Targeted Delivery Prodigiosin to Choriocarcinoma by Peptide-Guided Dendrigraft Poly-<span style="font-variant: small-caps">l</span>-lysines Nanoparticles

• Main Authors: Kai Zhao, Dan Li, Guogang Cheng, Baozhen Zhang, Jinyu Han, Jie Chen, Baobei Wang, Mengxia Li, Tianxia Xiao, Jian Zhang, Dongpo Zhou, Zheng Jin, Xiujun Fan
• Format: Article
• Language: English
• Published: MDPI AG 2019-11-01
• Series: International Journal of Molecular Sciences
• Subjects: dendrigraft poly-<span style="font-variant: small-caps">l</span>-lysines nanoparticles; placenta chondroitin sulfate a binding peptide; <i>serratia marcescens</i> prodigiosin; targeted delivery; choriocarcinoma
• Online Access: https://www.mdpi.com/1422-0067/20/21/5458

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, <i>in vivo</i>, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from <i>Serratia marcescens</i> subsp. <i>lawsoniana</i> was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.