Mitochondria-targeted nanospheres with deep tumor penetration for photo/starvation therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Solid tumor physiology impedes anticancer drug delivery, posing challenges for effective cancer treatment.
• Developing advanced therapeutic strategies for 3D tumors is crucial.

Purpose of the Study:

• To design novel poly lactic-co-glycolic acid (PLGA) nanospheres for synergistic cancer therapy.
• To achieve deep tumor penetration and selective mitochondrial accumulation.
• To enable dual-imaging guided phototherapy and enzyme-induced starvation therapy.

Main Methods:

• Development of IR780 and glucose oxidase (GOx) loaded PLGA nanospheres.
• In vitro 3D tumor modeling and in vivo tumor reconstruction to assess penetration.
• Evaluation of mitochondria-targeting capability and synergistic therapeutic effects.
• Utilizing photoacoustic (PA) and fluorescence (FL) dual imaging for guidance and monitoring.

Main Results:

• Nanospheres demonstrated deep penetration into 3D tumors and selective mitochondrial accumulation.
• Synergistic treatment combining phototherapy and GOx-induced starvation therapy showed enhanced tumor cell damage.
• Mitochondria-targeted phototherapy proved efficient due to mitochondrial susceptibility.
• GOx-induced starvation therapy exacerbated energy metabolism disorders post-phototherapy.

Conclusions:

• The designed nanospheres offer a promising platform for cancer theranostics.
• Dual-modality therapy (phototherapy and starvation) combined with dual-imaging guidance enhances therapeutic outcomes.
• The nanospheres effectively address the challenges of drug delivery in 3D tumors.