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Cancer-cell-membrane-camouflaged supramolecular self-assembly of antisense oligonucleotide and chemodrug for targeted

Tianbao Chen1,2, Jie Xu1,2, Lijuan Zhu1

  • 1Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200217, China. lijuanzhu@sjtu.edu.cn.

Nanoscale
|January 9, 2023
PubMed

Insights

This study presents a novel nanodrug delivery system combining antisense oligonucleotides (ASOs) and chemotherapy for drug-resistant cancers. Cancer cell membrane-camouflaged nanoparticles effectively target tumors and enhance combined gene and chemotherapies.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • B-cell lymphoma-2 (Bcl-2) proteins are overexpressed in cancers, particularly multi-drug resistant types, and are key regulators of cell death.
  • Antisense oligonucleotides (ASOs) targeting Bcl-2 mRNA combined with chemotherapy offer a promising anticancer strategy.
  • Co-delivery of macromolecular ASOs and small molecule drugs faces challenges, and extraneous carriers can cause immunogenicity.

Purpose of the Study:

  • To develop a targeted nanodrug delivery system for co-delivering Bcl-2 ASOs and mitoxantrone (Mito).
  • To overcome challenges in ASO and chemodrug co-delivery and improve anticancer efficacy.
  • To achieve immune escape and tumor targeting using cancer cell membrane (CCM) camouflage.

Main Methods:

  • Self-assembly of cationic amphiphilic mitoxantrone (Mito) with Bcl-2 ASO into nanoparticles (NP[Bcl-2/Mito]).
  • Size control of nanoparticles by regulating the ASO to Mito ratio.
  • Camouflage of NP[Bcl-2/Mito] with homologous tumor-derived cancer cell membranes (CCMs) to form NP[Bcl-2/Mito]@CCM.

Main Results:

  • NP[Bcl-2/Mito] nanoparticles protected ASOs from degradation and enabled combined gene and chemotherapies.
  • NP[Bcl-2/Mito]@CCM demonstrated immune escape and targeted delivery to tumors.
  • In vitro and in vivo studies confirmed the efficacy of NP[Bcl-2/Mito]@CCM in treating drug-resistant breast tumors.

Conclusions:

  • The developed CCM-camouflaged nanoplatform facilitates targeted co-delivery of ASOs and chemodrugs.
  • This approach offers a promising strategy for combination therapy in drug-resistant tumors.
  • The nanodrug delivery system shows potential for overcoming challenges in cancer treatment.

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