Three musketeers of PDA-based MRI contrasting and therapy.

Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.

Oxidative Stress in Xenograft Mouse Model Exposed to Dendrimers Decorated Polydopamine Nanoparticles and Targeted Chemo- and Photothermal Therapy.

Polydopamine (PDA)-based nanostructures are used for biomedical purposes. A hybrid drug nanocarrier based on a PDA decorated with polyamidoamine (PAMAM) dendrimers G 3.0 (DG3) followed by a connection with glycol (PEG) moieties, folic acid (FA), and drug doxorubicin (DOX) was used for combined chemo- and photothermal therapy (CT-PTT) of liver cancer. Oxidative stress plays a crucial role in the development of cancer, and PDA seems to have the ability to both donate and accept electrons. We investigated oxidative stress in organs by evaluating oxidative stress markers in vivo. In the liver, the level of reduced glutathione (GSH) was lower and the level of Trolox equivalent antioxidant capacity (TEAC) was higher in the group receiving doxorubicin encapsulated in PDA nanoparticles with phototherapy (PDA@DG3@PEG@FA@DOX + PTT) compared to the control group. The concentration of thiobarbituric acid reactive substances (TBARS) in livers, was higher in the group receiving PDA coated with PAMAM dendrimers and functionalized with PEG and FA (PDA@DG3@PEG@FA) than in other groups. Markers in the brain also showed lower levels of GSH in the PDA@DG3@PEG@FA group than in the control group. Markers of oxidative stress indicated changes in the organs of animals receiving PDA nanoparticles with PAMAM dendrimers functionalized with FA in CT-PTT of liver cancer under in vivo conditions. Our work will provide insights into oxidative stress, which can be an indicator of the toxic potential of PDA nanoparticles and provide new strategies to improve existing therapies.

Biomimetic theranostic nanoparticles for effective anticancer therapy and MRI imaging.

Cancer remains a leading cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Nanoparticle-based drug delivery systems have garnered significant interest due to their multifunctionality, offering the potential to enhance cancer treatment efficacy and improve patient tolerability. Membrane-coated drug delivery systems hold great potential for enhancing the therapeutic outcome of nanoparticle-based anticancer therapies. In this study, we report the synthesis of multifunctional iron-functionalized mesoporous polydopamine nanoparticles (MPDAFe NPs). These nanoformulations demonstrate substantial potential for combining efficient drug delivery and magnetic resonance imaging (MRI) and showcase the advantages of biomimetic coating with tumor cell-derived membranes. This coating confers prolonged circulation and improved the targeting capabilities of the nanoparticles. Furthermore, comprehensive biosafety evaluations reveal negligible toxicity to normal cells, while the combined chemo- and phototherapy exhibited significant cytotoxicity towards cancer cells. Additionally, the photothermal effect evaluation highlights the enhanced cytotoxicity achieved through laser irradiation, showcasing the synergistic effects of the nanomaterials and photothermal therapy. Importantly, our chemotherapeutic effect evaluation demonstrates the superior efficacy of doxorubicin-loaded MPDAFe@Mem NPs (cancer cell membrane-coated MPDAFe NPs) in inhibiting cancer cell viability and proliferation, surpassing the potency of free doxorubicin. This study comprehensively investigates theranostic, membrane-coated drug delivery systems, underlining their potential to increase the efficacy of cancer treatment strategies. The multifunctional nature of the iron-functionalized polydopamine nanoparticles allows for efficient drug delivery and imaging capabilities, while the biomimetic coating enhances their biocompatibility and targeting ability. These findings contribute valuable insights towards the development of advanced nanomedicine for improved cancer therapeutics.

Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models.

Carbon nanotubes are increasingly used in nanomedicine and material chemistry research, mostly because of their small size over a large surface area. Due to their properties, they are very attractive candidates for use in medicine and as drug carriers, contrast agents, biological platforms, and so forth. Carbon nanotubes (CNTs) may affect many organs, directly or indirectly, so there is a need for toxic effects evaluation. The main mechanisms of toxicity include oxidative stress, inflammation, the ability to damage DNA and cell membrane, as well as necrosis and apoptosis. The research concerning CNTs focuses on different animal models, functionalization, ways of administration, concentrations, times of exposure, and a variety of properties, which have a significant effect on toxicity. The impact of pristine CNTs on toxicity in rodent models is being increasingly studied. However, it is immensely difficult to compare obtained results since there are no standardized tests. This review summarizes the toxicity issues of pristine CNTs in rodent models, as they are often the preferred model for human disease studies, in different organ systems, while considering the various factors that affect them. Regardless, the results showed that the majority of toxicological studies using rodent models revealed some toxic effects. Even with different properties, carbon nanotubes were able to generate inflammation, fibrosis, or biochemical changes in different organs. The problem is that there are only a small amount of long-term toxicity studies, which makes it impossible to obtain a good understanding of later effects. This article will give a greater overview of the situation on toxicity in many organs. It will allow researchers to look at the toxicity of carbon nanotubes in a broader context and help to identify studies that are missing to properly assess toxicity.

Polydopamine Films with 2D-like Layered Structure and High Mechanical Resilience.

Highly oriented, layered, and mechanically resilient films of polydopamine (PDA) have been synthesized from the air/water interface. The films show a unique layered structure, as shown by scanning and transmission electron studies (SEM/TEM) and X-ray diffraction analysis (XRD), which resemble that of 2D layered materials. The films exhibit a composition typical of PDA-based materials, as evidenced by X-ray photoelectron spectroscopy (XPS); moreover, the samples present the distinctive resonance modes of PDA-based nanomaterials in Raman and infrared spectroscopy (FTIR) experiments. The presence of highly ordinated 3-4 protomolecule stacking, taking place at the air/water interface, with a unique eumelanin-like supramolecular arrangement is presented. Moreover, the films show superior mechanical resilience with E = 13 ± 4 GPa and H = 0.21 ± 0.03 GPa, as revealed by nanoindentation experiments, making them highly resilient and easily transferable. Finally, the ordering induced by the interface opens many possibilities for further studies, including those regarding the supramolecular structure on PDA due to their similarity to 2D layered materials.

Electron Spin Relaxation Studies of Polydopamine Radicals.

We present a thoroughgoing electron paramagnetic resonance investigation of polydopamine (PDA) radicals using multiple electron paramagnetic resonance techniques at the W-band (94 GHz), electron nuclear double resonance at the Q-band (34 GHz), spin relaxation, and continuous wave measurements at the X-band (9 GHz). The analysis proves the existence of two distinct paramagnetic species in the PDA structure. One of the two radical species is characterized by a long spin-lattice T1 relaxation time equal to 46.9 ms at 5 K and is assigned to the radical center on oxygen. The obtained data revealed that the paramagnetic species exhibit different electron spin relaxation behaviors due to different couplings to local phonons, which confirm spatial distancing between two radical types. Our results shed new light on the radical structure of PDA, which is of great importance in the application of PDA in materials science and biomedicine and allows us to better understand the properties of these materials and predict their future applications.

Polyamidoamine Dendrimers Decorated Multifunctional Polydopamine Nanoparticles for Targeted Chemo- and Photothermal Therapy of Liver Cancer Model.

The development of multifunctional drug delivery systems combining two or more nanoparticle-mediated therapies for efficient cancer treatment is highly desired. To face this challenge, a photothermally active polydopamine (PDA) nanoparticle-based platform was designed for the loading of chemotherapeutic drug and targeting of cancer cells. PDA spheres were first functionalized with polyamidoamine (PAMAM) dendrimers followed by the conjugation with polyethylene glycol (PEG) moieties and folic acid (FA) targeting ligand. The anticancer drug doxorubicin (DOX) was then absorbed on the particle surface. We performed the physico-chemical characterization of this versatile material and we assessed further its possible application in chemo- and photothermal therapy using liver cancer cell model. These nanoparticles exhibited high near-infrared photothermal conversion efficacy and allowed for loading of the drug, which upon release in specifically targeted cancer cells suppressed their growth. Using cell proliferation, membrane damage, apoptosis, and oxidative stress assays we demonstrated high performance of this nanosystem in cancer cell death induction, providing a novel promising approach for cancer therapy.

Magnetic Nanoparticles as a Carrier of dsRNA for Gene Therapy.

Glioma belongs to the most aggressive and lethal types of cancer. Glioblastoma multiforme (GBM), the most common type of malignant gliomas, is characterized by a poor prognosis and remains practically incurable despite aggressive treatment such as surgery, radiotherapy, and chemotherapy. Brain tumor cells overexpress a number of proteins that play a crucial role in tumorigenesis and may be exploited as therapeutic targets. One such target can be an extracellular matrix glycoprotein-tenascin-C (TN-C). Downregulation of TN-C by RNA interference (RNAi) is a very promising strategy in cancer therapy. However, the successful delivery of naked double-stranded RNA (dsRNA) complementary to TN-C sequence (ATN-RNA) requires application of delivery vehicles that can efficiently overcome rapid degradation by nucleases and poor intracellular uptake. Here, we present a protocol for application of MNP@PEI as a carrier for ATN-RNA to GBM cells. The obtained complexes consisted of polyethyleneimine (PEI)-coated magnetic nanoparticles combined with the dsRNA show high efficiency in ATN-RNA delivery, resulting not only in significant TN-C expression level downregulation, but also impairing the tumor cells migration.

Influence of PDA Coating on the Structural, Optical and Surface Properties of ZnO Nanostructures.

Polydopamine (PDA) is a new biocompatible material, which has prospects in biomedical and sensor applications. Due to functional groups, it can host wide range of biomolecules. ZnO nanostructures are well known templates for optical sensors and biosensors. The combination of ZnO and PDA results in a change of optical properties of ZnO-PDA composites as a shift of photoluminescence (PL) peaks and PL quenching. However, to date, the effect of the PDA layer on fundamental properties of ZnO-PDA nanostructures has not been studied. The presented paper reports on optical and surface properties of novel ZnO-PDA nanocomposites. PDA layers were chemically synthesized on ZnO nanostructures from different solution concentrations of 0.3, 0.4, 0.5 and 0.7 mg/mL. Structure, electronic and optical properties were studied by SEM, Raman, FTIR, diffuse reflectance and photoluminescence methods. The Z-potential of the samples was evaluated in neutral pH (pH = 7.2). The response of the samples towards poly-l-lysine adsorption, as a model molecule, was studied by PL spectroscopy to evaluate the correlation between optical and surface properties. The role of the PDA concentration on fundamental properties was discussed.

Magnetite Nanoparticles and Spheres for Chemo- and Photothermal Therapy of Hepatocellular Carcinoma in vitro.

INTRODUCTION: We present a multimodal nanoplatforms for the treatment of hepatocellular carcinoma (HCC) in vitro. The nanoplatforms are based on polydopamine (PDA)-coated magnetite nanoparticles (NPs) and spheres (sMAG) with PAMAM dendrimers and functionalized with NHS-PEG-Mal (N-hydroxysuccinimide-polyethylene glycol-maleimide) linker, which allows their functionalization with a folic acid derivative. The nanomaterials bearing a folic acid-targeting moiety show high efficiency in killing cancer cells in the dual chemo- and photothermal therapy (CT-PTT) of the liver cancer cells in comparison to modalities performed separately. MATERIALS AND METHODS: All materials are characterized in detail with transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential and magnetic measurements. Also, photothermal properties were determined under irradiation of nanoparticles with laser beam of 2 W/cm2. The nontoxicity of nanoparticles with doxorubicin and without was checked by WST and LIVE/DEAD assay. Those tests were also used to evaluate materials bearing folic acid and anticancer drug in combined chemo- and photothermal therapy of HCC. Further, the generation of reactive oxygen species profile was also evaluated using flow cytometry test. RESULTS: Both NPs and sMAG showed high photothermal properties. Nevertheless, the higher photothermal response was found for magnetic spheres. Materials of concentration above 10 µg/mL reveal that their activity was comparable to free doxorubicin. It is worth highlighting that a functionalized magnetic sphere with DOXO more strongly affected the HepG2 cells than smaller functionalized nanoparticles with DOXO in the performed chemotherapy. This can be attributed to the larger size of particles and a different method of drug distribution. In the further stage, both materials were assessed in combined chemo- and photothermal therapy (CT-PTT) which revealed that magnetic spheres were also more effective in this modality than smaller nanoparticles. CONCLUSION: Here, we present two types of nanomaterials (nanoparticles and spheres) based on polydopamine and PAMAM dendrimers g.5.0 functionalized with NHS-PEG-Mal linker terminated with folic acid for in vitro hepatocellular carcinoma treatment. The obtained materials can serve as efficient agents for dual chemo- and photothermal therapy of HCC. We also proved that PDA-coated magnetic spheres were more efficient in therapies based on near-infrared irradiation because determined cell viabilities for those materials are lower than for the same concentrations of nanomaterials based on small magnetic nanoparticles.

Facile and Controllable Growth of ß-FeOOH Nanostructures on Polydopamine Spheres.

Polydopamine (PDA) has a wide range of applications in biomedicine due to its high biocompatibility and surface chemistry and because of the presence of many functional groups in it, enabling further modification. As a catechol-like material, it has chelation properties for various types of metal ions, including iron. Here, we developed a procedure that uses PDA as a template to grow iron structures ß-FeOOH directly on its surface. The innovative approach of this work relies on that these structures can be obtained in neutral conditions and selective iron-ion source. The influence of iron-ion source, environment, and solution concentration on the structure and amount of resulting material is presented. The growth has been characterized over time, taking into account their photothermal, magnetic, and colloidal stability properties. Moreover, we shed new light on understanding the interaction of PDA with iron ions for the growth of iron-based nanostructure on polydopamine particles. Finally, we predict that PDA@ß-FeOOH nanoparticles could be a promising material in dual therapy merging photothermal therapy (PTT) treatment and magnetic resonance imaging (MRI) contrast agents.

Synthesis and photoluminescence properties of hybrid 1D core-shell structured nanocomposites based on ZnO/polydopamine.

In the present work, we report on the modelling of processes at the zinc oxide and polydopamine (ZnO/PDA) interface. The PDA layer was deposited onto ZnO nanorods (NRs) via chemical bath deposition. The defect concentrations in ZnO before and after PDA deposition were calculated and analysed. The ZnONRs/PDA core-shell nanostructures were studied by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman and Fourier-transform infrared (FTIR) spectroscopy, photoluminescence (PL) measurements, and diffuse reflectance spectroscopy. The TEM and electron energy loss spectroscopy (EELS) measurements confirmed the conformal coating of PDA, while the PL emission from ZnO and ZnONRs/PDA samples showed a reduction of intensity after the PDA deposition. The decrease of defect concentration participating in PL and quantum efficiency explains the PL reduction. Finally, the observed decrease of activation energies and a shift of the PL peaks are attributed to the formation of an additional local electrical field between the PDA and ZnO nanostructures.

NDs@PDA@ICG Conjugates for Photothermal Therapy of Glioblastoma Multiforme.

The growing incidence of cancer is a problem for modern medicine, since the therapeutic efficacy of applied modalities is still not satisfactory in terms of patients' survival rates, especially in the case of patients with brain tumors. The destructive influence of chemotherapy and radiotherapy on healthy cells reduces the chances of full recovery. With the development of nanotechnology, new ideas on cancer therapy, including brain tumors, have emerged. Photothermal therapy (PTT) is one of these. It utilizes nanoparticles (NPs) that can convert the light, preferably in the near-infrared (NIR) region, into heat. In this paper, we report the use of nanodiamonds (NDs) conjugated with biomimetic polydopamine (PDA) and indocyanine green (ICG) for glioblastoma cancer PTT therapy. The obtained materials were thoroughly analyzed in terms of their PTT effectiveness, as well as their physicochemical properties. The performed research demonstrated that NDs@PDA@ICG can be successfully applied in the photothermal therapy of glioblastoma for PTT and exhibited high photothermal conversion efficiency η above 40%, which is almost 10 times higher than in case of bare NDs. In regard to our results, our material was found to lead to a better therapeutic outcome and higher eradication of glioblastoma cells, as demonstrated in vitro.

The Effect of Tissue-Mimicking Phantom Compressibility on Magnetic Hyperthermia.

During hyperthermia, magnetite nanoparticles placed in an AC magnetic field become a source of heat. It has been shown that in fluid suspensions, magnetic particles move freely and generate heat easily. However, in tissues of different mechanical properties, nanoparticle movement is limited and leads to a small temperature rise in tissue. Therefore, it is crucial to conduct magnetic hyperthermia experiments in similar conditions to the human body. The effect of tissue-mimicking phantom compressibility on the effectiveness of magnetic hyperthermia was investigated on agar phantoms. Single and cluster nanoparticles were synthesized and used as magnetic materials. The prepared magnetic materials were characterized by transmission electron microscopy (TEM), and zeta potential measurements. Results show that tissue-mimicking phantom compressibility decreases with the concentration of agar. Moreover, the lower the compressibility, the lower the thermal effect of magnetic hyperthermia. Specific absorption rate (SAR) values also proved our assumption that tissue-mimicking phantom compressibility affects magnetic losses in the alternating magnetic field (AMF).

Nano-mediated delivery of double-stranded RNA for gene therapy of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common type of malignant gliomas, characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fueled a search for new therapeutic targets and treatment modalities. Here we report new approach towards RNA interference therapy of glioblastoma multiforme based on the magnetic nanoparticles delivery of the double-stranded RNA (dsRNA) with homological sequences to mRNA of tenascin-C (TN-C), named ATN-RNA. The obtained nanocomposite consisted of polyethyleneimine (PEI) coated magnetic nanoparticles conjugated to the dsRNA show high efficiency in ATN-RNA delivery, resulting not only in significant TN-C expression level suppressesion, but also impairing the tumor cells migration. Moreover, synthesized nanomaterials show high contrast properties in magnetic resonance imaging (MRI) and low cytotoxicity combining with lack of induction of interferon response. We believe that the present work is a successful combination of effective, functional, non-immunostimulatory dsRNA delivery system based on magnetic nanoparticles with high potential for further application in GBM therapy.

Dendrimer based theranostic nanostructures for combined chemo- and photothermal therapy of liver cancer cells in vitro.

Here we report the synthesis of multifunctional nanocarriers based on PAMAM dendrimers generation (G) 4.0, 5.0 and 6.0 fixed to polydopamine (PDA) coated magnetite nanoparticles (Fe3O4). Synthesized nanoplatforms were characterized by transmission electron microscopy (TEM), the electrokinetic (zeta) potential, Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and magnetic resonance imaging (MRI). Further, we show as a proof of concept that nanocarriers functionalized with G 5.0 could be successfully applied in combined chemo- and photothermal therapy (CT-PTT) of the liver cancer cells. The cooperative effect of the modalities mentioned above led to higher mortality of cancer cells when compared to their individual performance. Moreover, the performed in vitro studies revealed that the application of dual therapy triggered the desired cell death mechanism-apoptosis. Furthermore, performed tests using Magnetic Resonance Imaging (MRI) showed that our materials have competitive contrast properties. Overall, the functionality of dendrimers has been extended by merging them with magnetic nanoparticles resulting in multifunctional hybrid nanostructures that are promising smart drug delivery system for cancer therapy.

Anchoring Fe3O4 nanoparticles in a reduced graphene oxide aerogel matrix via polydopamine coating.

Reduced graphene oxide-magnetite hybrid aerogels attract great interest thanks to their potential applications, e.g., as magnetic actuators. However, the tendency of magnetite particles to migrate within the matrix and, ultimately, escape from the aerogel structure, remains a technological challenge. In this article we show that coating magnetite particles with polydopamine anchors them on graphene oxide defects, immobilizing the particles in the matrix and, at the same time, improving the aerogel structure. Polydopamine coating does not affect the magnetic properties of magnetite particles, making the fabricated materials promising for industrial applications.

Cyclodextrin-Based Magnetic Nanoparticles for Cancer Therapy.

Polydopamine (PDA)-coated magnetic nanoparticles functionalized with mono-6-thio-ß-cyclodextrin (SH-ßCD) were obtained and characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear and Magnetic Resonance Imaging (NMR and MRI), and doxorubicin (DOXO)-loading experiments. The liver cancer cellular internalization of DOXO-loaded nanoparticles was investigated by confocal imaging microscopy. Synthesized nanomaterials bearing a chemotherapeutic drug and a layer of polydopamine capable of absorbing near-infrared light show high performance in the combined chemo- and photothermal therapy (CT-PTT) of liver cancer due to the synergistic effect of both modalities as demonstrated in vitro. Moreover, our material exhibits improved T2 contrast properties, which have been verified using Carr-Purcell-Meiboom-Gill pulse sequence and MRI Spin-Echo imaging of the nanoparticles dispersed in the agarose gel phantoms. Therefore, the presented results cast new light on the preparation of polydopamine-based magnetic theranostic nanomaterials, as well as on the proper methodology for investigation of magnetic nanoparticles in high field MRI experiments. The prepared material is a robust theranostic nanoasystem with great potential in nanomedicine.

1st Symposium on Polydopamine and NanoTech Poland 2018: Conference Report.

The NanoTech Poland is an annual international conference with a strong scientific agenda focused on nanotechnology in energy, environment, and biomedicine. The Nanotech Poland 2018 was held at the NanoBioMedical Centre and Department of Physics at Adam Mickiewicz University in Poznan from June 6th to June 9th. The aim of NanoTech Poland 2018 was to bring together the scientific community's principal investigators, scientists, researchers, analysts, clinicians, policy makers, industry experts, and well-established and budding entrepreneurs to discuss the present and future perspectives in nanotechnology and nanoscience research and development. This year, the 1st Symposium on Polydopamine was held on June 6th. This forum was dedicated to the application of polydopamine and related catechol materials in a variety of research fields, both at the nano- and macroscale. The symposium gathered leading scientists from this important research field from top universities and institutions that have been involved in the research revolved around polydopamine. With over 200 national and international participants, NanoTech Poland 2018 and the 1st Symposium on Polydopamine provided a forum to present and discuss the latest scientific news from the field of nanotechnology with a strong interdisciplinary aspect and bioinspired materials.

Polydopamine-Based Multifunctional (Nano)materials for Cancer Therapy.

Since Lee published a pioneering paper about polydopamine (PDA), application of that polymer in a number of areas has grown enormously in the last 10 years and is still growing. PDA's spectacular success can be attributed to its unique features, i.e., simple preparation protocol, strong adhesive properties, easy and straightforward functionalization, and biocompatibility. Therefore, this polymer has attracted the attention of a vast group of scientists, including those working in the field of nanomedicine. In consequence, polydopamine has been merged with various nanostructures that differ in size and nature, which has resulted in novel types of multifunctional nanomaterials that have recently been extensively exploited in nanomedicine and particularly in cancer therapy. The aim of this article is to offer insight into the latest achievements (up until the end of 2016) in the field of synthesis and application of nanomaterials based on polydopamine and their application in cancer therapy. The conclusions regarding the application of polydopamine-based nanoplatforms in this area and future prospects are given at the end.