A transformable and self-oxygenated smart probe for enhanced tumor sonodynamic therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Sonodynamic therapy (SDT) shows promise for cancer treatment but faces challenges in sonosensitizer tumor bioavailability and anti-hypoxia capabilities.
• Tumor microenvironment (TME) characteristics, such as hypoxia, limit the efficacy of conventional cancer therapies.

Purpose of the Study:

• To develop a TME-mediated nanomorphology transformation and oxygen self-production strategy to enhance SDT efficacy.
• To synthesize and evaluate a smart probe, Ce6-Leu@Mn2+, for enhanced sonodynamic therapy of liver tumors.

Main Methods:

• Synthesis of a dual-responsive probe (Ce6-Leu@Mn2+) incorporating a GSH and LAP-sensitive unit, CBT group, and Mn2+-chelated Ce6 sonosensitizer.
• Investigation of the probe's self-assembly, TME-triggered nanomorphology transformation (large to small nanoparticles), and subsequent tumor accumulation and penetration in HepG2 liver tumor-bearing mice.
• Assessment of the probe's oxygen production capability via endogenous hydrogen peroxide conversion and its effectiveness in alleviating tumor hypoxia under ultrasound irradiation.

Main Results:

• The Ce6-Leu@Mn2+ probe self-assembled into large nanoparticles in physiological conditions, transforming into smaller particles under dual GSH and LAP stimulation in the TME.
• This transformation led to enhanced tumor accumulation and deeper tissue penetration of the probe.
• The probe effectively converted endogenous hydrogen peroxide to oxygen, mitigating tumor hypoxia and enabling efficient SDT against hypoxic liver tumors in vivo.

Conclusions:

• The developed smart TME-responsive probe, Ce6-Leu@Mn2+, demonstrates significant potential for enhancing sonodynamic therapy.
• The nanomorphology transformation and oxygen self-production strategy effectively address key challenges in SDT, improving tumor bioavailability and anti-hypoxia capabilities.
• This approach offers a noninvasive and efficient strategy for treating malignant and hypoxic tumors.