Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 36, Pages 42411-42428Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c10325
Keywords
exosomes; TRAIL; targeting drug delivery; triptolide; malignant melanoma
Funding
- National Natural Science Foundation of China (China) [81873011, 82074272]
- Science and Technology Commission of Shanghai Municipality (China) [21XD1403400]
- Outstanding Talents Programof Shanghai Health and Family Planning Commission (China) [2018BR27]
- Shanghai Sailing Program (China) [20YF1412100]
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The study proposes a delivery system based on TRAIL-engineered exosomes (TRAIL-Exo) for loading TPL for targeted therapy against malignant melanoma, which improves tumor targetability, enhances cellular uptake, inhibits proliferation, invasion, and migration, and induces apoptosis of A375 cells through activating the extrinsic TRAIL pathway and the intrinsic mitochondrial pathway in vitro. Intravenous injection of TRAIL-Exo/TPL significantly suppresses tumor progression and reduces the toxicity of TPL in the melanoma nude mouse model, presenting a novel strategy for high-efficiency exosome-based drug-delivery nanocarriers with synergistic therapeutic efficacy and targeting capacity for melanoma treatment.
Malignant melanoma is considered the most aggressive skin carcinoma with invasive growth patterns. Triptolide (TPL) possesses various biological and pharmacological activities involved in cancer treatment. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce cancer cell apoptosis by binding to DR5 highly expressed on cancer cells. Exosomes are natural nanomaterials with low immunogenicity, nontoxicity, and excellent biocompatibility and have been extensively used as emerging delivery vectors for diverse therapeutic cargos. Herein, a delivery system based on TRAIL-engineered exosomes (TRAIL-Exo) for loading TPL for targeted therapy against malignant melanoma is proposed and systematically investigated. Our results showed that TRAIL-Exo/TPL could improve tumor targetability, enhance cellular uptake, inhibit proliferation, invasion, and migration, and induce apoptosis of A375 cells through activating the extrinsic TRAIL pathway and the intrinsic mitochondrial pathway in vitro. Moreover, intravenous injection of TRAIL-Exo/TPL significantly suppressed tumor progression and reduced the toxicity of TPL in the melanoma nude mouse model. Together, our research presents a novel strategy for high-efficiency exosome-based drug-delivery nanocarriers and provides an alternative dimension for developing a promising approach with synergistic therapeutic efficacy and targeting capacity for melanoma treatment.
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