Highly-controllable drug release from core cross-linked singlet oxygen-responsive nanoparticles for cancer therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery Systems

Background:

• Nanoparticle-based tumor therapy aims for controlled drug release, minimizing leakage in healthy tissues and maximizing delivery to tumors.
• Developing stimuli-responsive drug-conjugation strategies, particularly those utilizing reactive oxygen species (ROS) generated by photodynamic therapy (PDT), is crucial for targeted drug delivery.
• ROS can induce cytotoxicity and trigger the cleavage of specific linkers, enabling controlled nanoparticle degradation and drug release.

Purpose of the Study:

• To design and synthesize novel ROS-responsive nanoparticles for highly-controllable drug release in tumor therapy.
• To create nanoparticles capable of self-stimulating drug release through the simultaneous encapsulation of a photosensitizer and a chemotherapeutic drug.
• To investigate the efficacy of these nanoparticles in achieving targeted drug delivery and enhanced antitumor effects.

Main Methods:

• Thioketal (TK) linkers, reactive to singlet oxygen (SO), were conjugated to polyphosphoesters (PPE) via click chemistry to form core cross-linked SO-responsive PPE nanoparticles (TK-PPE).
• TK-PPE nanoparticles were co-loaded with the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic drug doxorubicin (DOX), creating TK-PPE_Ce6&DOX.
• The stability of TK-PPE_Ce6&DOX in normal physiological conditions and its drug release profile upon 660 nm laser irradiation (inducing SO generation) were evaluated.

Main Results:

• The synthesized TK-PPE_Ce6&DOX nanoparticles demonstrated high stability in normal physiological environments, preventing premature drug leakage.
• Upon 660 nm laser irradiation, encapsulated Ce6 generated SO, leading to the cleavage of TK-linkers and subsequent triggered release of DOX.
• The self-stimulated, highly-controllable drug release mechanism significantly enhanced antitumor efficacy compared to conventional methods.

Conclusions:

• The developed TK-PPE_Ce6&DOX nanoparticles offer a promising platform for on-demand chemotherapy with improved control over drug release.
• Simultaneous encapsulation of a photosensitizer and drug within ROS-responsive nanoparticles enables self-stimulation of drug release, enhancing therapeutic outcomes.
• This approach represents a significant advancement in nanoparticle-based tumor therapy, potentially leading to more effective and safer cancer treatments.