Cellular Trafficking And Biological Effects Of Functional Nanoparticles Modified With Peptides

With the rapid development of nanotechnology, multifunctional nanoparticles promises versatile approaches for enhanced bio-imaging, nano carrier-assisted drug delivery and theranostic treatment in clinical applications. The intracellular behaviors of nanoparticles are fundamentally important for the evaluation of their biosafety and the designs of nano carrier-assisted drug delivery with high therapeutic efficacy. It is fundamentally critical to investigate the delivery mechanism of the nanoparticles crossing various biological barriers including cell membranes, their behaviors of intracellular trafficking, and their final fates thereof. However, little is known regarding how the nanoparticles are translocated from one type of cell organelles to another different type inside the cells. It remains a great challenge to understand the interactions between the biological effects induced by nanoparticles and their metabolism accompanying the host cell responses during their intracellular trafficking.Here we report a new understanding of the interactions between nanoparticles and cells by the development of polyoxometalates nanoparticle-peptide conjugates and investigation of their intracellular trafficking behaviors. The as-prepared nanoparticles are featured with a unique combination of fluorescence and high contrast for synchrotron X-ray diffraction-based imaging. Functional surface modification with peptides facilitates effective delivery of the nanoparticles onto mitochondria as the target and subsequent intracellular trafficking in a dynamic mode. Interestingly, our data have revealed that autophagy of mitochondria(mitophagy) can be induced by NP-peptide as a cellular response for recycling the damaged organelles, through a molecular pathway associated with the change of mitochondrial membrane potential.The biological effects induced by NP-peptide reciprocally affect the distribution patterns and fates of nanoparticles in the cell metabolism by providing an alternative route of intracellular trafficking. The new understanding of the mutual activities between nanoparticles and cells will enrich our approaches in the development of nanobiotechnology and nano-medicine for human healthcare.