Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Abstract

Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxel-fatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cis-trans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

“…The 3-dimensional structures of BNN6 and DiR with optimal combination formulation (3:1) were obtained using the Autodock Vina software. The runtime parameters and environment were consistent with the literature 47 . Moreover, the intermolecular interaction breakers (SDS, NaCl, and urea, 50 nM) were co-incubated with the B-BD NAs and T-BD NAs to determine the intermolecular forces.…”

“…To screen the optimal synergistic dose radio of BNN6 and DiR, we first constructed the bared BNN6 and DiR co-assembly (B-BD NAs) using a nano-precipitation method 47 . In brief, 10 mg of BNN6 and 10 mg of DiR were dissolved in methanol (1 mL), respectively.…”

Immunogenic Nanovesicle‐Tandem‐Augmented Chemoimmunotherapy via Efficient Cancer‐Homing Delivery and Optimized Ordinal‐Interval Regime

“…This provides a good foundation for developing a drug delivery systemDDS for cancer therapy. [ 34 , 35 , 36 ] Therefore, we first prepared a disulfide bond‐bridged PD1 nano‐cluster (S‐PD), in which the TEM showed a distinct spherical structure with a particle size of ≈150 nm (Figure S14 , Supporting Information). Then, the PD1 solution was co‐incubated with TDEVs with disulfide bond‐containing linkers in a homothermal shaker at 37 °C for 1 h to produce S‐PDNGs with cancer homing and reduction sensitivity.…”

Reduction-Responsive Stearyl Alcohol-Cabazitaxel Prodrug Nanoassemblies for Cancer Chemotherapy

“…For instance, we previously lucubrated the impact of disulfide bond bridge on paclitaxel (PTX)-oleic acid prodrug nanoassemblies and found that disulfide linkages could achieve effective reductive-selective drug release in response to excessive intracellular reductive glutathione (GSH) at tumor sites, greatly alleviating the side effects and improving antineoplastic efficacies [ 26 ]. Except for selective responsiveness, disulfide bonds also contribute to the self-assembly of prodrug-based nano-DDS by introducing molecular “structure defects” [ 27 , 28 ]. What is more, the distance between the disulfide bond and the ester bond is a pivotal point that has a great influence on drug release, cytotoxicity and antitumor efficacy in vivo [ 29 , 30 ].…”