Integrated H2O2 self-supplying PLGA@CQDs–CuPox nanoparticles enabling accumulation of copper during the Fenton reaction

Abstract

Chemodynamic therapy is an emerging therapeutic modality that utilizes the Fenton reaction for the production of reactive oxygen species to selectively target and kill cancer cells. In recent years, there has been a notable increase in the demand for developing nanomedicines with enhanced Fenton catalytic efficiency, self-generating H₂O₂ capability, and superior biocompatibility. This study focuses on the synthesis of a new nanomedicine, PLGA@carbon quantum dots-copper peroxide nanoparticles (PLGA@CQDs–CuPox NPs). The CQD nanodots exhibited the highest fluorescence intensity at an excitation wavelength of 400 nm. CuPox nanodots exhibited superior Fenton catalytic performance at a pH value of 5.5. In vitro experiments demonstrated that PLGA@CQDs–CuPox NPs achieved a killing rate of over 85% for tumor cells while showing a lower killing rate of 10% for normal cells. Upon entering tumor cells, PLGA@CQDs–CuPox NPs underwent degradation, releasing CQDs and CuPox nanodots. CQD nanodots emitted fluorescence, whereas CuPox nanodots decomposed to initiate a Fenton-like reaction. Through the enhanced permeability and retention effect, these nanoparticles penetrated deeper into the tumor cells, enabling deep-seated chemodynamic therapy. Uptake experiments further demonstrated that PLGA@CQDs–CuPox NPs escaped from lysosomes and entered the cell nucleus, utilizing the fluorescence changes of CQD nanodots to determine the optimal treatment time. The design of PLGA@CQDs–CuPox NPs offers a novel approach for precise cancer diagnosis and effective treatment through fluorescence imaging-guided chemodynamic therapy based on tumor microenvironment responsiveness.