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. The constructed cisplatin@GC-pKs in this work demonstrated enhanced anti-tumor activity for lung cancer therapy, as well as a potential treatment strategy for a variety of cisplatin-resistance related malignancies.

We report the efforts to construct active targeting quantum dots using receptor-binding peptide for enhanced detection and migration inhibition of cancer cells. Peptide E5 has specific binding with chemokine receptor 4 (CXCR4), which is a transmembrane G-coupled receptor involved in the metastasis of various types of cancers. E5 was introduced to the surface of CdSe/ZnS quantum dots via biotin-streptavidin interactions. The constructed CXCR4-targeting quantum dots (E5@QDs) was observed to display improved detection sensitivity and significantly enhanced binding affinity for CXCR4 over-expressed cancer cells, and the ability to inhibit cancer cells migration induced by CXCL12.

pLipo-DOX–ICG demonstrates active targeting behavior for delivery and controllable release of chemotherapeutic drugs to CXCR4-overexpressing tumor ccells.

In this review, we try to reflect the recent progress on assembly structures, aggregation behaviors and the cytotoxicity of beta amyloid (Aβ) peptides, which are closely related to the pathogenesis of Alzheimer's disease (AD).Based on these studies, the progress on the regulation mechanism of various nanobiointerfaces in amyloid peptide assembly and aggregation structures is reviewed and discussed, especially the interaction patterns and mechanisms between Aβ peptides and nanomaterials on the molecule level.These progresses could help to deepen the insights of the complex interactions between amyloid peptides and modulators.To study Aβ peptide conformation, assembly mechanism and aggregation process, developing new efficient nanobiointerface modulators is of great importance for the therapeutic strategy evolution.

The characteristics of peptide conformations in both solution and surface-bound states, using poly-glycine as a model structure, are analyzed by using molecular dynamics (MD) simulations. The clustering analysis revealed significant linearization effect on the peptide conformations as a result of adsorption to surface, accompanied by varied adsorption kinetics and energetics. Depending on the inter-peptide interaction characteristics, distinctively different surface-mediated oligomerization modalities, such as antiparallel conformations, can be identified in MD and confirmed by scanning tunneling microscopy (STM) analysis of the assembly structures. These observations are beneficial for obtaining molecular insights of assembling propensity relating to peptide-surface and peptide-peptide interactions.

We have determined the interaction strengths of the common naturally occurring amino acids using a complete binding affinity matrix of 20 × 20 pairs of homo-octapeptides consisting of the 20 common amino acids between stationary and mobile states. We used a bead-based fluorescence assay for these measurements. The results provide a basis for analyzing specificity, polymorphisms, and selectivity of inter-amino-acid interactions. Comparative analyses of the binding energies, i.e., the free energies of association (ΔG A), reveal contributions assignable to both main-chain-related and side-chain-related interactions originating from the chemical structures of these 20 common amino acids. Side-chain-side-chain and side-chain-main-chain interactions are found to be pronounced in an identified set of amino acid pairs that determine the basis of inter-amino-acid recognition.

Understanding the interface of bionanostructures is crucial for novel biomedical applications. In this review, we endeavor to reflect the recent progress on molecular features of interfacial behavior of peptides and the molecular basis for tuning composition and distribution of amino acids at the interfaces. These progresses could help enrich the insights of protein-interface structures at the level of single amino acids.

Sensitive and selective detection of calcium ions (Ca2+) is important since many biological processes are triggered and regulated by the change of Ca2+ concentrations. Here, we develop a new Ca2+ indicator based on peptide-functionalized carbon dots (f-CDs). The synthetic peptide was designed with a hydrophilic head that mimic the Ca2+ binding loop in calmodulin (CaM) protein, and a hydrophobic tail which can form stable interaction with CDs through pi-pi stacking. CDs functionalized with the synthetic peptide can specifically capture Ca2+ ions in biologically relevant media, leading to efficient fluorescence quenching. The quenched fluorescence intensity is linear with the concentration of Ca2+ ions over a wide range, from 5 x 10(-6) to 10(-2) M. Furthermore, cell viability assays show that f-CDs exhibit negligible cytotoxicity to neuroblastoma cells up to a concentration of 50 mu g/mL. These results show that f-CDs are promising for sensitive and selective detection of Ca2+ ions in biological applications.

Surface modification can impart nanostructures new interface properties. In this review, we summarize the representative surface modification methods of nanoparticles with peptides and proteins. The biomolecules can be conjugated with nanoparticles by noncovalent and covalent coupling. Both of these approaches have strengths and limitations. Physical adsorption is the most direct and simplest noncovalent method but peptides and proteins adsorbed on solid surface always loss their native structures and biological activity and the behavior of peptides and proteins on surface is still difficult to regulate precisely. A popular noncovalent conjugation with stability and selectivity is via biotin-streptavidin interaction. Covalent attachment is more stable and selective than noncovalent methods. The stability of covalent biomolecule-nanostructure conjugates makes this strategy useful for applications in biological media with other interfering species. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/ N -hydroxysuccinimide (NHS) strategy is widely used for covalent bioconjugation with well-established protocol, but it could lead to hydrolysis problem, crosslinking and uncontrolled heterogeneous orientation. The click chemistry is another covalent strategy with higher selectivity and yield, while it takes an extended reaction time. In addition to considering stability, selectivity, reaction time, and yield mentioned above, covalent bioconjugation should proceed in mild condition and the reagents required should have no interference on properties of biomolecules and nanostructures. In recent years substantial progress has been made in the formation of bionanoconjugates, but there is still no completely reliable approach for biomolecule-nanosturcture conjugation. Heretofore fine-tuning the structure and orientation of peptides and proteins on surface has been challenging. The efforts on improving biostability, biodistribution and targeting of nanoparticles with peptides and proteins functionalization are introduced. Nanostructures are often used within body in biomedical applications, so they must overcome an ensemble of biological obstacles to perform their function. First they may suffer from clearance from the bodys immune system. Even though they can escape from clearance, they are required to arrive their correct battlefield. Whats more, nanostructures need to cross cell membrane barriers and reach specific organelles such as nucleus and mitochondria to function in most cases. Peptide- and protein-nanostructure conjugation has been emerged as a useful tool to address these problems mentioned above. They could provide nanostrctures protection from phagocytic clearance and promote persistent circulation. Nanostructures can penetrate cell membrane easily with cell-penetrating peptide modification. The specific recognition of biological molecules imparts nanostructures targeting ability. In addition, the applications in fields such as diagnostics are introduced based on antigen-antibody specific recognition. The problems that bionanoconjugates for medical applications may encounter in use are presented briefly. Once contacting with biological matrices, nanostructures will be immediately coated by proteins, forming a protein corona. This protein layer could make significant changes in nanostructure properties such as size, surface charge and even the bioactivity of the peptides and proteins conjugated on its surface, which provides nanostructure with a new biological identity. Some previous results suggested that protein-functionalized nanoparticles lost their targeting capabilities when a protein corona adsorbed on the surface. In short, not only should bioconjugation methods be picked carefully depending on the goals, but also the effects of the complex use environment on bionanoconjugates should be taken into consideration. This review is intended to help researchers get an idea of the progress and dilemma of bionanoconjugate construction and its applications, and provide some inspiration for design and synthesis of peptide and protein-modified nanostructures.

The abnormal accumulation of beta-amyloids (A beta) in brain is considered as a key initiating cause for Alzheimer's disease (AD) due to their richness in plaques and self-aggregate propensity. In recent studies, N-terminally extended A beta peptides (NTE-A beta) with the N-terminus originating prior to the canonical beta-secretase cleavage site were found in humans and suggested to have possible relevance to AD. However, the effects of the extended N-terminus on the amyloidegenic structure and aggregation propensity have not been fully elucidated. Herein, we characterized the assembly structures of A beta 1-42, A beta(-5)-42, A beta(-10)-42 and A beta(-15)-42 with both normal and reversed sequences on highly oriented pyrolytic graphite (HOPG) surfaces with scanning tunneling microscopy (STM). The molecularly resolved surface-mediated peptide assemblies enable identification of amyloidegenic fragments. The observations reveal that the assembly propensity of the C-terminal strand of A beta 1-42 is highly conserved and insensitive to N-terminal extensions. In contrast, different assembly structures of the N-terminal strand of A beta variants can be observed with possible assignment of varied amyloidegenic fragments in the extended N-termini, which may contribute to the varied aggregation propensities of A beta 42 species.

For the design and optimization of functional peptides, unravelling the structures of individual building blocks as well as the properties of the ensemble is paramount. TTR1, derived from human transthyretin, is a fibril-forming peptide implicated in diseases such as familial amyloid polyneuropathy and senile systemic amyloidosis. The functional peptide TTR1-RGD, based on a TTR1 scaffold, was designed to specifically interact with cells. Here, we used scanning tunneling microscopy (STM) to analyze the assembly structures of TTR1-related peptides with both the reverse sequence and the modified forward sequence. The sitespecific analyses show the following: i) The TTR1 peptide is involved in assembly, nearly covering the entire length within the ordered β-sheet structures. ii) For TTR1-RGD peptide assemblies, the TTR1 motif forms the ordered β-sheet while the RGDS motif adopts a flexible conformation allowing it to promote cell adhesion. The key site is clearly identified as the linker residue Gly13. iii) Close inspection of the forward and reverse peptide assemblies show that in spite of the difference in chemistry, they display similar assembling characteristics, illustrating the robust nature of these peptides. iv) Glycine linker residues are included in the β-strands, which strongly suggests that the sequence could be optimized by adding more linker residues. These garnered insights into the assembled structures of these peptides help unravel the mechanism driving peptide assemblies and instruct the rational design and optimization of sequenceprogrammed peptide architectures.

CAS Key Laboratory of Standardization an Key Laboratory of Biological Effects of Nan for Excellence in Nanoscience, National C Beijing 100190, P. R. China. E-mail: wang +86-10-82545561; +86-10-82545559 Academy for Advanced Interdisciplinary Stu R. China Institute of Basic Medical Sciences, Chines Union Medical College, Beijing 100005, P Tel: +86-10-69156437 University of Chinese Academy of Sciences, † Electronic supplementary informa 10.1039/c7ra01735a Cite this: RSC Adv., 2017, 7, 21298

Human serum albumin (HSA) is an abundant protein in plasma that can bind and transport many small molecules, and the corresponding affinity‐controlled drug delivery shows great advantage in the biological system. Peptide SA06 is a reported ligand comprising 20 amino acids, and is known to non‐covalently bind with HSA to extend the lifetime and improve the pharmacokinetic performance. The structural information of the HSA‐peptide complex is keen for obtaining molecular insight of the binding mechanism. We studied the secondary structural change and structure‐affinity relations of Peptide SA06 with HSA by using circular dichroism (CD) spectroscopy in solution. Noticeable allosteric effect can be identified by compositional increase of α‐helix structures when the peptide was co‐incubated with HSA. Furthermore, the equilibrium dissociation constant of Peptide SA06 with HSA can be determined by CD‐based method. This work provides structural evidence on the allosteric interaction between peptide ligand and HSA, and sheds light on optimization of therapeutic properties in the affinity‐controlled delivery systems.

The inside back cover picture shows the allosteric modulation of human serum albumin (HSA) induced by the Peptide SA06 ligand. Peptide SA06 is a reported peptide ligand comprising 20 amino acids, and is known to non‐covalently bind with HSA to extend the lifetime and improve the pharmacokinetic performance of drug molecules. The structural evidence on the allosteric interaction between peptide ligand and HSA, and the structure‐affinity relations of the binding mechanism have been revealed in this work, which can also shed light on optimization of therapeutic properties in the affinity‐controlled delivery systems. More details are discussed in the article by Wang et al. on page 1270–1277. image

A facile method for encapsulation of insoluble drugs has been developed based on the metal ion/polyphenol complexation and aerosol spraying process. The encapsulated paclitaxel nanodrug (PTX-C) is well-controlled in morphology and pH-responsive. In vivo and in vitro experiments demonstrated the enhanced anti-tumour activity of PTX-C. This study may pave the way for the fabrication of low cost, high efficiency drug delivery systems for cancer therapies.

A designed peptide (W4) has a significant inhibitory effect on the CXCL12/CXCR4 axis by targeting CXCL12 with high binding affinity.

Silver nanoparticles (AgNPs) have tremendous potentials in medical devices due to their excellent antimicrobial properties. Blood compatibility should be investigated for AgNPs due to the potential blood contact. However, so far, most studies are not systematic and have not provided insights into the mechanisms for blood compatibility of AgNPs. In this study, we have investigated the blood biological effects, including hemolysis, lymphocyte proliferation, platelet aggregation, coagulation and complement activation, of 20 nm AgNPs with two different surface coatings (polyvinyl pyrrolidone and citrate). Our results have revealed AgNPs could elicit hemolysis and severely impact the proliferation and viability of lymphocytes at all investigated concentrations (10, 20, 40 μg/mL). Nevertheless, AgNPs didn’t show any effect on platelet aggregation, coagulation process, or complement activation at up to ~40 μg/mL. Proteomic analysis on AgNPs plasma proteins corona has revealed that acidic and small molecular weight blood plasma proteins were preferentially adsorbed onto AgNPs, and these include some important proteins relevant to hemostasis, coagulation, platelet, complement activation and immune responses. The predicted biological effects of AgNPs by proteomic analysis are mostly consistent with our experimental data since there were few C3 components on AgNPs and more negative than positive factors involving platelet aggregation and thrombosis.

We present for the first time an enhanced interaction affinity between an abundant soluble protein (human serum albumin) and a membrane protein (chemokine receptor 4) mediated by a dual-affinity peptide E5.