Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy

Liyun Lin,Wen Pang,Shihui Ding,Xunbin Wei,Bobo Gu,Xinyan Jiang

doi:10.1038/s41377-021-00704-5

Abstract

Photodynamic therapy (PDT), which utilizes light excite photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. However, the advancement of PDT is restricted by the inherent characteristics of PS and tumor microenvironment (TME). It is urgent to explore high-performance PSs with TME regulation capability and subsequently improve the therapeutic outcomes. Herein, we reported a newly engineered PS of polymer encapsulated carbonized hemin nanoparticles (P-CHNPs) via a facile synthesis procedure for boosting photodynamic anticancer therapy. Solvothermal treatment of hemin enabled the synthesized P-CHNPs to enhance oxidative stress in TME, which could be further amplified under light irradiation. Excellent in vitro and in vivo PDT effects were achieved due to the improved ROS (hydroxyl radicals and singlet oxygen) generation efficiency, hypoxia relief, and glutathione depletion. Moreover, the superior in vitro and in vivo biocompatibility and boosted PDT effect make the P-CHNPs a potential therapeutic agent for future translational research.

Highlights

The size and morphology of the synthesized nanoparticles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurement
Facile solvothermal carbonization reaction made hemin lose the iron to form deferrization porphyrin fragments or carbonized products with 1O2 generation capability, and the O, N-containing groups combined with the released Fe ion stemming from hemin deferrization, enabling the formed Carbonized hemin nanoparticles (CHNPs) to act as photosensitizer with oxidative stress amplification capability in tumor microenvironment (TME)
The oxidative stress regulation in TME selectively occurred in tumor site featured with H2O2 overexpression (0.1–1 mM), so OH is only generated in the tumor-specific microenvironment but does little harm to normal tissues

Summary

Introduction

The second leading cause of death currently, is one major public health issue with the increased incidence rate in the past several decades[1]. Various emerging cancer treatment strategies, including gene therapy[2], photodynamic therapy (PDT)[3–5], photothermal therapy (PTT)[6–8], chemodynamic therapy (CDT), etc., have been proposed and demonstrated. Among these newly developed treatment strategies mentioned above, PDT, which utilizes photosensitizer (PS) in the presence of light with a specific wavelength to generate reactive oxygen species (ROS) to irreversibly destroy the targeted diseased tissue, 1993, PDT has been clinically applied to treat various types of cancers[12]. PDT has not yet reached its full potential due to the limitation from PSs and tumor microenvironment (TME). The inherent ROS generation efficiency of emerging PSs was significantly enhanced, the ROS quantity in tumor site and PDT efficiency were still subject to the TME features[19], e.g., limited ROS quantity due to the

Methods

Results

Conclusion