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Chinese Scientists Give New Inspirations on the Design of Efficient Drug Delivery Nanoparticles
Update time: 2018-09-18
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Nanoparticle-based drug delivery systems have brought promising results in the past few decades due to their capabilities of improving the bioavailability and reducing the side effects through target delivery.

To date, however, the multiple biological barriers encountering by the nanoparticles still significantly limit their potency of drug delivery. Therefore, rational engineering of particle characteristics to efficiently transport across those barriers has been in urgent need.

Recently, Prof. GAN Yong’s group from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences co-worked with Prof. SHI Xinhua’s group from the National Center for Nanoscience and Technology, provide deep insight into the effect of mechanistic properties of nanoparticle-based drug delivery systems on overcoming multiple biological barriers. The finding was published online in Nature Communications.

In their previous work, they revealed the rotational and hopping movement patterns of rod-shaped nanoparticles diffusing in intestinal mucus, which exhibited superiority over conventionally used spherical particles, and could therefore enhance the oral absorption of drugs.

While noticing the significance of this physical property, researchers have come to realize the similarities in mucosal tissue and tumor, both of which require the nanoparticles to rapidly penetrate a layer of mesh-like, adhesive bio-hydrogel (mucus and tumor extracellular matrix).

Such phenomenon gives inspirations that some universal disciplines can be developed based on mechanistic principles for the design of nanoparticles for mucosal and tumor delivery.

In this work, microfluidics is adopted to fabricate nanoparticles with tunable rigidity. The nanoparticles are composed of liposome-based shell and poly(lactic-co-glycolic acid) (PLGA)-based core.

They discover that semi-elastic nanoparticles have the highest diffusivities in both intestinal mucus and tumor spheroid, overwhelming the hard or soft counterparts. The rapid permeation can therefore result to their enhanced cellular uptake and tumor accumulation.

By means of stimulated emission depletion (STED) microscopy and molecular simulation techniques, they elucidate the underlying mechanism that the deformation capacity of nanoparticles can significantly influence their permeability.

Soft nanoparticles are more likely to deform and easily adhere to the mucin, while hard nanoparticles are readily to be trapped in the mesh-structured bio-hydrogels.

Nanoparticles with medium elasticity can diffuse rapidly via appropriate deformation. They can effectively escape from adhesive interactions. Further studies proved the delivery efficiency of those semi-elastic nanoparticles.

These findings offer fundamental guidelines for the engineering of physical properties such as shape, and the mechanism of designing nanoparticles for mucosal and tumor delivery.

This work was supported by the National Natural Science Foundation of China, the Strategic Priority Research Program of Chinese Academy of Sciences, National Center for Protein Science Shanghai and Instrumental Analysis Center of Shanghai Jiao Tong University.

Original article link:

Figure: Semi-elastic nanoparticles can efficiently penetrate the mucosal tissue and tumor matrix compared to the soft and hard nanoparticles. (Image by YANG Yiwei)

Contact person:
Prof. GAN Yong

(Credit: YANG Yiwei; Editor: PAN Peihua)




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