GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Developing effective nanomedicine requires precise tumor targeting, deep penetration, and sustained retention.
• Stimuli-responsive drug delivery systems offer potential for improved therapeutic outcomes.

Purpose of the Study:

• To develop a stepwise stimuli-responsive nanomedicine strategy for enhanced cancer therapy.
• To improve tumor targeting, penetration, and retention using iRGD peptide and shape-transformable nanoparticles.

Main Methods:

• Co-administration of iRGD peptide with shape-transformable, glutathione-responsive SN38-dimer loaded nanoparticles (d-SN38@NPs).
• Utilized 650 nm laser irradiation for nanoparticle-to-nanofiber transformation and reactive oxygen species generation.
• Assessed *in vitro* cellular uptake, apoptosis, and spheroid penetration.
• Evaluated *in vivo* tumor accumulation, penetration, suppression, and toxicity in a 4T1 tumor-bearing mouse model.

Main Results:

• d-SN38@NPs/iRGD demonstrated high drug loading efficiency (33.92%) and effective tumor penetration.
• Laser irradiation induced nanoparticle-to-nanofiber transformation, enhancing retention and releasing reactive oxygen species.
• Glutathione-responsive release of SN38 resulted in a combined chemo-photodynamic effect.
• *In vitro* studies showed increased cellular uptake, apoptosis, and spheroid penetration.
• *In vivo* studies achieved 60.89% tumor suppression with a favorable toxicity profile.

Conclusions:

• The combined strategy of iRGD peptide and structural transformable nanoparticles significantly enhances tumor targeting, penetration, and retention.
• This novel approach empowers anticancer efficacy through synergistic chemo-photodynamic therapy.
• The developed nanomedicine holds promise for improved cancer treatment with reduced systemic toxicity.