Nanomaterials have broad biomedical applications. Although their physicochemical properties such as shape, size, elasticity and surface chemical composition are known to be pivotal in the design of nanomedicines. The impact of dynamic topographical structure of nanomaterials has not attracted significant attention. In this talk, I will show the importance of this new parameter for nanomedicine design. We have found that nanomaterials blood circulation time could be dramatically extended by controlling the dynamic topographical structure of polyethylene glycol (PEG) shell on nanoparticles. Regular high density PEG shell does not have this effect. Previous studies of long circulating nanomaterials all focused on reducing nanoparticle uptake by macrophages. Surprisingly, our studies reveal that the dynamic effect extends nanoparticle blood circulation through a new mechanism, which does not involve macrophages. One of the major challenges of nanomedicines in cancer therapy is the inefficient diffusion of drug nanocarriers in solid tumors due to the high density of extracellular matrix in tumors. One old strategy is to conjugate matrix degrading enzymes on nanoparticle surfaces as the enzymes remove barriers for nanoparticle diffusion. However, successful animal studies have not been demonstrated. One reason is the conjugation of bioactive molecules on nanoparticle surfaces often reduces their blood circulation. We show that the problem can be circumvented by embedding matrix degrading enzymes in the PEG shell with dynamic structure instead of presenting the enzymes on the outmost surface of nanoparticles. The effects of prolonged nanoparticle blood circulation and enhanced diffusion in solid tumors dramatically enhanced nanoparticle accumulation and penetration in tumors, leading to a highly efficient antitumor efficacy. Thus, our platform technology of controlling topographical structure of nanocarriers may be valuable to enhance the clinical efficacy of a broad range of drug nanocarriers.<br/>

Dynamic topographical structure: A new parameter for designing nanomedicine

256th National Meeting (2018)

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