Targeted Delivery of Secretory Promelittin via Novel Poly(lactone-co -β-amino ester) Nanoparticles for Treatment of Breast Cancer Brain Metastases

Advanced Science
Yu ZhouJiangbing Zhou

Abstract

Breast cancer brain metastases (BCBM) is a devastating disease with dismal prognosis. Although chemotherapy is widely used for clinical management of most tumors, it is often ineffective for BCBM. Therefore, alternative approaches for improved treatment of BCBM are in great demand. Here, an innovative gene therapy regimen is reported that is designed for effective treatment of BCBM. First, poly(lactone-co-β-amino ester) nanoparticles that are capable of efficient gene delivery are synthesized and are engineered for targeted delivery to BCBM through surface conjugation of AMD3100, which interacts with CXCR4 enriched in the tumor microenvironment. Next, an artificial gene, proMel, is designed for the expression of secretory promelittin protein, which has limited toxicity on its own but releases cytolytic melittin after activation by MMP-2 accumulated in tumors. It is demonstrated that delivery of the proMel via the AMD3100-conjugated nanoparticles effectively inhibits tumor progression in a BCBM mouse model. This study suggests a new direction to treat BCBM through targeted delivery of promelittin-mediated gene therapy.

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Citations

Aug 25, 2020·Expert Opinion on Drug Delivery·Anabel SorollaValentín Ceña
Jan 16, 2021·Drug Discovery Today·Bilal Ahamad ParayMohammad Z Ahmed
Apr 14, 2021·ACS Applied Materials & Interfaces·Jie ZhouHonglin Jin
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Jul 8, 2021·Macromolecular Bioscience·Víctor HevillaMarta Fernández-García
Oct 31, 2021·Drug Delivery and Translational Research·Christine P CarneyAnthony J Kim
Nov 11, 2021·Nanoscale·Zhihuan LiaoShuaidong Huo

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Methods Mentioned

BETA
transfection
transfects
xenografts
nanoprecipitation
transmission electron microscopy
dynamic light scattering
flow cytometry
Assay
protein assay

Software Mentioned

ImageJ
IVIS
Empower II GPC
GraphPad Prism

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