Background: Doxorubicin (DOX) is one of the most effective treatments for hepatocellular carcinoma (HCC), but is restricted by its poor pharmacokinetics. Herein, we exploited efficient targeted drug delivery systems and they have been found to be a worthy strategy for liver cancer therapy. Materials and methods: We investigated polymeric nanoparticles which were synthesized based on host-guest interaction between β-cyclodextrin and benzimidazole. The properties of nanoparticles with regard to size/shape, encapsulation efficiency, and drug release were investigated using conventional experiments. Cell proliferation assay in vitro, cell uptake assay, and cell apoptosis analysis were used to investigate cytotoxicity, uptake, and mechanism of targeted supramolecular prodrug complexes (TSPCs)-based self-assemblies and supramolecular prodrug complexes (SPCs)-based self-assemblies. Results: The pH-sensitive lactobionic acid (LA)-modified pH-sensitive self-assemblies were synthesized successfully. The results of in vitro released assay showed that the accelerated released of DOX from TSPCs-based self-assemblies with the decrease of pH value. When TSPCs-based self-assemblies were taken up by HepG2 cells, they demonstrated a faster release rate under acidic conditions and proved to have higher cytotoxicity than in the presence of LA. A mechanistic study revealed that TSPCs-based self-assemblies inhibited liver cell proliferation by inducing cell apoptosis. Conclusion: The pH-sensitive nanocomplex, as liver-targeted nanoparticles, facilitated the efficacy of DOX in HepG2 cells, offering an appealing strategy for the treatment of HCC.
Supramolecular polymer vesicles (SPVs) with stimuli‐responsive features are promising multifunctional nanocarriers; however, improving the stability and developing multiple‐drug‐loaded SPVs remain key issues in this field. In this work, cross‐linked supramolecular hyperbranched polymer vesicles (SHPVs) with redox‐responsiveness are first constructed based on an AB2‐type macromonomer‐synthesized SHP. The obtained cross‐linked SHPVs exhibit much better size stability than those of non‐cross‐linked branched self‐assemblies, and higher double‐drug‐loading capacity compared with linear supramolecular polymer self‐assemblies. Particularly, these cross‐linked SHPVs exhibit a redox‐triggered, controlled double‐drug release behavior upon the addition of H2O2.
The realization of multistage-controlled drug delivery at the cell level through the morphology transitions of supramolecular self-assemblies (SSA) is still a challenge. Herein, successive morphology transitions of SSA with pH responsiveness were successfully achieved through the subsequent action of ultrasound and redox stimuli. Specifically, we first prepared noncovalently PEGylated spherical self-assemblies formed by host−guestconjugated amphiphilic β-CD dimers. The functionalized PEG could be associated/disassociated onto the spherical self-assemblies by adjusting pH values of solutions. They could reassemble into branched self-assemblies induced by ultrasonication. Such branched self-assemblies could be further dissociated into second spherical self-assemblies under a redox stimulus. This morphology transition process was used to conduct triple-controlled targeted drug delivery and release in cancer cells. This work will be beneficial for the design of smart SSA for controlled release in vivo.
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