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. 2022 Jan 11;20(1):33.
doi: 10.1186/s12951-021-01237-0.

GOx-assisted synthesis of pillar[5]arene based supramolecular polymeric nanoparticles for targeted/synergistic chemo-chemodynamic cancer therapy

Jin Wang #  1 , Di Wang #  1 , Moupan Cen  1 , Danni Jing  1 , Jiali Bei  1 , Youyou Huang  1 , Jiannan Zhang  1 , Bing Lu  1 , Yang Wang  2 , Yong Yao  3
Affiliations

GOx-assisted synthesis of pillar[5]arene based supramolecular polymeric nanoparticles for targeted/synergistic chemo-chemodynamic cancer therapy

Jin Wang et al. J Nanobiotechnology. .

Abstract

Background: Cancer is the most serious world's health problems on the global level and various strategies have been developed for cancer therapy. Pillar[5]arene-based supramolecular therapeutic nano-platform (SP/GOx NPs) was constructed successfully via orthogonal dynamic covalent bonds and intermolecular H-bonds with the assistance of glucose oxidase (GOx) and exhibited efficient targeted/synergistic chemo-chemodynamic cancer therapy.

Methods: The morphology of SP/GOx NPs was characterized by DLS, TEM, SEM and EDS mapping. The cancer therapy efficinecy was investigated both in vivo and in vitro.

Results: SP/GOx NPs can load drug molecules (Dox) and modify target molecule (FA-Py) on its surface conveniently. When the resultant FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently, where GOx can catalyst the overexpressed glucose to generate H2O2. Subsequently, the generated H2O2 in cancer cells catalyzed by ferrocene unit to form •OH, which can kill cancer cells. Furthermore, the loaded Dox molecules released under acid microenvironment, which can further achieve chemo-therapy.

Conclusion: All the experiments showed that the excellent antitumor performance of FA-Py/SP/GOx/Dox NPs, which provided an new method for pillar[5]arene-based supramolecular polymer for biomedical applications.

Keywords: Host-guest interactions; Pillar[5]arene; Supramolecular polymers; Synergistic therapy.

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Conflict of interest statement

The author declare that they have no competing interests.

Figures

Scheme 1.
Scheme 1.
a Chemical structures of amino group modified pillar[5]arene (AP5), ferrocene dicarbaldehyde (FeE), and target molecule FA-Py. b The illustration of preparation and modification of pillar[5]arene-based supramolecular therapeutic nano-platform. c The targeted synergistic chemo-chemodynamic cancer therapy of the multifunctional FA-Py/SP/GOx/Dox NPs
Fig. 1
Fig. 1
a DLS study of SP/GOx NPs dispersed in water. b TEM image and c Enlarged SEM image of SP/GOx NPs. d–h EDS mapping images of SP/GOx NPs
Fig. 2
Fig. 2
a Time-dependent UV–visible spectra of the solution containing SP/GOx NPs, H2O2, and TMB ([TMB] = 0.25 mmol, [H2O2] = 1.00 mmol, SP/GOx NPs: 0.15 mg). b Electron spin resonance spectra of •OH trapped by DMPO in SP/GOx NPs + PBS + GO (blue line), SP/GOx NPs + PBS (red line) and PBS (black line). c CLSM image of •OH generation in HeLa cells after different treatments with DCFH-DA as the probe
Fig. 3
Fig. 3
a Dox release profiles from SP/GOx NPs at pH 3.5, pH 4.8, pH 6.0 and pH 7.4, respectively. b Cell viabilities of HeLa cells incubated with SP NPs, SP/GOx NPs, FA-Py/SP/GOx NPs, SP/Dox NPs, FA-Py/SP/Dox NPs, and FA-Py/SP/GOx/Dox NPs at different concentrations. c Fluorescence images of Calcein AM (live cells, green) and PI (dead cells, red) costained HeLa cells after different groups
Fig. 4
Fig. 4
a Body weight curves and b normalized tumor volume curves of tumor-bearing KM mice in different treatment groups. c Representative tumor photograph at 21th day. d H&E and e TUNEL staining of tumors in corresponding groups
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