Engineering adipocytes for targeting delivery of triptolide derivative and Ce6 for malignant melanoma cytotoxic-PDT synergistic strategy
Yunan Zhao, Yongwei Gu, Qi Fu, Aixue Li, Xiaomeng Tang, Dan Li, Xin Wu, Jiyong Liu
Abstract
Malignant melanoma (MM) is an aggressive and easily metastatic cancer that is poorly responsive to current therapy. The crosstalk between melanoma cells and tumor-associated adipocytes (TAA) plays an important role in the progression of MM, which could be leveraged for anticancer treatment. Here, mature adipocytes (Apo) were engineered for encapsulating a palmitic acid-conjugated triptolide derivative (pTP) and photosensitizer Ce6 (named as pTP-Ce6-Apo), to induce a cytotoxic and photodynamic treatment in malignant melanoma. After para-tumor administration, lipolysis releases pTP and Ce6 that is triggered by intracellular glutathione (GSH) and laser irradiation, respectively, subsequently inducing a variety of pathways, inducing the caspase apoptosis program; generation of reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress. Overall, pTP-Ce6-Apo exhibited excellent antitumor performance and high safety, which is desired for MM therapy.