Formulated nano-liposomes for reversal of cisplatin resistance in NSCLC with nucleus-targeting peptide

Cell membrane-engineered nano-delivery systems have evolved as a promising strategy to enhance drug bioavailability, offering an alternative for reversing drug resistance in cancer therapy. Herein, a formulated nano-liposome that fabricated by hybridizing cisplatin-resistant A549 cell line (A549/cis) cancer cell membrane and phospholipids for co-delivery of cisplatin and nuclear protein zeste homolog 2 (EZH2)-targeting peptide EIP103, referred to as cLCE, was developed. In vitro results indicated that the formulated nano-liposome can efficiently inhibit A549/cis cancer cell invasion and metastasis through the down-regulation of N-cadherin and vimentin proteins. Mechanistic studies demonstrated that the reduction of nerve growth factor receptor (NGFR) levels and the increase of peroxisome proliferator-activated receptor γ (PPARγ) levels achieved by EIP103 may contribute to the reversal of cisplatin resistance. In vivo results demonstrated that the encapsulation of both cisplatin and EIP103 within cLCE leads to increased intratumoral accumulation and prolonged survival in A549/cis cancer-bearing mice as compared to the individual drugs alone. This can be attributed to the enhanced tumor homing capability of cLCE achieved through the presence of inherited membrane proteins derived from A549/cis cells. Taken together, this study may provide a highly promising therapeutic strategy to improve clinical treatments for cisplatin-resistance non-small-cell lung cancer (NSCLC) as well as other malignant cancers.