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“Transformation” to Help Treat Tumor

Tumor has long been the thorn in the flesh for both patients and doctors, but enhanced cellular internalization of tumor plays a significant role in its treatment. Prof. Han Heyou of HZAU applied the ingenious idea to his study. By combining tumor microenvironment with transformation of the shape of nanoparticles, which switch from spherical to rod-like shape triggered by tumor extracellular acidic microenvironment, photodynamic therapy is enhanced.

Some microorganisms in nature with rod-like shape exhibit powerful infection capability to animal cells. Studies inspired by this found out that, compared with spherical nanoparticles, rod-like ones with certain length-diameter ratio can accelerate cellular internalization, which demonstrate better performance when entering cells. However, rod-like nanoparticles always fail to discern tumor cells from healthy ones and the applicability in tumor selective therapeutics is scarcely reported.

Overproliferation and incomplete glycolysis of tumor cells result in an accumulation of lactic acid, thus creating a tumor extracellular acidic microenvironment. Prof. Han and his team, by combining such acidity with geometric shape switch of nanomaterial, designed an acidity-responsive chimeric peptide with geometrical shape switch. In the process of blood circulation, polypeptides self-assembly into spherical nanoparticles, which facilitates the arrival and concentration of these particles in tumor region by enhancing permeability and retention effect. Once arriving, tumor extracellular acidity initiated detachment of dimethylmaleic anhydride (DMA) groups. Recovered ionic complementarity together with hydrogen bonding, and hydrophobicity mediated the formation of short rod-like nanoparticles. Researches on animal cells manifested that the sphere-to-rod switch can boost the targeted concentration of nanoparticles at tumor tissues. More importantly, the sphere-to-rod switch has significantly increased cellular internalization of nanomaterial. Therefore photodynamic therapy is enhanced and toxic and side effects are remarkably reduced. This research results has provided new insights into the design of targeted drug delivery.

Recently, ACS Nano (a well-known chemical journal) published online the research results of Prof. Han’s team (Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy). Associate research fellow Han Kai is the first author and Prof. Han is the corresponding author. The research was funded by National Natural Science Foundation of China (51603080,21375043), National Key R&D Plan and State Key Laboratory of Agricultural Microbiology.


(By Lei Xue)