Abstract
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, in vivo, 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 Serratia marcescens subsp. lawsoniana 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.
Highlights
Cancer has been a major threat to human health in recent years [1,2,3]
To investigate whether the dendrigraft poly-L-lysines (DGL)/chondroitin sulfate (CSA)-PNPs promote cancer-cell apoptosis via the mitochondria-cytochrome c pathway, including caspase-3, caspase-9, bcl-2 and bax, the protein expression of key regulators was analyzed in JEG3 cells and the tumors treated with DGL/CSA-PNPs
The active caspase-3 and caspase-9 bax were significantly induced in the DGL/CSA-PNPs-treated group compared to the control JEG3 cells or tumors (Figures 6A,B and 7)
Summary
Cancer has been a major threat to human health in recent years [1,2,3]. In the past forty years, even though great efforts have been made, there is still much to be done before a safe therapy is achieved [4,5]. Chemotherapy and radiotherapy are still the main therapeutic methods for cancer. Most of the anticancer drugs have toxic side effects. It is critical to develop novel anticancer drugs that have no toxic side effects on other tissues or organs in vivo, and only target the lesion area. Compared with traditional chemotherapeutic drugs, the nano-anticancer drug therapy has potential application prospects in curing cancer diseases [6,7]
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