Core-size and geometry toxicity in small amino terminated PAMAM dendrimers.

A series of 6 small PAMAM dendrimers (G0-dendrimers) differing in the size, polarity and flexibility has been synthesized. The toxicity has been investigated in three different human cancer cell lines (HeLa, MCF-7, THP-1) and the endothelial skin cell line HMEC-1 in order to evaluate their potential as vehicles for drug delivery.

Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented.

Dendrimersomes: Biomedical applications.

In recent years, dendrimer-based vesicles, known as dendrimersomes, have garnered significant attention as highly promising alternatives to lipid vesicles in a variety of biomedical applications. Dendrimersomes offer several advantages, including relatively straightforward synthesis, non-immunogenic properties, stability in circulation, and minimal size variability. These vesicles are composed of Janus dendrimers, which are polymers characterized by two dendritic wedges with different terminal groups - hydrophilic and hydrophobic.

Advancing Antiamyloidogenic Activity by Fine-Tuning Macromolecular Topology.

Amyloid β peptide can aggregate into thin β-sheet fibrils or plaques deposited on the extracellular matrix, which is the hallmark of Alzheimer's disease. Multifunctional macromolecular structures play an important role in inhibiting the aggregate formation of amyloidogenic materials and thus are promising candidates with antiamyloidogenic characteristics for the development of next-generation therapeutics. In this study, we evaluate how small differences in the dendritic topology of these structures influence their antiamyloidogenic activity by the comparison of "perfectly dendritic" and "pseudodendritic" macromolecules, both decorated with mannose units.

Is acriflavine an efficient co-drug in chemotherapy?

Cancer is a global health problem being the second worldwide cause of deaths right after cardiovascular diseases. The main methods of cancer treatment involve surgery, radiation and chemotherapy with an emphasis on the latter. Thus development of nanochemistry and nanomedicine in a search for more effective and safer cancer treatment is an important area of current research.

Cross-linkable star-hyperbranched unimolecular micelles for the enhancement of the anticancer activity of clotrimazole.

Clotrimazole, a hydrophobic drug routinely used in the treatment of vaginal candidiasis, also shows antitumor activity. However, its use in chemotherapy has been unsuccessful to date due to its low solubility in aqueous media. In this work, new unimolecular micelles based on polyether star-hyperbranched carriers of clotrimazole are presented that can enhance solubility, and consequently the bioavailability, of clotrimazole in water.

Star-Shaped Poly(furfuryl glycidyl ether)-Block-Poly(glyceryl glycerol ether) as an Efficient Agent for the Enhancement of Nifuratel Solubility and for the Formation of Injectable and Self-Healable Hydrogel Platforms for the Gynaecological Therapies.

In this paper, we present novel well-defined unimolecular micelles constructed a on poly(furfuryl glycidyl ether) core and highly hydrophilic poly(glyceryl glycerol ether) shell, PFGE-b-PGGE. The copolymer was synthesized via anionic ring-opening polymerization of furfuryl glycidyl ether and (1,2-isopropylidene glyceryl) glycidyl ether, respectively. MTT assay revealed that the copolymer is non-cytotoxic against human cervical cancer endothelial (HeLa) cells.

Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy.

Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches.

Synthesis and Shaping of Core-Shell Tecto Dendrimers for Biomedical Applications.

In recent years, the use of poly(amidoamine) (PAMAM) dendrimers of different generations as building blocks or reactive modules to construct core-shell tecto dendrimers (CSTDs) that are superior to the performance of single-generation dendrimers has received great attention in the field of biomedical applications. The CSTDs are always based on high-generation dendrimers as the core and low-generation dendrimers as the shell; not only do they have excellent properties similar to single high-generation dendrimers, but they also have overcome some of the shortcomings (e.g.

Hydrophilic Polyhedral Oligomeric Silsesquioxane, POSS(OH), 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). 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.

Influence of Free Fatty Acids on Lipid Membrane-Nisin Interaction.

The influence of free fatty acids (FFAs) on the nisin-membrane interaction was investigated through micro-DSC and fluorescence spectroscopy. A simple but informative model membrane was prepared (5.7 DMPC:3.

In Search of a Phosphorus Dendrimer-Based Carrier of Rose Bengal: Tyramine Linker Limits Fluorescent and Phototoxic Properties of a Photosensitizer.

Photodynamic therapy (PDT) is a skin cancer treatment alternative to chemotherapy and radiotherapy. This method exploits three elements: a phototoxic compound (photosensitizer), light source and oxygen. Upon irradiation by light of a specific wavelength, the photosensitizer generates reactive oxygen species triggering the cascade of reactions leading to cell death.

Synthesis, Characterization, and Studies of an Reactive Oxygen Species (ROS)-Responsive Methoxy Polyethylene Glycol-Thioketal-Melphalan Prodrug for Glioblastoma Treatment.

Glioblastoma (GBM) is the most frequent and aggressive primary tumor of the brain and averages a life expectancy in diagnosed patients of only 15 months. Hence, more effective therapies against this malignancy are urgently needed. Several diseases, including cancer, are featured by high levels of reactive oxygen species (ROS), which are possible GBM hallmarks to target or benefit from.

Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Efficient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery.

The disruption of the cellular pathways of protein biosynthesis through the mechanism of RNA interference has been recognized as a tool of great diagnostic and therapeutic significance. However, in order to fully exploit the potential of this phenomenon, efficient and safe carriers capable of overcoming extra- and intracellular barriers and delivering siRNA to the target cells are needed. Recently, attention has focused on the possibility of the application of multifunctional nanoparticles, dendrimers, as potential delivery devices for siRNA.

Application of new lysine-based peptide dendrimers D3K2 and D3G2 for gene delivery: Specific cytotoxicity to cancer cells and transfection in vitro.

In order to enhance intracellular uptake and accumulation of therapeutic nucleic acids for improved gene therapy methods, numerous delivery vectors have been elaborated. Based on their origin, gene carriers are generally classified as viral or non-viral vectors. Due to their significantly reduced immunogenicity and highly optimized methods of synthesis, nanoparticles (especially those imitating natural biomolecules) constitute a promising alternative for virus-based delivery devices.

Multicomponent Conjugates of Anticancer Drugs and Monoclonal Antibody with PAMAM Dendrimers to Increase Efficacy of HER-2 Positive Breast Cancer Therapy.

Purpose: Conjugation of nanocarriers with antibodies that bind to specific membrane receptors that are overexpressed in cancer cells enables targeted delivery. In the present study, we developed and synthesised two PAMAM dendrimer-trastuzumab conjugates that carried docetaxel or paclitaxel, specifically targeted to cells which overexpressed HER-2.

Methods: The H NMR, C NMR, FTIR and RP-HPLC were used to analyse the characteristics of the products and assess their purity.

Molecular Mechanisms of Antitumor Activity of PAMAM Dendrimer Conjugates with Anticancer Drugs and a Monoclonal Antibody.

Taxanes are considered fundamental drugs in the treatment of breast cancer, but despite the similarities, docetaxel (doc) and paclitaxel (ptx) work differently. For this reason, it is interesting to identify mechanisms of antitumor activity of PAMAM dendrimer conjugates that carry docetaxel or paclitaxel and monoclonal antibody trastuzumab, specifically targeted to cells which overexpressed HER-2. For this purpose, the impact on the level of reactive oxygen species, the mitochondrial membrane potential, cell cycle distribution and the activity of caspases-3/7, -8 and -9 of PAMAM-doc-trastuzumab and PAMAM-ptx-trastuzumab conjugates was determined and compared with free docetaxel and paclitaxel toward HER-2-positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines.

Pyrrolidone-modified PAMAM dendrimers enhance anti-inflammatory potential of indomethacin in vitro.

The therapeutic effect of indomethacin, a water-insoluble non-steroidal anti-inflammatory drug, requires its efficient transport through cellular membranes and accumulation inside the target cells. The application of dendritic polymers has been proposed for the improvement of the drug's solubility and intracellular delivery. In this study we evaluated the anti-inflammatory potential of novel, highly-biocompatible 4-carbomethoxypyrrolidone-coated PAMAM dendrimers loaded with indomethacin.

Cytotoxicity of Dendrimers.

Drug delivery systems are molecular platforms in which an active compound is packed into or loaded on a biocompatible nanoparticle. Such a solution improves the activity of the applied drug or decreases its side effects. Dendrimers are promising molecular platforms for drug delivery due to their unique properties.

Sugar Modification Enhances Cytotoxic Activity of PAMAM-Doxorubicin Conjugate in Glucose-Deprived MCF-7 Cells - Possible Role of GLUT1 Transporter.

Purpose: In order to overcome the obstacles and side effects of classical chemotherapy, numerous studies have been performed to develop the treatment based on targeted transport of active compounds directly to the site of action. Since tumor cells are featured with intensified glucose metabolism, we set out to develop innovative, glucose-modified PAMAM dendrimer for the delivery of doxorubicin to breast cancer cells.

Methods: PAMAM-dox-glc conjugate was synthesized and characterized by H NMR, FT-IR, size and zeta potential measurements.

Intrinsic Fluorescence of PAMAM Dendrimers-Quenching Studies.

Intrinsic, non-traditional fluorescence of polyamidoamine (PAMAM) dendrimers that do not possess classical fluorophores has been attracting considerable interest for the last decade. Many hypotheses regarding the source of the fluorescence have appeared, but some of them are still disputable. In order to shed new light on the nature of the phenomenon, we applied quenchers that are normally used to study intrinsic fluorescence of proteins (i.

Fludarabine-Specific Molecular Interactions with Maltose-Modified Poly(propyleneimine) Dendrimer Enable Effective Cell Entry of the Active Drug Form: Comparison with Clofarabine.

Fludarabine is an anticancer antimetabolite essential for modern chemotherapy, but its efficacy is limited due to the complex pharmacokinetics. We demonstrated the potential use of maltose-modified poly(propyleneimine) dendrimer as drug delivery agent to improve the efficiency of therapy with fludarabine. In this study, we elaborated a novel synthesis technique for radioactively labeled fludarabine triphosphate to prove for the first time the direct ability of nucleotide-glycodendrimer complex to enter and kill leukemic cells, without the involvement of membrane nucleoside transporters and intracellular kinases.

Complexes of Indomethacin with 4-Carbomethoxy-pyrrolidone PAMAM Dendrimers Show Improved Anti-inflammatory Properties and Temperature-Dependent Binding and Release Profile.

COX-2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common treatment for chronic inflammatory diseases like arthritis and atherosclerosis. However, they are associated with severe side effects such as cardiovascular events or stomach bleeding, due to coinhibition of other enzymes (COX1) and off-target accumulation. PAMAM dendrimers can solubilize lipophilic drugs and increase their circulation time; furthermore, PAMAM dendrimers seem to have some accumulation in inflammatory sides.

Conjugate of PAMAM Dendrimer, Doxorubicin and Monoclonal Antibody-Trastuzumab: The New Approach of a Well-Known Strategy.

The strategy utilizing trastuzumab, a humanized monoclonal antibody against human epidermal growth receptor 2 (HER-2), as a therapeutic agent in HER-2 positive breast cancer therapy seems to have advantage over traditional chemotherapy, especially when given in combination with anticancer drugs. However, the effectiveness of single antibody or antibody conjugated with chemotherapeutics is still far from ideal. Antibody⁻dendrimer conjugates hold the potential to improve the targeting and release of active substance at the tumor site.