Control of Stimuli Sensitivity in pH-Switchable LCST/UCST-Type Thermosensitive Dendrimers by Changing the Dendrimer Structure

Abstract

Stimuli-sensitive materials, such as pH- and temperature-responsive polymers, are useful as smart materials. Phenylalanine (Phe)-modified polyamidoamine (PAMAM) dendrimers with succinic acid termini, PAMAM-Phe-Suc, have been reported as unique pH-switchable lower critical solution temperature (LCST)-/upper critical solution temperature (UCST)-type thermosensitive polymers. Regulating the phase transition behavior of dendrimers is important for their applications. This study investigated the relationship between the dendrimer structure and stimuli sensitivity. Phe-modified PAMAM dendrimers with cyclohexanedicarboxylate termini (PAMAM-Phe-CHex) and sulfonate termini (PAMAM-Phe-SO3Na) were synthesized. The temperature-dependent transmittance of these aqueous dendrimer solutions was examined at various pH values. PAMAM-Phe-CHex with Phe at all termini (PAMAM-Phe64-CHex) demonstrated a broad UCST-like phase transition at pH 7.0 but lacked an LCST-type phase transition. PAMAM-Phe-CHex with ≤ 27 Phe residues showed both LCST- and UCST-like phase transitions at different pH values, but the phase transition was broad. PAMAM-Phe-SO3Na showed both LCST- and UCST-type phase transitions at different pH values, and the transition temperature increased as the bound Phe number decreased. Thus, the phase transition behavior of PAMAM-Phe-SO3Na dendrimers can be regulated by varying the Phe/PAMAM ratios.

T Cell-Association of Carboxy-Terminal Dendrimers with Different Bound Numbers of Phenylalanine and Their Application to Drug Delivery

“…However, the pH sensitivity tended to decrease with decreasing bound numbers of Phe. Our previous report indicated that the stimuli sensitivity broadened with decreasing bound numbers of Phe in the dendrimer [ 31 ], which is consistent with this result. Thus, our results indicate that the bound number of Phe in the dendrimer is involved not only in the T cell-association property but also in the expression of pH responsiveness.…”

“…In this study, CHex- and Phe-modified dendrimers with different bound numbers of Phe were used to investigate the influence of the dendrimer terminal Phe density on cell association and drug delivery ability. Two types of CHex- and Phe-modified dendrimers, PAMAM-CHex-Phe and PAMAM-Phe-CHex, were synthesized by varying the reaction order of cis -1,2-cyclohexanedicarboxylic anhydride and Phe, as shown in Figure 2 [ 30 , 31 ]. In the synthesis of PAMAM-CHex-Phe, the PAMAM G4 dendrimer was reacted with an excess of cis -1,2-cyclohexanedicarboxylic anhydride, followed by a reaction with Phe-OBzl·Tos and the subsequent deprotection.…”

“…In this study, we used PAMAM-Phe-CHex dendrimers bearing different bound numbers of Phe synthesized in our previous reports [ 29 , 31 ].…”

“… 1 The number of terminal groups of the dendrimer is 64. 2 Refers to our previous reports [ 29 , 31 ]. 3 Calculated as the percentage of the bound number of Phe to dendrimer terminal number (64).…”

Effect of the Formation of Hydrophilic and Hydrophobic–Hydrophilic Associates on the Behavior of Copolymers of N-Vinylpyrrolidone with Methyl Acrylate in Aqueous Solutions

“…Phase transitions in solutions of thermosensitive polymers have been studied for a long time [ 1 , 2 , 3 , 4 ]. This issue is not only of academic [ 3 , 5 , 6 , 7 , 8 , 9 ], but also of direct applied interest.…”