylate) nanoparticles: revisiting the role of surfactants.

Poly(butyl cyanoacrylate) nanoparticles coated with poloxamer 188 (Pluronic) F68) and also, as shown previously, polysorbate 80 (Tween 80) considerably enhance the anti-tumour effect of doxorubicin against an intracranial glioblastoma in rats. The investigation of plasma protein adsorption on the surface of the drug-loaded nanoparticles by two-dimensional electrophoresis (2-D PAGE) revealed that both surfactants, besides other plasma components, induced a considerable adsorption of apolipoprotein A-I (ApoA-I). It is hypothesized that delivery of doxorubicin to the brain by means of nanoparticles may be augmented by the interaction of apolipoprotein A-I that is anchored on the surface of the nanoparticles with the scavenger receptor class B type I (SR-BI) located at the blood-brain barrier. This is the first study that shows a correlation between the adsorption of apolipoprotein A-I on the nanoparticle surface and the delivery of the drug across the blood-brain barrier.     

Preparation and characterisation of rose Bengal-loaded surface-modified albumin nanoparticles.

Surface-modified albumin nanoparticles were prepared from two poly(ethylene glycol)-human serum albumin conjugates: poly(thioetheramido acid)-poly(ethylene glycol) copolymer-grafted HSA (HSA-PTAAC-PEG) and methoxy poly(ethylene glycol)-grafted HSA (HSA-mPEG). Rose bengal (RB) was used as a model drug for encapsulation into the nanoparticles either during the particle production or by adsorption post particle preparation. The drug incorporation and release was affected by the different production methods and the different polymer compositions. When RB was loaded in HSA and HSA/HSA-PTAAC-PEG nanoparticles, up to 5% (w/w) drug content was achieved. The drug loading in HSA-mPEG nanoparticles was much lower and the results from the microcalorimetry study indicated that the low loading efficiency was due to less drug-protein binding sites available in the HSA-mPEG molecule as compared to the HSA molecule. The release of RB from the albumin nanoparticles was very slow in PBS and dramatically accelerated in the presence of trypsin. Compared with unmodified nanoparticles, the slower release of RB from the surface-modified HSA nanoparticles in the presence of the enzyme suggested that the existence of a steric hydrophilic barrier on the surface of the nanoparticles made digestion of the nanoparticles more difficult.     

Idarubicin-loaded folic acid conjugated magnetic nanoparticles as a targetable drug delivery system for breast cancer

Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform–infrared spectroscopy (FT–IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0–500 μg/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy.     

Magnetically targeted co-delivery of hydrophilic and hydrophobic drugs with hollow mesoporous ferrite nanoparticles

A magnetically targeted drug delivery system (DDS) is developed to solve the delivery problem of hydrophobic drugs by using hollow mesoporous ferrite nanoparticles (HMFNs). The HMFNs are synthesized by a one-pot hydrothermal method based on the Ostwald ripening process. The biocompatibility of the synthesized HMFNs was determined by MTT assay, lactate dehydrogenase (LDH) leakage assay and hemolyticity against rabbit red blood cells. Moreover, Prussian blue staining and bio-TEM observations showed that the cell uptake of nanocarriers was in a dose and time-dependent manner, and the nanoparticles accumulate mostly in the cytoplasm. A typical highly hydrophobic anti-tuberculosis drug, rifampin (RFP) was loaded into HMFNs using supercritical carbon dioxide (SC-CO₂) impregnation, and the drug loading amount reached as high as 18.25 wt%. In addition, HMFNs could co-encapsulate and co-deliver hydrophobic (RFP) and hydrophilic (isoniazide, INH) drugs simultaneously. The in vitro release tests demonstrated extra sustained co-release profiles of rifampicin and isoniazide from HMFNs. Based on this novel design strategy, the co-delivery of drugs in the same carrier enables a drug delivery system with efficient enhanced chemotherapeutic effect.

A magnetically targeted drug delivery system (DDS) is developed to solve the delivery problem of hydrophobic drugs by using hollow mesoporous ferrite nanoparticles (HMFNs).