A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 103 times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-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 (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.
The self-assembled peptide cargo carrier with the ability of probe offered an effective strategy to deliver and track the anticancer drug, cisplatin (DDP) in ovarian cancer cells. This simple peptide system containing a pyrene fluorogen and arginine-glycine-aspartic acid (RGD) sequence could be utilized to release DDP in situ by the specific recognition between an RGD motif and α v β 3 integrin that was over-expressed on ovarian cancer cells. Importantly, we found that the disassembly-triggered peptide nanofibers , PA1, could effectively combine with DDP and release DDP in the cytoplasm with the pyrene fluorescence restoring. Moreover, the peptide cargo carrier efficiently penetrated tumour cells for enhancing therapeutic efficacy. Our system could open the door for the delivery of anticancer drug in cancer-related therapy.
To develop a smart nanovalve on mesoporous silica nanoparticles (MSNs) for biomedical applications, a new type of peptide-functionalized MSN with a plug-gate nanovalve (PGN) was designed for targeted drug release in cancer cells. The outer shell of MSN was functionalized with K8 peptide (octa-lysine sequence) by click chemistry, followed by reacting with citraconic anhydride via α,β-unsaturated bond to prepare negatively charged MSN–K8(Cit). Subsequently, a cationic K8(RGD)2 peptide containing two Arg–Gly–Asp (RGD) sequences for targeting was introduced via electrostatic interaction to the negatively charged surface of MSN–K8(Cit) to form PGN. It was found that, at pH 5.0 (simulating the endo/lysosomal environment), the surface charge of MSN–K8(Cit) could convert from −41 mV to +19 mV due to the hydrolysis of the acid-labile amides in the acidic condition, implying the subsequent electrostatic repulsion to induce opening of the nanovalves and release of anticancer drug, DOX. According to the drug release studies, 79% of DOX was released within 48 h at pH 5.0, while much less DOX was released at pH 6.5 and 7.4. Furthermore, in vitro cellular experiments confirmed that the drug delivery system had enhanced cellular association and cell inhibition effect on αvβ3-positive U87 MG cancerous cells.
危险品化学品经营许可证（带存储）