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Research Progress

Scientists Develop Novel Nanosystem for Oxygen-Enhanced Chemotherapy and Photodynamic Therapy

Aug 02, 2018

A research team led by Prof. CAI Lintao at the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences constructed a novel hybrid protein nanoparticle as an oxygen carrier for conquering cancer resistances.  

With targeted delivery of oxygen, chemodrug and photosensitizer by this nanosystem, the oxygen-intervened chemo-phototherapy was achieved with potent efficacy.  

Related work was published in Theranostics with the title "Tumor-targeted hybrid protein oxygen carrier to simultaneously enhance hypoxia-dampened chemotherapy and photodynamic therapy at a single dose". 

The researchers developed a method called "disulfide bond reconstruction" to fabricate the hybrid protein nanoparticle. This nanoparticle can be selectively absorbed by cancer cells of vigorous metabolism, delivering bound oxygen and encapsulating drugs at the same time. 

"Hypoxia is one of the typical microenvironment in most solid tumors. Oxygen supply with the targeted hybrid protein nanoparticle can effectively alter this microenvironment. What follows is the oxygen-induced regulation in gene and protein expressions, which are directly correlated with chemoresistance," said CAI.

In vitro experiment indicated that the expression of P-glycoprotein (causing low chemodrug accumulation) was downregulated to 48% after six hours incubation with hybrid protein nanoparticle. 

The hybrid protein nanoparticle with effective oxygen delivery can also enhance photodynamic therapy simultaneously. With laser triggering the photodynamic reaction, the abundant oxygen in tumor was converted to massive cytotoxic reactive oxygen species, and exhibited enhanced killing effect to tumor. 

This novel nanosystem can realize oxygen-enhanced chemotherapy and photodynamic therapy at the same time. With single-dosed treatment, complete tumor inhibition was observed in 15 days. 

"The hybrid protein nanoparticle have the potential in translational medicine trials. Currently, with optimized but very simple method, those nanoparticles can be produced in large amount. Besides, this versatile nanosystem can be incorporated in other therapeutics in which oxygen delivery is demanded," said CAI.

 

Oxygen supply with the targeted hybrid protein nanoparticle alter microenvironment. (Image by CAI Lintao) 

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