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Leukocyte-Mediated Combined Targeted Chemo and Gene Therapy for Esophageal Cancer

Yali Jun1, Zhuang Tang1, Chao Luo1

  • 1Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, Huai'an 223300, China.

ACS Applied Materials & Interfaces
|September 30, 2020
PubMed

Insights

This study introduces a novel nanovector for esophageal cancer treatment, combining chemotherapy and gene therapy. The leukocyte membrane-coated nanovector effectively targets cancer cells, inhibiting growth and metastasis for improved therapeutic outcomes.

Area of Science:

  • Nanomedicine
  • Oncology
  • Molecular Therapy

Background:

  • Esophageal cancer presents a poor prognosis due to limited treatment efficacy and targeted therapy options.
  • Nanoparticle drug delivery systems offer potential for simultaneous delivery of multiple therapeutic agents in tumor treatment.

Purpose of the Study:

  • To develop a novel nanovector for targeted combination gene therapy and chemotherapy in esophageal cancer.
  • To investigate the efficacy of a leukocyte membrane-coated nanovector carrying doxorubicin and siLPCAT1.

Main Methods:

  • A novel lipid nanovector (EYLN) was engineered to encapsulate doxorubicin (Dox) and small interfering RNA targeting LPCAT1 (siLPCAT1).
  • The nanovector EYLN-Dox/siLPCAT1 was coated with leukocyte membranes to create mEYLNs-Dox/siLPCAT1.
  • Characterization of particle size (~136 nm) and zeta potential (-21.18 mV) was performed.
  • In vitro and in vivo studies assessed cellular internalization, proliferation, migration, metastasis inhibition, and tumor suppression.

Main Results:

  • Leukocyte membrane coating enhanced cellular internalization of the nanovector by esophageal cancer cells.
  • mEYLNs-Dox/siLPCAT1 significantly inhibited esophageal cancer cell proliferation, migration, and metastasis, alongside LPCAT1 expression.
  • The nanovectors demonstrated improved blood circulation, tissue distribution, tumor targeting, and tumor suppression in a mouse model.
  • Combination therapy via the nanodelivery system showed superior therapeutic efficacy compared to non-coated vectors.

Conclusions:

  • The developed leukocyte membrane-coated nanovector (mEYLNs-Dox/siLPCAT1) represents a promising strategy for targeted combination gene and chemotherapy in esophageal cancer.
  • This approach enhances drug delivery, leading to significant inhibition of tumor progression and improved therapeutic outcomes.
  • Further development of this nanodelivery system could offer a new therapeutic avenue for esophageal cancer treatment.
Keywords:
LPCAT1esophageal cancergene therapyleukocytenanovector

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