Position-Regulated Electrostatic Interactions for Single Amino Acid Revealed by Aspartic Acid-Scanning Mutagenesis.

We have examined in this contribution the electrostatic interactions between single arginine and aspartic acid by analyzing the peptide-peptide binding characteristics involving arginine-aspartic acid, arginine-glycine, arginine-tryptophan and tryptophan-glycine interactions. The results of aspartic acid mutagenesis revealed that the interactions between arginine and aspartic acid have significant dependence on the position and composition of amino acids. While the primary interaction can be attributed to arginine-tryptophan contacts originated from the indole moieties with the main chains of 14-mers containing N-H and C=O moieties, pronounced enhancement could be identified in association with the electrostatic side-chain-side-chain interactions between arginine and aspartic acid.

Ultrasound-nanovesicles interplay for theranostics.

Nanovesicles (NVs) are widely used in the treatment and diagnosis of diseases due to their excellent vascular permeability, good biocompatibility, high loading capacity, and easy functionalization. However, their yield and in vivo penetration depth limitations and their complex preparation processes still constrain their application and development. Ultrasound, as a fundamental external stimulus with deep tissue penetration, concentrated energy sources, and good safety, has been proven to be a patient-friendly and highly efficient strategy to overcome the restrictions of traditional clinical medicine.

Peptide-based coacervates in therapeutic applications.

Coacervates are droplets formed by liquid‒liquid phase separation. An increasing number of studies have reported that coacervates play an important role in living cells, such as in the generation of membraneless organelles, and peptides contribute to condensate droplet formation. Peptides with versatile functional groups and special secondary structures, including α-helices, β-sheets and intrinsically disordered regions, provide novel insights into coacervation, such as biomimetic protocells, neurodegenerative diseases, modulations of signal transmission, and drug delivery systems.

A nucleus-targeting peptide antagonist towards EZH2 displays therapeutic efficacy for lung cancer.

EZH2 is an overexpressed nuclear protein associated with relatively poor survival and chemoresistance in lung cancer. In this study, a nucleus-targeting peptide antagonist EIP103 capable of penetrating cell membrane and nuclear envelope was identified, and has high binding affinity towards EZH2 localized in the nucleus of lung cancer cells. To improve the stability and therapeutic efficacy of EIP103, PEG-PE micelle encapsulated EIP103 (M-EIP103) was successfully conducted.

Enhancement of gold-nanocluster-mediated chemotherapeutic efficiency of cisplatin in lung cancer.

A novel delivery system for cisplatin was constructed based on electrostatics-mediated assemblies of gold nanoclusters and PEGylated cationic peptide (cisplatin@GC-pKs). Encapsulated cisplatin in the as-formed micelle like assemblies was observed to demonstrate improved cellar uptake and enhanced chemotherapeutic efficiency in the cisplatin-resistant lung cancer cells. In vivo assays further confirmed that cisplatin@GC-pKs had profound anti-tumor efficiency due to deep penetration and accumulation of nanoscale cisplatin@GC-pKs via the enhanced permeability and retention (EPR) effect at tumor tissues.

Enhanced lymphatic delivery of nanomicelles encapsulating CXCR4-recognizing peptide and doxorubicin for the treatment of breast cancer.

Lymph node metastases in cancer patients are associated with high aggressiveness, poor prognosis, and short survival time. The chemokine receptor 4 (CXCR4)/stroma derived factor 1α (CXCL12) biological axis plays a critical role in the spread of cancer cells. Designing effective delivery systems that can successfully deliver CXCR4 antagonists to lymph nodes, which are rich in CXCR4-overexpressing cancer cells, for controlling cancer metastasis remain challenging.

Synthetic CXCR4 Antagonistic Peptide Assembling with Nanoscaled Micelles Combat Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common adult acute leukemia with very low survival rate due to drug resistance and high relapse rate. The C-X-C chemokine receptor 4 (CXCR4) is highly expressed by AML cells, actively mediating chemoresistance and reoccurrence. Herein, a chemically synthesized CXCR4 antagonistic peptide E5 is fabricated to micelle formulation (M-E5) and applied to refractory AML mice, and its therapeutic effects and pharmacokinetics are investigated.

Modulation of β-amyloid aggregation by graphene quantum dots.

Misfolding and abnormal aggregation of β-amyloid peptide is associated with the onset and progress of Alzheimer's disease (AD). Therefore, modulating β-amyloid aggregation is critical for the treatment of AD. Herein, we studied the regulatory effects and mechanism of graphene quantum dots (GQDs) on 1-42 β-amyloid (Aβ) aggregation.

Correction: Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer.

[This corrects the article DOI: 10.1039/C8RA08526A.].

Correction: Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer.

[This corrects the article DOI: 10.1039/C8RA08526A.].

Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer.

The metastasis of breast cancer is one of the main factors resulting in the high fatality of patients. Although many antagonists have been developed to inhibit the metastasis of breast cancer, their practical application has been limited because of the poor solubility of many chemotherapeutic drugs in the physiological environment. Herein, a complex of E5 peptide antagonist and acetylated PAMAM G5 (P) has been constructed to enhance the solubility of the peptide antagonist.

Physicochemical properties of liposomal modifiers that shift macrophage phenotype.

Liposomes are one of the most widely studied drug carriers due to their relative biocompatibility, lack of immune system stimulation, ability to be cell specific, and serve as a protective drug carrier. Due to several physicochemical properties such as size and charge, liposomes naturally target the phagocytic capabilities of macrophages. In the tumor microenvironment, macrophages strongly influence growth and progression, making them an appealing target for drug delivery.

Improving selective targeting to macrophage subpopulations through modifying liposomes with arginine based materials.

The effects of surface modifications on liposomes using a library of arginine derivatives for improved drug delivery were examined. Both unmodified and modified liposomes were tested for their drug delivery properties and propensity for internalization by macrophages. All materials were characterized by dynamic light scattering (DLS) and zeta potential.