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Research Article

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

Minxian Li1,2,3, Mei Jiang4, Mengting Chen1,2, Lilusi Ma1,2, Xiaocui Fang1,2( ), Yanlian Yang1,2( ), Chen Wang1,2( )
Key Laboratory for Biological Effects of Nanomaterials and Nanosafety (Chinese Academy of Sciences), Key Laboratory of Standardization and Measurement for Nanotechnology (Chinese Academy of Sciences), and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China
Sino-Danish Center for Education and Research, Sino-Danish College, Beijing 101499, China
Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
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Graphical Abstract

We reported a nano-liposome formulation synthesized by hybridizing cisplatin-resistant A549 cell line (A549/cis) cell membrane with acid-responsive liposomes containing cisplatin & EIP103 (cLCE) to effectively inhibit non-small-cell lung cancer (NSCLC).

Abstract

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.

Keywords

formulated liposometumor homingcisplatin resistancenucleus-peptidecancer therapy

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Nano Research
Volume 16 Issue 11,
November 2023
Pages 12864-12879
DOI: 10.1007/s12274-023-6273-y
Cite this article:
Li M, Jiang M, Chen M, et al. Formulated nano-liposomes for reversal of cisplatin resistance in NSCLC with nucleus-targeting peptide. Nano Research, 2023, 16(11): 12864-12879. https://doi.org/10.1007/s12274-023-6273-y
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Received: 03 September 2023
Revised: 05 October 2023
Accepted: 16 October 2023
Published: 06 November 2023
© Tsinghua University Press 2023
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