In Vivo Structrual Modulation Of Bis-pyrene Based Nanomaterials For Inhibition Of Tumor Metastasis

Nanotechnology and the emerging of nanomedicine provides a powerful weapon for cancer therapy.The peptide nano-drugs can elevate therapeutic of drugs through longer retention time in the body and specific accumulation at tumor sites via en-hanced permeability and retention?EPR?effect.Herein,inspired by the formation of natural ECM and the in situ self-assembly strategy developed in our group,herein,we in situ constructed an artificial extracellular matrix?AECM?based on transformable Laminin?LN?-mimic transformable nanomaterials?Peptide 1:BP-KLVFFK-GGDGR-YIGSR?for inhibition of tumor invasion and metastasis.Firstly,we synthesized an AIE effect fluorescent molecular BPCOOH,which can efficient coupling with polypeptide amino acids,as a strong hydrophobic core.At the same time,the aggregation-induced enhanced emission characterization of nano-materials self-assembly process.Secondly,the transformable nanomaterials synthesized by a standard method of solid phase peptide synthesis.The structural transformation of from 1-NPs to 1-NFs by Ca²⁺stimulation was unambiguously confirmed in solution by transmission elec-tron microscope?TEM?and dynamic light scattering?DLS?studies.Moreover,similar structural changes were also observed by co-culture of 1-NPs with cancer cells by variable techniques such as confocal laser scanning microscope?CLSM?and scanning electron microscope?SEM?.To evaluate the inhibition effect of 1-NPs for tumor inva-sion and metastasis,a series of experiments including wound healing,transwell mi-gration and invasion assays were performed.At last,Balb/c nude mice with MDA-MB-231 cell or B16-F10 cell tumors inoc-ulated on their right side of the chest were used in our experiments,which was moni-tored by fluorescence imaging in vivo imaging system to identify the frequency of administration of 1-NPs for inhibition of tumor invasion and metastasis.It is proved that the accumulated 1-NPs simultaneously transformed into nanofibers?1-NFs?around the solid tumor and further entwined to form AECM upon binding to receptors on the tumor cell surfaces.Therefore,this in situ bio-inspired construction of AECM showed great potential for inhibition of tumor invasion and metastasis,which was de-served to be further studied for tumor therapy as a complementary method of chemo-therapy,physiotherapy,photodynamic therapy.