Polyamidoamine Dendrimer G3 Research Articles

Evaluation of the interaction of a guanylhydrazone derivative with cobalt ferrite nanoparticles and PAMAM electrochemical and UV/visible spectroscopic techniques

Nowadays, scientific research grows a lot around nanotechnology, which connects many areas of knowledge such as electrochemistry and magnetic nanoparticles (MNPs). The study of bioactive substances by electrochemical methods is already very conceptual, and the association of magnetic nanoparticles has emerged as a new bias of this technique. Here, we report the results of the interaction between the molecule LQM10, a derivative of guanylhydrazone, with nanocarriers: cobalt ferrite magnetic nanoparticles (CoFe2O4 MNPs) and polyamidoamine dendrimer (PAMAM), seeking to unite the characteristics of each nanocarrier to benefit LQM10. The electrochemical system was composed of 3 electrodes, Ag/AgCl/Cl− saturated (reference), platinum (auxiliary), and modified glassy carbon (GCE) (work) with CoFe2O4 MNPs alone and with PAMAM G3, in buffered medium pH 7.03 with or without a co-solvent (analytical grade ethanol). UV-visible spectroscopic studies were carried out in aqueous-ethanolic medium in different concentrations of PAMAM G3 and CoFe2O4 MNPs. The magnetic properties of CoFe2O4 MNPs and each nanocarriers were confirmed by vibrating sample magnetometer and by field effect calorimetry. LQM10, which has a redox profile in oxidative potentials, showed good interaction with all tested electrodes and revealed considerable values of formation constant (KF), highlighting the GCE modified with CoFe2O4 MNPs (KF = 1.92 × 106 L/mol) and PAMAM G3, corroborating with the results of UV-visible data (Kb = 7.60 × 105 L/mol). The generation of heat by magnetic hyperthermia of CoFe2O4 MNPs in the presence of PAMAM G3 and LQM10 was determined (SAR = 0.72 W/g). Therefore, we demonstrated the association of promising nanocarriers (PAMAM G3 and CoFe2O4 MNPs) with anticancer substances and their applicability as magnetic hyperthermia.

Synthesis and Different Effects of Biotinylated PAMAM G3 Dendrimer Substituted with Nimesulide in Human Normal Fibroblasts and Squamous Carcinoma Cells

Squamous cell carcinoma (SCC) remains a main cause of mortality in patients with neck and head cancers, with poor prognosis and increased prevalence despite of available therapies. Recent studies have identified a role of cyclooxygenases, particularly inducible isoform cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2) in cancer cell proliferation, and its inhibition become a target for control of cancer development, particularly in the view of recognized additive or synergic action of COX-2 inhibitors with other forms of therapy. Nimesulide (N), the selective COX-2 inhibitor, inhibits growth and proliferation of various types of cancer cells by COX-2 dependent and independent mechanisms. In the presented study, the conjugates of biotinylated third generation poly(amidoamine) dendrimer (PAMAM) with covalently linked 18 (G3B18N) and 31 (G3B31N) nimesulide residues were synthesized and characterized by NMR spectroscopy. Biological properties of conjugates were evaluated, including cytotoxicity, proliferation, and caspase 3/7 activities in relation to COX-2/PGE2 axis signaling in human normal fibroblast (BJ) and squamous cell carcinoma (SCC-15). Both conjugates exerted a selective cytotoxicity against SCC-15 as compared with BJ cells at low 1.25–10 µM concentration range and their action in cancer cells was over 250-fold stronger than nimesulide alone. Conjugates overcome apoptosis resistance and sensitized SCC-15 cells to the apoptotic death independently of COX-2/PGE2 axis. In normal human fibroblasts the same concentrations of G3B31N conjugate were less effective in inhibition of proliferation and induction of apoptosis, as measured by caspase 3/7 activity in a manner depending on increase of PGE2 production by either COX-1/COX-2.

Modified Carboxyl-Terminated PAMAM Dendrimers as Great Cytocompatible Nano-Based Drug Delivery System.

Polyamidoamine (PAMAM) dendrimers are extensively researched as potential drug delivery system thanks to their desirable features such as controlled and stable structures, and ease of functionalization onto their surface active groups. However, there have been concerns about the toxicity of full generation dendrimers and risks of premature clearance from circulation, along with other physical drawbacks presented in previous formulations, including large particle sizes and low drug loading efficiency. In our study, carboxyl-terminated PAMAM dendrimer G3.5 was grafted with poly (ethylene glycol) methyl ether (mPEG) to be employed as a nano-based drug delivery system with great cytocompatibility for the delivery of carboplatin (CPT), a widely prescribed anticancer drug with strong side effects so that the drug will be effectively entrapped and not exhibit uncontrolled outflow from the open structure of unmodified PAMAM G3.5. The particles formed were spherical in shape and had the optimal size range (around 36 nm) that accommodates high drug entrapment efficiency. Surface charge was also determined to be almost neutral and the system was cytocompatible. In vitro release patterns over 24 h showed a prolonged CPT release compared to free drug, which correlated to the cytotoxicity assay on malignant cell lines showing the lack of anticancer effect of CPT/mPEG-G3.5 compared with CPT.

Cellular uptake of glucoheptoamidated poly(amidoamine) PAMAM G3 dendrimer with amide-conjugated biotin, a potential carrier of anticancer drugs

In search for soluble derivatives of PAMAM dendrimers as potential carriers for hydrophobic drugs, the conjugates of PAMAM G3 with biotin, further converted into glycodendrimer with d-glucoheptono-1,4-lactone, were prepared. Polyamidoamine dendrimer (PAMAM) of third generation, G3 was functionalized with four biotin equivalents covalently attached to terminal amine nitrogens via amide bond G34B. The remaining 28 amine groups were blocked by glucoheptoamide substituents (gh) to give G34B28gh or with one fluorescein equivalent (attached by reaction of G34B with fluorescein isothiocyanate, FITC) via thiourea bond as FITC followed by exhaustive glucoheptoamidation to get G34B27gh1F. As a control the G3 substituted totally with 32 glucoheptoamide residues, G3gh and its fluorescein labeled analogue G331gh1F were synthesized.The glucoheptoamidation of PAMAM G0 dendrimer with glucoheptono-1,4-lactone was performed in order to fully characterize the 1H NMR spectra of glucoheptoamidated PAMAM dendrimers and to control the derivatization of G3 with glucoheptono-1,4-lactone. Another two derivatives of G3, namely G34B28gh1F′ and G332ghF′, with ester bonded fluorescein were also obtained.Biological properties of obtained dendrimer conjugates were estimated in vitro with human cell lines: normal fibroblast (BJ) and two cancer glioblastoma (U-118 MG) and squamous carcinoma (SCC-15), including cytotoxicity by reduction of XTT and neutral red (NR) assays. Cellular uptake of dendrimer conjugates was evaluated with confocal microscopy.Obtained results confirmed, that biotinylated bioconjugates have always lower cytotoxicity and 3–4 times higher cellular uptake than non-biotinylated dendrimer conjugates in all cell lines. Comparison of various cell lines revealed different dose-dependent cell responses and the lower cytotoxicity of examined dendrimer conjugates for normal fibroblasts and squamous carcinoma, as compared with much higher cytotoxic effects seen in glioblastoma cell line. Synthetized multi-functional conjugate (G34B27gh1F) is a promising candidate as biocompatible vehicle for hydrophobic molecules used in anticancer therapy.

Smart dendrimer-based nanogel for enhancing 5-fluorouracil loading efficiency against MCF7 cancer cell growth

Nano-carriers are not only evaluated as a novel kind of drug delivery, but also expected to bypass the critical bottleneck of conventional cancer chemotherapeutics. Among them, thermo-sensitive nanogel draws much attention due to its efficacy in the loading and release of hydrophobic drugs. In the study, we developed a promising thermosensitive polymer-grafted dendrimer to enhance drug-loading efficiency, which was prepared from conjugation of thermo-sensitive carboxylic-terminated poly(N-isopropylacrylamide) polymer (PNIPAM) with polyamidoamine (PAMAM) dendrimer (G3.0). The obtained copolymer structure and molecular weight were confirmed by proton nuclear magnetic resonance ( 1 H NMR) and gel permeation chromatography (GPC), respectively. Morphology of the nanocarrier was observed around 120–150 nm by transmission electron microscopy (TEM) and 200 nm by dynamic light scattering (DLS). The nanocarrier exhibited the higher drug loading (DL = 7.79%) and entrapment efficiency (EE = 42.25%) of 5-FU compared to PAMAM dendrimer G3.0 (DL = 2.25% and EE = 11.52%). In-vitro test, the 5-FU-loaded in PAMAM G3.0–PNIPAM could release approximately 40% of the encapsulated drug at pH = 7.4 after 5 days tracking, while the cumulative anticancer drugs achieved nearly two-fold increase (around 75%) at pH 5.5 during the same time. Moreover, the cytotoxicity assay results also indicated that the drug-loaded nanocarrier exhibited a significant growth inhibition of the MCF-7 cancer cell. The obtained resulted possibly offered a great potential of the nanocarrier which may be utilized in delivering other anticancer drugs or dual drugs for chemotherapy in future.

Synthesis and Characterization of Photocurable Polyamidoamine Dendrimer Hydrogels as a Versatile Platform for Tissue Engineering and Drug Delivery

In this work, we describe a novel polyamidoamine (PAMAM) dendrimer hydrogel (DH) platform with potential for tissue engineering and drug delivery. With PAMAM dendrimer G3.0 being the underlying carrier, polyethylene glycol (PEG) chains of various lengths (MW = 1500, 6000, or 12000 g mol(-1)) were coupled to the dendrimer to different extents, and the resulting PEGylated PAMAM dendrimers were further coupled with acrylate groups to yield photoreactive dendrimer macromonomers for gel formation. It was found that gelation based on photoreactive PAMAM G3.0 macromonomers was restricted by the degree of PEGylation, PEG chain length, and the distribution of acrylate groups on the dendrimer surface. Further, the architecture of the photoreactive macromonomers affects the structural stability and swelling of the resultant networks. A completely cross-linked network (DH-G3.0-12000(H)) with a high water swelling ratio was created by UV-curing of PAMAM dendrimer G3.0 coupled with 28 PEG 12000 chains in the presence of the eosin Y-based photoinitiating system. The disintegration of DH-G3.0-12000(H) was pH-insensitive. DH-G3.0-12000(H) was found to have similar cytocompatibility to un-cross-linked G3.0-12000(H) but a significantly lower cellular uptake by macrophages. With PAMAM dendrimer G3.5 being the underlying carrier, the dendrimer modified with 43 PEG 1500 chains was able to form a completely cross-linked network (DH-G3.5-1500(H)) by UV-curing in the presence of the eosin Y-based photoinitiating system. DH-G3.5-1500(H) exhibited pH-dependent disintegration. Its disintegration ratio increased with pH. PAMAM dendrimer hydrogels uniquely express the structural characteristics of both PEG hydrogel and PAMAM dendrimer and have potential for various applications in tissue engineering and drug delivery.