Design of Biocompatible Dendrimers with Environment Sensitivity

Abstract

Dendrimers have attracted much interest because of their unique structures and properties. 1 Their size, structure, and surface properties are highly controllable. Also, their interiors are capable of encapsulating small molecules. 2 Therefore, dendrimers are highly attractive materials for drug delivery applications. 3 Recently, efforts have been made to prepare dendrimers with poly(ethylene glycol) (PEG) chains at the chain ends. 4 Because the dendrimer moieties of PEG-attached dendrimers are covered with highly hydrophilic PEG chains, they may act as nanocapsules with a biocompatible surface. In a previous study, we successfully attached PEG chains to all of the chain ends of thirdand fourth-generation polyamidoamine (PAMAM) dendrimers and showed that these dendrimers have the ability to retain anticancer drugs. 4a In this study, we have attempted to provide the dendrimers with stimuli-sensitive properties because such properties are useful for site-specific or cytoplasmic drug delivery. Here, we report an effective strategy for the sensitization of dendrimers against oxidative or reductive environments using cysteine (Cys).PEG-attached PAMAM dendrimers with Cys residues were synthesized according to Scheme 1. The PAMAM G4 dendrimer, which has N-tert-butoxycarbonyl-S-acetamidomethylcysteine [Boc-Cys(Acm)] residues, was

Comparison of Thermosensitive Properties of Poly(amidoamine) Dendrimers with Peripheral N‐Isopropylamide Groups and Linear Polymers with the Same Groups

“…[4,6] Analysis by 1 H and 13 C NMR spectroscopy demonstrated that essentially every chain terminal of these dendrimers was connected to the corresponding terminal groups of the surface-modified dendrimers (see the Supporting Information). Figure 1 depicts the temperature dependence of the light transmittance of solutions of various NIPAM-terminated dendrimers and linear polymers with NIPAM groups in a phosphate solution (10 mm, pH 9.0) at 500 nm.…”

Dendrimer-based bionanomaterials produced by surface modification, assembly and hybrid formation

“…Based on this idea, we attached L-cysteine residues onto the dendrimer surface moiety of PEG-modified PAMAM G4 dendrimer (Figure 2d). 21 A thiol group of a cysteine side group can form a disulfide linkage with the thiol group of an adjacent cysteine residue in an oxidative environment, resulting in the formation of a dense shell. However, in a reductive environment, the disulfide linkage is cleaved to generate thiol groups.…”

Synthesis of Structurally‐Controlled AIDS Vaccine Model with Glyco‐Peptide Dendrimer Scaffolds

“…[37,39] A dialyzing tube (MWCO 2000; Spectrum Laboratories, Inc.) was used for the purification of sugarcontaining poly(lysine) dendrimers and vaccine models. 1 H NMR spectra were recorded on a JEOL Alpha-500 NMR spectrometer. Chemical shifts (d ¼ 0 ppm) were referred to TMS with the residual proton of the solvents.…”

“…[1][2][3][4] Since the dendrimer has a well-defined structure, regular branching pattern, and multiple peripheral groups for drug or antigen attachment, it possesses beneficial characteristics for drug or antigen delivery. [5][6][7] We have investigated the synthesis and anti-HIV (human immunodeficiency virus) activity of sulfated polysaccharides as an acquired immunodeficiency syndrome (AIDS) drug.…”