Tongwen Xu

Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives

In the past decade, nanomedicine with its promise of improved therapy and diagnostics has revolutionized conventional health care and medical technology. Dendrimers and dendrimer-based therapeutics are outstanding candidates in this exciting field as more and more biological systems have benefited from these starburst molecules. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumour via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Imaging agents including MRI contrast agents, radionuclide probes, computed tomography contrast agents, and fluorescent dyes are combined with the multifunctional nanomedicine for targeted therapy with simultaneous cancer diagnosis. However, an important question reported with dendrimer-based therapeutics as well as other nanomedicines to date is the long-term viability and biocompatibility of the nanotherapeutics. This critical review focuses on the design of biocompatible dendrimers for cancer diagnosis and therapy. The biocompatibility aspects of dendrimers such as nanotoxicity, long-term circulation, and degradation are discussed. The construction of novel dendrimers with biocompatible components, and the surface modification of commercially available dendrimers by PEGylation, acetylation, glycosylation, and amino acid functionalization have been proposed as available strategies to solve the safety problem of dendrimer-based nanotherapeutics. Also, exciting opportunities and challenges on the development of dendrimer-based nanoplatforms for targeted cancer diagnosis and therapy are reviewed (404 references).

Targeting cancer cells with biotin–dendrimer conjugates

Star-burst dendrimers represent a superior carrier platform for targeted drug delivery. Partially acetylated generation 5 (G5) polyamidoamine (PAMAM) dendrimer was conjugated with the targeting moiety (biotin) and the imaging moiety (fluoresceinisothiocyanate, FITC), and the resulting dendrimer-biotin conjugate was characterized by (1)H NMR, UV-vis spectrum. As revealed by flow cytometry and confocal microscopy, the bifunctional conjugate (dendrimer-biotin-FITC) exhibited much higher cellular uptake into HeLa cells than the conjugate without biotin. The uptake was energy-dependent, dose-dependent, and could be effectively blocked by dendrimer-conjugated biotin. Our results indicated that the biocompatible biotin-dendrimer conjugate might be a promising nano-platform for cancer therapy and cancer diagnosis.

Pharmaceutical applications of dendrimers: promising nanocarriers for drug delivery.

Dendrimers are new artificial macromolecules which have the structure like a tree. They are hyperbranched and monodisperse three-dimensional molecules with defined molecular weights, large numbers of functional groups on the surface and well-established host-guest entrapment properties. Recently, dendrimers have successfully proved themselves as promising nanocarriers for drug delivery because they can render drug molecules a greater water-solubility, bioavailability, and biocompatibility. In this review, recent progress in the pharmaceutical applications of dendrimers as delivery systems for drugs, particularly, the non-steroidal anti-inflammatory, anti-microbial/anti-viral and potent anti-cancer drugs is discussed. Three possible interaction mechanisms between dendrimers and drug molecules are presented. In addition, the pharmacodynamic and pharmacokinetic properties of both dendrimer/drug complex and dendrimer-drug conjugation after their administration to animals are evaluated.

The effect of dendrimers on the pharmacodynamic and pharmacokinetic behaviors of non-covalently or covalently attached drugs.

Dendrimers are a new class of artificial macromolecules with several attractive properties that show promises in several biomedical applications. They can be widely used to increase the cellular uptake, bioavailability and therapeutic efficacy, to optimize the biodistribution and intracellular release profile, and to reduce the systemic toxicity, clearance and degradation rate of non-covalently or covalently attached drugs. Recent studies in this aspect clearly point to the potential advantages of dendrimers for the design of new drug delivery systems. Before final applications of dendrimer-based drug delivery systems in humans, we should not only address the benefits of these systems, but also assess the long-term pharmacodynamic (PD) and pharmacokinetic (PK) behaviors and health risk of them. In this mini-review, we will mainly discuss the influence of dendrimers on the PD and PK behaviors of drugs complexed or conjugated to them.

NMR Insights into Dendrimer-Based Host–Guest Systems

Jingjing Hu,‡ Tongwen Xu,‡ and Yiyun Cheng*,†,§ †Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, People’s Republic of China ‡CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, People’s Republic of China Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai, 200062, P.R.China

Alkaline polymer electrolytes containing pendant dimethylimidazolium groups for alkaline membrane fuel cells

Novel anion exchange membranes (AEMs), based on poly(phenylene oxide) (PPO) chains linked to pendant 1,2-dimethylimidazolium (DIm) functional groups, have been prepared for evaluation in alkaline polymer electrolyte membrane fuel cells (APEFCs). Successful functionalisation of the PPO chains was confirmed using 1H-NMR and FT-IR spectroscopies. The ionic conductivities of the resulting DIm–PPO AEMs at 30 °C are in the ranges of 10–40 mS cm−1 and 18–75 mS cm−1 at 60 °C. The high ionic conductivities are attributed to the highly developed microstructures of the membranes, which feature well-defined and interconnected ionic channels (confirmed by atomic force microscopy, AFM, measurements). Promisingly, the ion-exchange capacities (IECs) of the DIm–PPO AEM are maintained after immersion in an aqueous KOH solution (2 mol dm−3) for 219 h at 25 °C; a previously developed monomethyl imidazolium PPO analogue AEM (Im–PPO) showed a significant decline in IEC on similar treatment. This reduction in undesirable attack by the OH− conducting anions is ascribed to an increase in steric interference and removal of the acidic C2 proton [in the monomethyl Im-groups] by the methyl group in the DIm cationic ring. Moreover, the maximum power densities produced in simple beginning-of-life single cell H2/O2 fuel cell tests increased from 30 mW cm−2 to 56 mW cm−2 when switching from the Im–PPO AEM (fuel cell temperature = 50 °C) to the DIm–PPO-0.54 AEM (fuel cell temperature = 35 °C) respectively (even with the use of lower temperatures).

External Electrostatic Interaction versus Internal Encapsulation between Cationic Dendrimers and Negatively Charged Drugs: Which Contributes More to Solubility Enhancement of the Drugs?

Relationships of electrostatic interaction and encapsulation between poly(amidoamine) (PAMAM) dendrimers and negatively charged drug molecules have been investigated by aqueous solubility and NMR ( (1)H NMR and two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY)) studies. PAMAM dendrimers significantly increased the solubilities of phenobarbital and sulfamethoxazole, but scarcely influenced those of primidone and trimethoprim. Moreover, (1)H NMR and 2D-NOESY measurements indicated that few phenobarbital or sulfamethoxazole molecules were entrapped in the cavities of low-generation dendrimers (generation 3, G3). These results suggest that external electrostatic interaction contributes more to the solubility enhancement of drugs than internal encapsulation.

Preparation of zwitterionic hybrid polymer and its application for the removal of heavy metal ions from water

A series of zwitterionic hybrid polymers were prepared from the ring-opening polymerization of pyromellitic acid dianhydride (PMDA) and phenylaminomethyl trimethoxysilane (PAMTMS), and a subsequent sol-gel process. FTIR spectra confirmed the step products. TGA analysis showed that the thermal degradation temperature increased with an increase in PMDA content. As a typical example, sample B was used to separate Cu(2+) and Pb(2+) removal by adsorption. It was indicated that its adsorption for Cu(2+) and Pb(2+) followed Lagergren second-order kinetic model and Langmuir isotherm model, demonstrating that the adsorption process might be Langmuir monolayer adsorption. Meanwhile, it was found that the adsorption capacity of Pb(2+) on sample B is beyond 12 times higher than that of Cu(2+) in 0.1 mol dm(-3) aqueous solution, revealing that it has larger affinity for Pb(2+). The desorption efficiency of Cu(2+) and Pb(2+) in 1 mol dm(-3) HNO(3) solution reached up to 96 and 89%, respectively; indicating that they can be regenerated and recycled in industry. These findings suggest that they are promising adsorbents for the selective removal of Pb(2+) from Pb(2+)/Cu(2+) mixed aqueous solution, and can be applied to separate and recover the heavy metal ions from contaminated water and waste chemicals.

Potential of poly(amidoamine) dendrimers as drug carriers of camptothecin based on encapsulation studies

Camptothecin (CPT), a plant alkaloid isolated from Camptotheca acuminata, has an extremely low solubility in aqueous medium, which presents a major challenge during drug formulation in clinical trails. In the present study we investigated the potential of poly(amidoamine) (PAMAM) dendrimers as drug carriers of CPT through aqueous solubility studies. Results showed that the aqueous solubility of CPT was significantly increased by PAMAM dendrimers. The effect of PAMAM generation on CPT solubility was also evaluated. These studies indicated that PAMAM dendrimers might be considered as biocompatible carriers of CPT.

Host−Guest Chemistry and Physicochemical Properties of the Dendrimer−Mycophenolic Acid Complex

The nature of the dendrimer-mycophenolic acid (MPA) complex was investigated by (1)H NMR and 2D NOESY spectroscopy. The (1)H NMR analysis proved that the water-soluble supramolecular structure of the complex was formed based on ionic interactions between dendrimers and MPA molecules on the surface as well as hydrophobic interactions/hydrogen-bond interactions in the interior pockets of dendrimers. The 2D NOESY analysis predicted the localization of MPA molecules in the pockets of dendrimers and gave information on the detailed interactions between dendrimer scaffolds and MPA molecules in the interior. Further solubility and release studies investigated the physicochemical properties of the dendrimer-MPA complexes. These results showed that the host-guest chemistry of dendrimer-MPA complexes proposed by NMR techniques explains the solubilization and release behavior of MPA in the presence of PAMAM dendrimers well. The general host-guest chemistry of the dendrimer-drug complex is promising for the development of new drug delivery systems.