Prodrug nanoassemblies bridged by Mono-/Di-/Tri-sulfide bonds: Exploration is for going further

Lipid-Based Intelligent Vehicle Capabilitized with Physical and Physiological Activation

“…However, this is not universal for drugs that need to occupy the active site for modification, such as paclitaxel-like drugs commonly used in clinical practice. Therefore, Yang et al again chose paclitaxel as a model drug to further investigate the assembly and release of the prodrug in depth and validated the sensitivity of the prodrug for differentiating the response of normal and tumor cells in in vivo and in vitro studies [ 103 ]. Moreover, they also discovered and reported for the first time that trisulfide bonds are also capable of oxidation reactions ( Figure 8(c) ).…”

Critical roles of linker length in determining the chemical and self-assembly stability of SN38 homodimeric nanoprodrugs

“…Moreover, due to the large proportion of the parent drug, the drug loading of HDPNs has been as high as nearly 70% or even higher. 17 These excellent properties contributed to HDPNs' great potentiality towards clinical translation.…”

Probing the Role of Connecting Bonds and Modifying Chains in the Rational Design of Prodrug Nanoassemblies

“…The H 2 O 2sensitive mechanism of the sulfide bonds has been demonstrably clarified in our previous work, since H 2 O 2 could oxidize the sulfur atoms to generate hydrophilic sulfoxide or sulphone, promote the rupture of the ester bond, and then facilitate the release of the free DTX (Figure 3C). 23,30,34 The essence of redox reactions is the gain and loss of electrons, that is, the rise and fall of the chemical valence of atoms. The chemical valence of sulfur in thioether bonds is −2, and the chemical valence of sulfur in disulfide bonds is −1.…”

“…29,33 Among them, the thioether bonds were more sensitive to oxidation, and the disulfide bonds were more sensitive to reduction. 34 However, the effects of thioether and disulfide bonds on drug release and cytotoxicity of prodrug nanoassemblies remain to be further investigated.…”

“…Both the connecting bonds and the modifying chains could affect the self-assembly ability, pharmacokinetics, and pharmacodynamics of the prodrugs. , Connecting bonds worked as linkages between parent drugs and modifying chains, which were crucial for the self-assembly ability and drug release of prodrugs . It has been reported that sulfide bonds, including thioether bonds and disulfide bonds, had a bond angle and dihedral angle closed to 90°, which could generate “structural defects” to enhance the self-assembly capacity of prodrugs. , In addition, it was found that the sulfide bonds could intelligently identify the tumor environment by responding to the elevated intracellular glutathione (GSH) and reactive oxygen species (ROS), thereby triggering the specific release of parent drugs. , Among them, the thioether bonds were more sensitive to oxidation, and the disulfide bonds were more sensitive to reduction . However, the effects of thioether and disulfide bonds on drug release and cytotoxicity of prodrug nanoassemblies remain to be further investigated.…”