Original ArticleA drug-delivery strategy for overcoming drug resistance in breast cancer through targeting of oncofetal fibronectin

A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers. We constructed EDB-specific aptide (APTEDB)-conjugated liposome to simultaneously deliver siRNA(siMDR1) and Dox to drug-resistant breast cancer cells. APTEDB-LS(Dox,siMDR1) led to enhanced delivery of payloads into MCF7/ADR cells and showed significantly higher accumulation and retention in the tumors. While either APTEDB-LS(Dox) or APTEDB-LS(siMDR1) did not lead to appreciable tumor retardation in MCF7/ADR orthotropic model, APTEDB-LS(Dox,siMDR1) treatment resulted in significant reduction of the drug-resistant breast tumor. Taken together, this study provides a new strategy of drug delivery for drug-resistant cancer therapy.

Graphical AbstractA novel multi-drug resistance cancer therapy - EDB targeting liposome simultaneously encapsulating MDR-1 siRNA and doxorubicin for targeted, co-delivery of drug for the treatment of drug resistant breast cancer.170