Investigation and intervention of autophagy to guide cancer treatment with nanogels

Area of Science:

• Biomedical Engineering
• Cell Biology
• Cancer Research

Background:

• Cancer cells exploit autophagy for survival against harsh conditions and chemotherapy.
• Nanogels are promising drug carriers for cancer treatment, but their impact on autophagy is unclear.

Purpose of the Study:

• To investigate the intracellular trafficking of nanogels.
• To determine the effect of nanogels on autophagy.
• To explore the potential of combining nanogels with autophagy inhibitors for enhanced cancer therapy.

Main Methods:

• Utilized Rab proteins and LC3 as markers for endocytosis and autophagy, respectively.
• Tracked Rhodamine B-labeled nanogels' intracellular journey using microscopy.
• Assessed the impact of nanogels on autophagy in cancer cells.
• Evaluated the efficacy of co-delivering nanogels with autophagy inhibitors (chloroquine) and doxorubicin in a mouse tumor model.

Main Results:

• Nanogels were internalized via protein-dependent endocytosis and micropinocytosis.
• Nanogels trafficked through various Rab-positive vesicles (early endosomes, late endosomes, recycling endosomes, lipid droplets) to lysosomes.
• Nanogels were found to induce autophagy and become sequestered in autophagosomes.
• Co-delivery of nanogels with chloroquine and doxorubicin significantly reduced tumor volume and weight in mice.

Conclusions:

• Nanogels interact with the autophagy pathway, potentially being sequestered in autophagosomes.
• Autophagosomes may receive nanogels from multiple Rab-positive vesicles.
• Co-delivery of nanogels with autophagy inhibitors offers a promising strategy to enhance anticancer nanogel therapy by modulating the autophagy pathway.