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Biosynthetic cell membrane vesicles to enhance TRAIL-mediated apoptosis driven by photo-triggered oxidative stress

Feida Li1,2, Xiaoyan Wang1,2, Ming Wu2,3

  • 1School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, P.R. China.

Biomaterials Science
|May 26, 2022
PubMed

Insights

This study introduces CPT MV, a novel nanoplatform that enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cancer therapy. CPT MV overcomes TRAIL resistance by using light-triggered oxidative stress to boost cancer cell apoptosis.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise for cancer treatment due to tumor specificity and limited side effects.
  • Clinical TRAIL therapy is hindered by short protein half-life and low cancer cell death receptor (DR) expression, leading to therapeutic resistance.

Purpose of the Study:

  • To develop a novel reactive oxygen species (ROS)-dependent nanoplatform, CPT MV, to enhance TRAIL efficacy.
  • To improve TRAIL's *in vivo* circulation stability and amplify TRAIL-induced apoptosis in cancer cells.

Main Methods:

  • CPT MV nanoplatform featuring a Ce6-PLGA core and TRAIL-modified cell membrane shell.
  • Laser irradiation to induce ROS production in targeted cells, upregulating death receptor (DR)5 expression.
  • Investigating the combined intrinsic and extrinsic apoptotic pathways triggered by CPT MV and TRAIL.

Main Results:

  • CPT MV enhanced DR5 expression and triggered cytochrome c (Cyt c) release upon laser irradiation.
  • Upregulated DR5 facilitated the extrinsic apoptosis pathway via caspase 8 and caspase 3 activation.
  • Leaked Cyt c initiated the intrinsic apoptotic pathway, synergistically enhancing TRAIL-induced apoptosis.

Conclusions:

  • CPT MV effectively enhances TRAIL-mediated apoptosis through photo-triggered oxidative stress.
  • The nanoplatform shows significant potential for overcoming tumor resistance to TRAIL therapy in clinical settings.

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