Biomimetic Cascade Polymer Nanoreactors for Starvation and Photodynamic Cancer Therapy.

Shengda Liu,Jiayun Xu,Junqiu Liu,Jianxin Sun,Fei Li,Shuangjiang Yu,Tengfei Yan,Hongcheng Sun

doi:10.3390/molecules26185609

Shengda Liu, Jiayun Xu + Show 6 more

Open Access

https://doi.org/10.3390/molecules26185609

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Abstract

The selective disruption of nutritional supplements and the metabolic routes of cancer cells offer a promising opportunity for more efficient cancer therapeutics. Herein, a biomimetic cascade polymer nanoreactor (GOx/CAT-NC) was fabricated by encapsulating glucose oxidase (GOx) and catalase (CAT) in a porphyrin polymer nanocapsule for combined starvation and photodynamic anticancer therapy. Internalized by cancer cells, the GOx/CAT-NCs facilitate microenvironmental oxidation by catalyzing endogenous H2O2 to form O2, thereby accelerating intracellular glucose catabolism and enhancing cytotoxic singlet oxygen (1O2) production with infrared irradiation. The GOx/CAT-NCs have demonstrated synergistic advantages in long-term starvation therapy and powerful photodynamic therapy (PDT) in cancer treatment, which inhibits tumor cells at more than twice the rate of starvation therapy alone. The biomimetic polymer nanoreactor will further contribute to the advancement of complementary modes of spatiotemporal control of cancer therapy.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
To extend the therapeutic effect, a complementary mode that cuts off the glucose supply to the cancer and destroys the cellular components associated with glucose metabolism was proposed
Polymer nanocapsules were prepared by the polymerization of porphyrin-based building blocks containing tyrosine upon horseradish peroxidase (HRP) and H2 O2 addition

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Once glucose supply is interrupted, tumor growth is preferentially inhibited; glucose metabolism-related cancer starvation therapy is increasingly regarded as a promising clinical translational approach [10,11,12,13]. Polymer nanocapsules with porphyrin PSs as building blocks were constructed based on HRP-catalyzed tyrosine dimerization. The cascade reaction of GOx/CAT-NCs promoted O2 production catalyzed by endogenous H2 O2 , speeding up glucose catabolism and accelerating cytotoxic 1 O2 production under infrared irradiation, according to the following equations: CAT. The generated O2 enhanced the glucose catabolism by GOx, strengthening the effect of starvation therapy, and promoted the production of cytotoxic 1 O2 , improving the effect of PDT.

Characterization of Polymer Nanocapsules

Synthesis

Cell Culture and Cytotoxicity Assays

Conclusions