Abstract: Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC50 values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.
Abstract: Various nanomaterials can be used as a drug delivery
vehicles in nanomedicine, called nanocarriers. They can either be
organic or inorganic, synthetic or natural-based. Although synthetic
nanocarriers are easier to produce, they can often be toxic for the
organism and thus not suitable for use in treatment. From naturalbased
nanocarriers, the most commonly used are protein cages or
viral capsids. In this work, virus bacteriophage λ was used for
delivery of different cytotoxic drugs (cisplatin, carboplatin,
oxaliplatin and doxorubicin). Large quantities of phage λ were
obtained from phage λ-producing strain of E. coli cultivated in
medium with 0.2% maltose. After killing of E. coli with chloroform
and its removal by centrifugation, the phage was concentrated by
ultracentrifugation at 130 000×g and 4°C for 3 h. The encapsulation
of the drugs was performed by infusion method and four different
concentrations of the drugs were encapsulated (200; 100; 50; 25
μg·mL-1). Free drug molecules were removed by filtration. The
encapsulation was verified using the absorbance for doxorubicin and
atomic absorption spectrometry for platinum cytostatics. The amount
of encapsulated drug linearly increased with the increasing
concentration of applied drug with the determination coefficient
R2=0.989 for doxorubicin; R2=0.967 for cisplatin; R2=0.989 for
carboplatin and R2=0.996 for oxaliplatin. The overall encapsulation
efficiency was calculated as 50% for doxorubicin; 8% for cisplatin;
6% for carboplatin and 10% for oxaliplatin.
Abstract: Cancer is still one of the serious diseases threatening
the lives of human beings. How to have an early diagnosis and
effective treatment for tumors is a very important issue. The animal
carcinoma model can provide a simulation tool for the studies of
pathogenesis, biological characteristics, and therapeutic effects.
Recently, drug delivery systems have been rapidly developed to
effectively improve the therapeutic effects. Liposome plays an
increasingly important role in clinical diagnosis and therapy for
delivering a pharmaceutic or contrast agent to the targeted sites.
Liposome can be absorbed and excreted by the human body, and is
well known that no harm to the human body. This study aimed to
compare the therapeutic effects between encapsulated (doxorubicin
liposomal, Lipodox) and un-encapsulated (doxorubicin, Dox)
anti-tumor drugs using magnetic resonance imaging (MRI).
Twenty-four New Zealand rabbits implanted with VX2 carcinoma at
left thighs were classified into three groups: control group (untreated),
Dox-treated group, and LipoDox-treated group, 8 rabbits for each
group. MRI scans were performed three days after tumor implantation.
A 1.5T GE Signa HDxt whole body MRI scanner with a high
resolution knee coil was used in this study. After a 3-plane localizer
scan was performed, three-dimensional (3D) fast spin echo (FSE)
T2-weighted Images (T2WI) was used for tumor volumetric
quantification. Afterwards, two-dimensional (2D) spoiled gradient
recalled echo (SPGR) dynamic contrast-enhanced (DCE) MRI was
used for tumor perfusion evaluation. DCE-MRI was designed to
acquire four baseline images, followed by contrast agent Gd-DOTA
injection through the ear vein of rabbit. A series of 32 images were
acquired to observe the signals change over time in the tumor and
muscle. The MRI scanning was scheduled on a weekly basis for a
period of four weeks to observe the tumor progression longitudinally.
The Dox and LipoDox treatments were prescribed 3 times in the first
week immediately after the first MRI scan; i.e. 3 days after VX2 tumor
implantation. ImageJ was used to quantitate tumor volume and time
course signal enhancement on DCE images. The changes of tumor size
showed that the growth of VX2 tumors was effectively inhibited for
both LipoDox-treated and Dox-treated groups. Furthermore, the tumor
volume of LipoDox-treated group was significantly lower than that of
Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is
significantly lower than that of the other two groups, which implies
that targeted therapeutic drug remained in the tumor tissue. This study
provides a radiation-free and non-invasive MRI method for
therapeutic monitoring of targeted liposome on an animal tumor
model.
Abstract: Doxorubicin (DOX) is an anthracycline drug used to treat many cancer diseases. Similarly to other cytostatic drugs, DOX has serious side effects; the biggest obstacle is the cardiotoxicity. With the aim of lowering the negative side effects and to target the DOX into the tumor tissue, the different nanoparticles (NPs) are studied. The aim of this work was to synthetized different NPs and conjugated them with DOX and determine the binding capacity of the NPs. For this experiment, carbon nanotubes (CNTs), graphene oxide (GO), fullerene (FUL) and liposomes (LIP) were used. The highest binding capacity was observed in GO (85%). Subsequently the toxicity of NPs and NPs-DOX conjugates was analyzed in in vivo system (chicken embryos). Some NPs (GO) can increase the toxicity of DOX, whereas other NPs (LIP, CNTs) decrease DOX toxicity.
Abstract: To ensure targeting of apoferritin nanocarrier with
encapsulated doxorubicin drug, we used a peptide linker based on a
protein G with N-terminus affinity towards Fc region of antibodies.
To connect the peptide to the surface of apoferritin, the C-terminus of
peptide was made of cysteine with affinity to gold. The surface of
apoferritin with encapsulated doxorubicin (APODOX) was coated
either with gold nanoparticles (APODOX-Nano) or gold(III) chloride
hydrate reduced with sodium borohydride (APODOX-HAu). The
reduction with sodium borohydride caused a loss of doxorubicin
fluorescent properties and probably accompanied with the loss of its
biological activity. Fluorescent properties of APODOX-Nano were
similar to the unmodified APODOX; therefore it was more suited for
the intended use. To evaluate the specificity of apoferritin modified
with antibodies, ELISA-like method was used with the surface of
microtitration plate wells coated by the antigen (goat anti-human IgG
antibodies). To these wells, the nanocarrier was applied. APODOX
without the modification showed 5× lower affinity to the antigen than
APODOX-Nano modified gold and targeting antibodies (human IgG
antibodies).
Abstract: Doxorubicin, also known as Adriamycin, is an
anthracycline class of drug used in cancer chemotherapy. It is used in
the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute
leukemia, breast cancer, lung cancer, endometrium cancer and ovary
cancers. It functions via intercalating DNA and ultimately killing
cancer cells. The major side effects of doxorubicin are hair loss,
myelosuppression, nausea & vomiting, oesophagitis, diarrhea, heart
damage and liver dysfunction. The minor modifications in the
structure of compound exhibit large variation in the biological
activity, has prompted us to carry out the synthesis of sulfonamide
derivatives. Sulfonamide is an important feature with broad spectrum
of biological activity such as antiviral, antifungal, diuretics, antiinflammatory,
antibacterial and anticancer activities. Structure of the
synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilinoethyl)
benzene sulfonamide confirmed by proton nuclear magnetic
resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools
to assure the position of all protons and hence stereochemistry of the
molecule. Further we have reported the binding potential of
synthesized sulfonamide analogues in comparison to doxorubicin
drug using Auto Dock 4.2 software. Computational binding energy
(B.E.) and inhibitory constant (Ki) has been evaluated for the
synthesized compound in comparison of doxorubicin against Poly
(dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences.
The in vitro cytotoxic study against human breast cancer cell lines
confirms the better anticancer activity of the synthesized compound
over currently in use anticancer drug doxorubicin. The IC50 value of
the synthesized compound is 7.12 μM whereas for doxorubicin is 7.2
μM.
Abstract: The nanotechnology offers some exciting possibilities in cancer treatment, including the possibility of destroying tumors with minimal damage to healthy tissue and organs by targeted drug delivery systems. Considerable achievements in investigations aimed at the use of ZnO nanoparticles and nanocontainers in diagnostics and antitumor therapy were described. However, there are substantial obstacles to the purposes to be achieved by the use of zinc oxide nanosize materials in antitumor therapy. Among the serious problems are the techniques of obtaining ZnO nanosize materials. The article presents a new vector delivery system for the known antitumor drug, doxorubicin in the form of polymeric (PEO, starch-NaCMC) hydrogels, in which nanosize ZnO film of a certain thickness are deposited directly on the drug surface on glass substrate by DC-magnetron sputtering of a zinc target. Anticancer activity in vitro and in vivo of those nanosize zinc oxide composites is shown.
Abstract: The paper presents a new drugs delivery system, based on the thin film technology. As a model antitumor drug, highly toxic doxorubicin is chosen. The system is based on the technology of obtaining zinc oxide composite of doxorubicin by deposition of nanosize ZnO films on the surface of doxorubicin coating on glass substrate using DC magnetron sputtering of zinc targets in Ar:O2 medium at room temperature. For doxorubicin zinc oxide compositions in the form of coatings and gels with 180-200nm thick ZnO films, higher (by a factor 2) in vivo (ascitic Ehrlich's carcinoma) antitumor activity is observed at low doses of doxorubicin in comparison with that of the initial preparation at therapeutic doses. The vector character of the doxorubicin zinc oxide composite transport to tumor tissues ensures the increase in antitumor activity as well as decrease of toxicity in comparison with the initial drug.
Abstract: The nanosized polymeric micelles release the drug
due to acoustic cavitation, which is enhanced in dual frequency
ultrasonic fields. In this study, adult female Balb/C mice were
transplanted with spontaneous breast adenocarcinoma tumors and
were injected with a dose of 1.3 mg/kg doxorubicin in one of three
forms: free doxorubicin, micellar doxorubicin without sonication and
micellar doxorubicin with sonication. To increase cavitation yield,
the tumor region was sonicated with low level dual frequency of 3
MHz and 28 kHz. The animals were sacrificed 24 h after injection,
and their tumor, heart, spleen, liver, kidneys and plasma were
separated and homogenized. The drug content in their tumor, heart,
spleen, liver, kidneys and plasma was determined using tissue
fluorimetry. The results show that in the group that received micellar
doxorubicin with sonication, the drug concentration in the tumor
tissue was nine and three times higher than in the free doxorubicin
group and the micellar doxorubicin without sonication group,
respectively. In the micellar doxorubicin with sonication group, the
drug concentration in other tissues was lower than other groups
(p
Abstract: Female breast cancer is the second in frequency after cervical cancer. Surgery is the most common treatment for breast cancer, followed by chemotherapy as a treatment of choice. Although effective, it causes serious side effects. Controlled-release drug delivery is an alternative method to improve the efficacy and safety of the treatment. It can release the dosage of drug between the minimum effect concentration (MEC) and minimum toxic concentration (MTC) within tumor tissue and reduce the damage of normal tissue and the side effect. Because an in vivo experiment of this system can be time-consuming and labor-intensive, a mathematical model is desired to study the effects of important parameters before the experiments are performed. Here, we describe a 3D mathematical model to predict the release of doxorubicin from pluronic gel to treat human breast cancer. This model can, ultimately, be used to effectively design the in vivo experiments.
Abstract: pH-sensitive drug targeting using nanoparticles for
cancer chemotherapy have been spotlighted in recent decades. Graft
copolymer composed of poly (L-histidine) (PHS) and dextran
(DexPHS) was synthesized and pH-sensitive nanoparticles were
fabricated for pH-responsive drug delivery of doxorubicin (DOX).
Nanoparticles of DexPHS showed pH-sensitive changes in particle
sizes and drug release behavior, i.e. particle sizes and drug release rate
were increased at acidic pH, indicating that DexPHS nanoparticles
have pH-sensitive drug delivery potentials. Antitumor activity of
DOX-incorporated DexPHS nanoparticles were studied using CT26
colorectal carcinoma cells. Results indicated that fluorescence
intensity was higher at acidic pH than basic pH. These results
indicated that DexPHS nanoparticles have pH-responsive drug
targeting.
Abstract: Since hyaluronic acid (HA) receptor such as CD44 is
over-expressed at sites of cancer cells, HA can be used as a targeting
vehicles for anti-cancer drugs. The aim of this study is to synthesize
block copolymer composed of hyaluronic acid and
poly(ε-caprolactone) (HAPCL) and to fabricate polymeric micelles for
anticancer drug targeting against CD44 receptor of tumor cells.
Chemical composition of HAPCL was confirmed using 1H NMR
spectroscopy. Doxorubicin (DOX) was incorporated into polymeric
micelles of HAPCL. The diameters of HAPHS polymeric micelles
were changed around 80nm and have spherical shapes. Targeting
potential was investigated using CD44-overexpressing. When
DOX-incorporated polymeric micelles was added to KB cells, they
revealed strong red fluorescence color while blocking of CD44
receptor by pretreatment of free HA resulted in reduced intensity,
indicating that HAPCL polymeric micelles have targetability against
CD44 receptor.
Abstract: This study determines the effect of naked and heparinbased
super-paramagnetic iron oxide nanoparticles on the human
cancer cell lines of A2780. Doxorubicin was used as the anticancer
drug, entrapped in the SPIO-NPs. This study aimed to decorate
nanoparticles with heparin, a molecular ligand for 'active' targeting
of cancerous cells and the application of modified-nanoparticles in
cancer treatment. The nanoparticles containing the anticancer drug
DOX were prepared by a solvent evaporation and emulsification
cross-linking method. The physicochemical properties of the
nanoparticles were characterized by various techniques, and uniform
nanoparticles with an average particle size of 110±15 nm with high
encapsulation efficiencies (EE) were obtained. Additionally, a
sustained release of DOX from the SPIO-NPs was successful.
Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell
toxicity than the individual HP and confocal microscopy analysis
confirmed excellent cellular uptake efficiency. These results indicate
that HP based SPIO-NPs have potential uses as anticancer drug
carriers and also have an enhanced anticancer effect.