We report a new peptidyl boronic acid-based fluorescent probe with an aggregation-induced emission (AIE) characteristic. Through specific recognition between the boronic acid group and the cancer-associated sialic acid (SA), this fluorescent probe shows an ability for targeted labelling and imaging of cancer cells.

•Two functional peptides (TCPP and TPP) were designed and synthesized.•Highly controllable MSNs were prepared by using TCPP and TPP as gatekeepers.•The newly developed MSNs show a remarkable synergistic anticancer effect.Synergistic therapy involving two or more therapeutic agents with different anticancer mechanisms represents a promising approach to eradicate chemotherapy-refractory cancers. However, the preparation of a synergistic therapy platform generally involves complicated procedures to encapsulate different therapeutic agents and thereby increases the purification difficulty. In this work, we reported a simple but robust strategy to prepare a highly controllable drug delivery system (DDS) for synergistic cancer therapy. To construct this robust DDS, mesoporous silica nanoparticles (MSNs) were employed as a nanoplatform to encapsulate anticancer drug doxorubicin (DOX). After using a tumor-targeting cellular membrane-penetrating peptide (TCPP) and a mitochondria-targeting therapeutic peptide (TPP) to seal the surface pores via disulfide bonds, these newly developed MSNs can target cancer cells, penetrate cell membrane and rapidly release anticancer drug and mitochondria-targeted peptide in cytoplasm, inducing a remarkable synergistic anticancer effect. The new design concept reported here will promote the development of targeted and smart DDSs for synergistic cancer therapy.

We report a new tumor-targeting amphiphilic peptide that can form complementary hydrogen bonds with anti-tumor drug methotrexate (MTX), leading to reversible self-assembled morphology transition from loose micelles to densely packed nanorods or nanofibers. The MTX loaded nanorods can target tumor cells and show more than 2-fold higher cytotoxicity (IC50 = 0.38 mg L−1) than that towards normal cells (IC50 = 0.89 mg L−1).

A new multi-functional amphiphilic fusion (MFAF) peptide comprised of a multi-functional fusion peptide sequence (GFLGR8GDS) and a hydrophobic polycaprolactone (PCL) tail was designed and prepared. In aqueous solution, through the strong hydrophobic interaction among the PCL tails, this MFAF peptide can self-assemble into core–shell micelles at a low concentration with the anti-tumor drug doxorubicin (DOX) loaded in the core and the multi-functional fusion peptide sequence located on the shell. When incubating the DOX-loaded micelles with tumor and normal cells, the micelles can use the RGD and membrane-penetrating peptide (eight continuous arginine residues, R8) sequences to target tumor cells and penetrate cell membranes. Subsequently, cathepsin B, an enzyme over-expressed in late endosomes and lysosomes of tumor cells that can specifically hydrolyze the GFLG sequence, can break the micellar structure and lead to a rapid release and escape of loaded DOX from endosomes, resulting in the apoptosis of tumor cells. The MFAF peptide presents great potential as a new drug delivery platform for targeted cancer chemotherapy.

•A new amphiphilic peptide was designed and prepared.•The amphiphilic peptide can self-assemble into spherical micelles with size of 30 nm.•The self-assembled micelles show an acid-responsive drug release behavior.•The self-assembled micelles can targetedly deliver doxorubicin into tumor cells.An acid-responsive amphiphilic peptide that contains KKGRGDS sequence in hydrophilic head and VVVVVV sequence in hydrophobic tail was designed and prepared. In neutral or basic medium, this amphiphilic peptide can self-assemble into micelles through hydrogen bonding and hydrophobic interactions. If changing the solution pH to an acidic environment, the electrostatic repulsion interaction among the ionized lysine (K) residues will prevent the self-assembly of the amphiphilic peptide, leading to the dissociation of micelles. The anti-tumor drug of doxorubicin (DOX) was chosen and loaded into the self-assembled micelles of the amphiphilic peptide to investigate the influence of external pH change on the drug release behavior. As expected, the micelles show a sustained DOX release in neutral medium (pH 7.0) but fast release behavior in acidic medium (pH 5.0). When incubating these DOX-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD sequence to deliver the drug into HeLa cells. Combined with the low cytotoxicity of the amphiphilic peptide against both HeLa and COS7 cells, the amphiphilic peptide reported in this work may be promising in clinical application for targeted drug delivery.

We report a new tumor-targeting amphiphilic peptide that can form complementary hydrogen bonds with anti-tumor drug methotrexate (MTX), leading to reversible self-assembled morphology transition from loose micelles to densely packed nanorods or nanofibers. The MTX loaded nanorods can target tumor cells and show more than 2-fold higher cytotoxicity (IC50 = 0.38 mg L−1) than that towards normal cells (IC50 = 0.89 mg L−1).