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20– 22 Among these, pH-induced charge reversal and pH-sensitive transmembrane insertion of a low-pH insertion peptide have also been explored as novel strategies to increase the efficacy of biomaterial administration.
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For example, the development of acid-activated CPPs takes advantage of the acidic tumour extracellular environment 18, 19 for tumour-targeted drug delivery. An alternative strategy to selectively enhance cell–material interfacing lies in the design of smart systems that are triggered by external stimuli, or specific features of the target cell or local tissue physiology. 16, 17 In spite of their potential, the inherent non-specificity of CPPs has restricted their application in targeted delivery systems. 8, 9 In addition, new cell-penetrating transporters have been developed such as synthetic peptides, 10, 11 helical poly(arginine) mimics, 12 antibiotics, 13 poly-(disulfide)s 14, 15 and guanidinium-containing synthetic polymers. Cell-penetrating peptides (CPPs) such as the HIV transactivator of transcription (TAT) peptide and arginine oligomer protein-transduction domain have been widely used as transport vector tools for the cellular import of a variety of cargos ( e.g., nanomaterials and biomolecules) through the cell membrane. Amongst the main hurdles, the hydrophobic nature of the lipid bilayer of the plasma membrane renders it impermeable to most polar, hydrophilic molecules including peptides, proteins, oligonucleotides, drugs and nanomaterials that lack specific membrane receptors or transport mechanisms. 1– 7 However, further translation beyond basic research is heavily hampered by the inefficient performance of nanomaterials in biological environments. The recent explosive growth of research in the field of nanotechnology has provided a wide range of novel materials and strategies for biomedicine, including important advances in bioimaging, drug delivery, photothermal/photodynamic therapy, and gene transfection. We anticipate that the innovative approach proposed in this work will help to establish new stimuli-responsive delivery systems and biomaterials. Furthermore, we show light-controlled cell adhesion on a peptide-modified surface and 3D spatiotemporal control over cellular uptake of nanoparticles using two-photon excitation. Using this system, we can remotely regulate drug administration into cancer cells by functionalizing camptothecin-loaded polymeric nanoparticles with our synthetic peptide ligands. When the peptide is conjugated to ligands of interest, we demonstrate the photo-activated cellular uptake of a wide range of cargoes, including small fluorophores, proteins, inorganic ( e.g., quantum dots and gold nanostars) and organic nanomaterials ( e.g., polymeric particles), and liposomes. To achieve this, we designed a novel photo-caged peptide which undergoes a structural transition from an antifouling ligand to a cell-penetrating peptide upon photo-irradiation.
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Here we report new photo-activatable cell–material interfacing systems that trigger cellular uptake of various cargoes and cell adhesion towards surfaces. Spatio-temporally tailoring cell–material interactions is essential for developing smart delivery systems and intelligent biointerfaces.