No abstract

Photothermal therapy (PTT) exploits nanomaterials with optimal heat conversion and cellular penetration using near-infrared (NIR) laser irradiation. However, current PTT agents suffer from inefficient heat conversion, poor intracellular delivery, and a high dose of probes along with excessive laser irradiation, causing limited therapeutic outcomes. Here, bumpy Au triangular nanoprisms (BATrisms) are developed for increasing the surface area, improving cell penetration, shifting the absorption peak to the NIR region, and enhancing the photothermal conversion efficiency (∼86%). Further, leucine (L)-and lysine (K)-rich cell-penetrating peptides (LK peptides) were employed to largely improve their cellular uptake efficiency. Importantly, a significant in vivo therapeutic efficacy with LK-BATrisms was demonstrated in a triple-negative breast cancer xenograft mice model. A very small dose of LK-BATrism (2.5 μg Au) was enough to exert antitumor efficacy under very low laser power (808 nm, 0.25 W/cm 2 ), causing minimal tissue damages while very efficiently killing cancer cells.

No abstract

An amphipathic leucine (L) and lysine (K)‐rich α‐helical peptide is multimerized based on helix‐loop‐helix structures to maximize the penetrating activities. The multimeric LK‐based cell penetrating peptides (LK‐CPPs) can penetrate cells as protein‐fused forms at 100–1000‐fold lower concentrations than Tat peptide. The enhanced penetrating activity is increased through multimerization by degrees up to the tetramer level. The multimeric LK‐CPPs show rapid cell penetration through macropinocytosis at low nanomolar concentrations, unlike the monomeric LK, which have slower penetrating kinetics at much higher concentrations. The heparan sulfate proteoglycan (HSPG) receptors are highly involved in the rapid internalization of multimeric LK‐CPPs. As a proof of concept of biomedical applications, an adipogenic transcription factor, peroxisome proliferator‐activated receptor gamma 2 (PPAR‐γ 2), is delivered into preadipocytes, and highly enhanced expression of adipogenic genes at nanomolar concentrations is induced. The multimeric CPPs can be a useful platform for the intracellular delivery of bio‐macromolecular reagents that have difficulty with penetration in order to control biological reactions in cells at feasible concentrations for biomedical purposes.

We have developed a cell penetrating peptide (CPP) system with high selectivity and penetrability at nanomolar concentrations with combination of an HER2-selective affibody, ZHER2:342 (ZHER2), and a dimeric α-helical leucine...

Most of cell penetrating peptides (CPPs) are rich in positively-charged amino acids but the cationic property may provoke possible problems in practical applications. In this study, we carefully substituted the hydrophobic amino acids in the SAP(E) sequence, a rare example of negatively-charged proline-rich CPP, with cysteine for enhancement of cell penetrating activity as well as reversible conjugation of cargo molecules. Most substituents showed almost negligible cell penetrating activity, but a cysteine substituent on the 7th valine (SAP(E)-7C) showed more improved cell penetrating activity than SAP(E). When treated to cells, the negatively-charged SAP(E)-7C exhibited much lower degree of co-localization with acidic endosomes or lysosomes compared to positively-charged TAT. SAP(E)-7C could significantly enhance the PTX efficacy on MDA-MB-231 cells by non-covalent complexation with PTX. As a proofof-concept for covalent conjugation of cargo drugs, mercaptoethanol, a model drug, was conjugated to the cysteine residue of SAP(E)-7C via a disulfide bond, and the glutathione-dependent release from the conjugate was confirmed. The negativelycharged SAP(E)-7C with a cysteine handle can be a useful molecular module for the development of CPP-based drug delivery carrier.

In this study, we propose a reversible covalent conjugation method for peptides, proteins, and even live cells based on specific recognition between natural amino acid sequences. Two heptad sequences can specifically recognize each other and induce the formation of a disulfide bond between cysteine residues. We show the covalent bond formation and dissociation between peptides and proteins in cell-free conditions and on the surface of live cells. Because heptad sequences consist of natural amino acids, they are expressed in cells without additional preparation and can be used to selectively conjugate peptides, proteins, and cells.