Enzyme-Responsive Amphiphilic Peptide Nanoparticles for Biocompatible and Efficient Drug Delivery

Self-assembled peptide nanostructures recently have gained much attention as drug delivery systems. As biomolecules, peptides have enhanced biocompatibility and biodegradability compared to polymer-based carriers. We introduce a peptide nanoparticle system containing arginine, histidine, and an enzyme-responsive core of repeating GLFG oligopeptides. GLFG oligopeptides exhibit specific sensitivity towards the enzyme cathepsin B that helps effective controlled release of cargo molecules in the cytoplasm. Arginine can induce cell penetration, and histidine facilitates lysosomal escape by its buffering capacity. Herein, we propose an enzyme-responsive amphiphilic peptide delivery system (Arg-His-(Gly-Phe-Lue-Gly)3, RH-(GFLG)3). The self-assembled RH-(GFLG)3 globular nanoparticle structure exhibited a positive charge and formulation stability for 35 days. Nile Red-tagged RH-(GFLG)3 nanoparticles showed good cellular uptake compared to the non-enzyme-responsive control groups with d-form peptides (LD (LRH-D(GFLG)3), DL (DRH-L(GFLG)3), and DD (DRH-D(GFLG)3). The RH-(GFLG)3 nanoparticles showed negligible cytotoxicity in HeLa cells and human RBCs. To determine the drug delivery efficacy, we introduced the anticancer drug doxorubicin (Dox) in the RH-(GFLG)3 nanoparticle system. LL-Dox exhibited formulation stability, maintaining the physical properties of the nanostructure, as well as a robust anticancer effect in HeLa cells compared to DD-Dox. These results indicate that the enzyme-sensitive RH-(GFLG)3 peptide nanoparticles are promising candidates as drug delivery carriers for biomedical applications.

PREDICTION OF BONDING ENERGY BY STRUCTURAL DESCRIPTORS OF METAL NANOALLOYS

Обсуждается проблема предсказания энергии связи для тернарных металлических наночастиц и построение моделей обучения на базе структурных дескрипторов. Были построены регрессионные зависимости удельной межатомной энергии связи для тернарной наносистемы Au - Ag - Cu. Использовался ряд из пяти радиальных признаков, зависящих от попарного межатомного расстояния дескрипторов структуры наночастицы. Для более корректной оценки точности была применена кросс-валидация, далее полученные на валидационных частях выборки результаты усреднялись. Полученная модель ограниченно предсказывает значение удельной межатомной энергии связи внутри группы данных для наночастиц одного состава, а для всей выборки средняя по модулю ошибка составляет 14%. При этом модель практически безошибочно определяет состав наночастицы из нескольких вариантов. Наибольшее значение коэффициента детерминации на всей выборке получено с помощью ансамблевого алгоритма случайный лес. Обнаружена отрицательная корреляция между энергией связи наносплава и положением первого пика радиальной функции распределения для атомов меди. The problem of predicting the binding energy for ternary metal nanoparticles and the construction of learning models based on structural descriptors are discussed. Regression dependences of the specific interatomic bond energy were constructed for the ternary Au - Ag - Cu nanosystem. A number of five radial features were used, depending on the pairwise interatomic distance of the nanoparticle structure descriptors. For a more correct assessment of the accuracy, cross-validation was applied, then the results obtained on the validation parts of the sample were averaged. The resulting model limitedly predicts the value of the specific interatomic binding energy within a group of data for nanoparticles of the same composition. For the entire sample the average error in modulus is 14 %. In this case, the model almost accurately determines the composition of a nanoparticle of several variants. The largest value of the coefficient of determination in the entire sample was obtained using an ensemble random forest algorithm. A negative correlation was found between the binding energy of the nanoalloy and the position of the first peak of the radial distribution function for copper atoms.

A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism

In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparticles mainly composed of an anticancer drug of PEM (PEM-FFRGD) were prepared to deliver PEM to tumors. The peptide could self-assemble into a nanoparticle structure with diameter of about 20 nm. Moreover, the nanoparticle showed favorable solubility and biocompatibility compared with those of PEM, and the MTT test on A549 and LLC cells showed that the PEM-FFRGD nanoparticles had stronger cytotoxic activity than PEM alone. Most importantly, the nanoparticle could promote tumor apoptosis and decrease mitochondrial energy metabolism in tumors. In vivo studies indicated that PEM-FFRGD nanoparticles had enhanced antitumor efficacy in LLC tumor-bearing mice compared to that of PEM. Our observations suggested that PEM-FFRGD nanoparticles have great practical potential for application in lung cancer therapy.

Study of Electrokinetic Properties of Magnetite – Silica Core – Shell Nanoparticles

In this work, the electrokinetic properties of Fe3O4 nanoparticles modified with various alkoxysilanes (tetraethoxysilane and 3-aminopropyltriethoxysilane) in various media were investigated. The determined values of the zeta potential of the Fe3O4/SiO2 samples indicate the complete coverage of nanoparticles with a tetraethoxysilane shell, as well as in the case of the Fe3O4/aminopropyltriethoxysilane. The data obtained on the zeta-potentials of modified nanoparticles with various ligands make it possible to predict the efficiency of subsequent functionalization by target molecules. A decisive role in the study of surface properties is played by cleaning from low molecular weight impurities that can screen the surface of nanoparticles or bind with an indifferent electrolyte. Thus, dispersion on a magnetic stirrer leads to an increase in the sorption capacity of the sample in comparison with ultrasonic dispersion, which causes irreversible destruction of the core-shell nanoparticle structure due to an increase in temperature and pressure in the cavities. This opens the prospective for practical application of modified nanoparticles for creation of tailored composite materials.

Lipid Nanoparticle Technology for Delivering Biologically Active Fatty Acids and Monoglycerides

There is enormous interest in utilizing biologically active fatty acids and monoglycerides to treat phospholipid membrane-related medical diseases, especially with the global health importance of membrane-enveloped viruses and bacteria. However, it is difficult to practically deliver lipophilic fatty acids and monoglycerides for therapeutic applications, which has led to the emergence of lipid nanoparticle platforms that support molecular encapsulation and functional presentation. Herein, we introduce various classes of lipid nanoparticle technology and critically examine the latest progress in utilizing lipid nanoparticles to deliver fatty acids and monoglycerides in order to treat medical diseases related to infectious pathogens, cancer, and inflammation. Particular emphasis is placed on understanding how nanoparticle structure is related to biological function in terms of mechanism, potency, selectivity, and targeting. We also discuss translational opportunities and regulatory needs for utilizing lipid nanoparticles to deliver fatty acids and monoglycerides, including unmet clinical opportunities.

Optical Analysis of Hole Patterned Ag Nanoparticle Structure

A structure with periodic sub-wavelength nanohole patterns interacts with incident light and causes extraordinary optical transmission (EOT), with metal nanoparticles leading to localized surface plasmon resonance (LSPR) phenomena. To explore the effects of metal nanoparticles (NPs), optical analysis is performed for metal NP layers with periodic hole patterns. Investigation of Ag NP arrangements and comparisons with metal film structures are presented. Ag NP structures with different hole configuration are explored. Also, the effects of increasing light incident angle are investigated for metal NP structures where EOT peak at 460 nm wavelength is observed. Moreover, electric field distributions at each transmittance peak wavelengths and optical noise are analyzed. As a result, optical characteristics of metal NP structures are obtained and differences in resonance at each wavelength are highlighted.

Mechanism studies on the cellular internalization of nanoparticles using computer simulations: A review

Nanomaterial drug delivery systems have become one of the most important targeted therapy technologies. Although great efforts have been made to study the self-assembled mesoscopic structure of nanoparticles and understand drug loading and release mechanisms, the interaction between nanoparticles and cell membranes has not yet been clearly studied. Moreover, the research of experimental methods in this field has been greatly restricted due to its special time-space scale, so it is necessary to apply computer simulations to visualize the cell internalization of the nanoparticle. This review covers modelling methods and the current status and viewpoints of research on the influencing factors of the nanoparticle-biomembrane interaction mechanism. In particular, we discussed in detail the positive and negative effects of various nanoparticle properties. This article may assist researchers in rationally optimize the nanoparticle structure to improve therapeutic efficiency.

Enhanced Antibacterial activity of eugenol loaded m-PEG/PCL nanoparticles in eliminating resistant bacteria from wastewater

In this study, eugenol loaded m-PEG/PCL nanoparticles were used to make better the anti-bacterial properties of eugenol in an attempt to eliminate the resistant bacteria. m-PEG/PCL copolymer was prepared by ring-opening polymerization of ε-caprolactone monomer in the vicinity of dry m-PEG and tin (II) octoate catalyst. Polymeric nanoparticles were prepared by nanoprecipitation procedure. The particle size and zeta potential of mPEG/PCL/eugenol were specified to be 157.23 ± 3.81 nm and − 6.95 ± 0.19 mv, respectively. The polymeric nanoparticle structure was identified by AFM, FT-IR, and DSC techniques. To evaluate and compare the anti-bacterial efficiency of m-PEG/PCL/eugenol and free eugenol, a turbidity assay was used in association with gram-positive and gram-negative bacteria. Images of SEM were taken from bacteria before and after exposure to the mPEG/PCL/eugenol. Colony-forming unit per milliliter (CFU/ml) method was considered to follow the effect of mPEG/PCL/eugenol on bacteria growth rate in the original hospital wastewater. The results showed that m-PEG/PCL/eugenol nanoparticles at 40 µM concentration show the enormous antibacterial effect at 37°C. In original hospital wastewater, m-PEG/PCL/eugenol in the concentration of 0.125 µM at 25 ° C showed the greatest growth decrease of microbial total count.