Nanomaterials For Biomedical Applications Research Articles

Light Responsive DNA Nanomaterials and Their Biomedical Applications.

DNA nanomaterials have been widely employed for various biomedical applications. With rapid development of chemical modification of nucleic acid, serials of stimuli-responsive elements are included in the multifunctional DNA nanomaterials. In this review, we summarize the recent advances in light responsive DNA nanomaterials based on photocleavage/photodecage, photoisomerization, and photocrosslinking for efficient bioimaging (including imaging of small molecule, microRNA, and protein) and drug delivery (including delivery of small molecule, nucleic acid, and gene editing system). We also discuss the remaining challenges and future perspectives of the light responsive DNA nanomaterials in biomedical applications.

Abstract 4091: A novel cancer vaccine based on hyaluronic acid nanogel combined with adoptive T cell therapy induces complete regression of established tumors and long-lasting memory CD8+ T cells

Abstract Background: We have developed nanosized hydrogel particles (nanogels) to create new nanomaterials for biomedical applications. In particular, Hyaluronic Acid, partially hydrophobized by chemical modification with cholesteryl groups, has a distinguished characteristic to form physically cross-linked NanoGel particles. HANG efficiently forms a stable complex with an antigenic polypeptide (HANG-Vaccine) through hydrophobic interactions. In this study, we investigated the efficacy of HANG-V against tumors resistant to immune checkpoint inhibitors (ICIs) and adoptive TCR-T therapy. Methods: C57BL/6-derived B16F10 melanoma and BALB/c-derived CMS5a sarcoma are both known to be resistant to ICIs and adoptive TCR-T therapy. The efficacy of HANG-V was tested by using each tumor-bearing mice treatment model. HANG-V was prepared by mixing gp100 or CMS5a neoantigen (Ag) with HANG, respectively. Results: HANG-V was subcutaneously injected into B16F10-bearing C57BL/6 on days 7, 11, and 15, and CD8+ T cells from Pmel-1 mice were intravenously administered on days 8 and 12. Surprisingly, complete regression of established B16F10 tumors with more than 100 mm2 were observed. Vaccinated mice survived with changing hair color of mice into white, while non-vaccinated mice were all dead by day 25. Moreover, gp100-specific CTLs was observed abundantly in systemic including tumor site. Even two months after the treatment, transferred T cells with memory phenotype were persistently detected in peripheral bloods. Furthermore, booster vaccination elicited robust expansion of these memory T cells persisting for more than one year. In similar experimental settings, we treated CMS5a tumor-bearing mice by HANG-V combined with adoptive transfer of CD8+ T cells from DUC18 mice, whose T cells are specific for mutated ERK2 neoAg. All mice survived as well with complete reduction of established CMS5a tumors, rejected a rechallenge with CMS5a and induced an Ag-specific CTL responses on more than 2 years. Notably, by using neoantigen-knockout CMS5a, we obtained results suggesting that HANG-V with TCR-T therapy potently induced the so-called “antigen spreading”. Furthermore, induction of Ag-specific CTLs was associated with CD44 hyaluronic acid receptor which expressed in APCs crucial for cross-presentation to CD8+ T cells. Conclusions: HANG-V strongly enhanced the efficacy of adoptive TCR-T cell therapy against ICI refractory tumors leading to total tumor suppression. Furthermore, HANG-V induced potent and persistent Ag-specific CTLs systemically through interaction with CD44 hyaluronic receptor, allowing long-term protection of tumor recurrence with memory CD8+ T cells. Our studies may propose crucial insights for clinical application of HANG vaccine with adoptive T cell therapy in patient with ICI-resistant tumors with poor prognosis. Citation Format: Fumiyasu Momose, Takashi Nakai, Kohei Yabuuchi, Makiko Yamane, Tae Hayashi, Linan Wang, Yoshiyuki Nakagawa, Shogo Aso, Toru Katsumata, Tsuyoshi Shimoboji, Yoshihiro Miyahara. A novel cancer vaccine based on hyaluronic acid nanogel combined with adoptive T cell therapy induces complete regression of established tumors and long-lasting memory CD8+ T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4091.

Hybrid Organic Polymer/Inorganic Nano-materials for Biomedical Applications: Where we are and Where to go?

Abstract: Hybrid functional materials, composed of inorganic and organic components, are considered versatile platforms whose applications in electronics, optics, mechanics, energy storage, informatics, catalysis, sensors, and medicine field have represented a breakthrough for human well-being. Among hybrid materials, micro/nanostructured hybrid colloidal systems have been widely investigated due to the dramatic enhancement of activity provided by the large surface area exposed at the interfaces with respect to the bulk counterpart. Recently, a growing interest has been in the exploration of novel environmental-friendly and versatile procedures that allow the formulation of hybrid nanostructures through safety procedures and mild experimental conditions. This review aims to provide an introduction to hybrid organic-inorganic materials for biomedical applications in particular nanostructured ones, describing the commonly exploited materials for their fabrication and techniques, advantages, and drawbacks.

Downsizing and soft X-ray tomography for cellular uptake of interpenetrated metal-organic frameworks.

Metal-organic frameworks (MOFs) are porous materials with potential in biomedical applications such as sensing, drug delivery, and radiosensitization. However, how to tune the properties of the MOFs for such applications remains challenging. Herein, we synthesized two MOFs, Zr-PEB and Hf-PEB. Zr-PEB can be classified as porous interpenetrated zirconium frameworks (PIZOFs) and Hf-PEB is its analogue. We controlled their sizes while maintaining their crystal structure by employing a coordination modulation strategy. They were designed to serve as sensitizer for X-ray therapy and as potential drug carriers. Comprehensive characterizations of the MOFs' properties have been conducted, and the in vitro biological impacts have been studied. Since viability assay showed that Hf-PEB was more biocompatible compared to Zr-PEB, the cellular uptake of Hf-PEB by cells was evaluated using both fluorescence microscopy and soft X-ray tomography (SXT), and the three-dimensional structure of Hf-PEB in cells was observed. The results revealed the potential of Zr-PEB and Hf-PEB as nanomaterials for biomedical applications and demonstrated that SXT is an effective tool to assist the development of such materials.

Carbon nanomaterials for biomedical applications: A comprehensive review

Carbon-based nanomaterials have emerged as promising candidates for a wide range of biomedical applications due to their unique physicochemical properties and biocompatibility. This comprehensive review aims to provide an overview of the recent advancements and potential applications of carbon-based nanomaterials in the field of biomedicine. The review begins by discussing the different types of carbon-based nanomaterials, including carbon nanotubes, graphene, and fullerenes, highlighting their distinct structures and properties. It then explores the synthesis and functionalization strategies employed to tailor their physicochemical properties, facilitating their integration into various biomedical platforms. Furthermore, the review delves into the applications of carbon-based nanomaterials in biomedicine, focusing on three major areas: diagnostics, therapeutics, and tissue engineering. In diagnostics, carbon-based nanomaterials have demonstrated their utility as biosensors, imaging agents, and platforms for disease detection and monitoring. In therapeutics, they have been utilized for drug delivery, gene therapy, and photothermal therapy, among others. Additionally, carbon-based nanomaterials have shown great potential in tissue engineering, where they have been employed as scaffolds, biosensors, and substrates for cell growth and differentiation. The review also highlights the challenges and considerations associated with the use of carbon-based nanomaterials in biomedical applications, including toxicity concerns, biocompatibility, and regulatory considerations. Moreover, it discusses the current trends and future prospects in this rapidly evolving field, such as the development of multifunctional nanomaterials, combination therapies, and personalized medicine.

PCL/Fe3O4 magnetic electrospun yarn composites as a novel nanomaterial for biomedical applications

Magnetic composite structures were fabricated by embedding iron oxide nanoparticles (Fe3O4) into polycaprolactone (PCL) nanofibers through an electrospinning process. The PCL nanofibers incorporating 0.5 and 1 wt. % Fe3O4 were electrospun with various yarn and membrane architectures. SEM images of the fabricated fibers revealed diameter increment by raising the Fe3O4 proportion. Additionally, elongation at break, in tandem with the ultimate strength of the electrospun PCL yarn was improved by 63 and 67% through embedding 0.5 and 1 wt. % Fe3O4, respectively. The saturation magnetization results depended on the number of magnetic nanoparticles loaded in the electrospun fibers, as well as the architectural design of the electrospun fibers. The magnetic response of the fibrous yarns was enhanced by increasing the Fe3O4 mass fraction from 0.5 to 1 wt. %. The highest saturation magnetization of 5.38 emu/g was obtained for the electrospun yarn containing 1 wt. % Fe3O4, corroborating 13.6 times greater features than that of the fibrous membrane with a similar chemical composition. The obtained results implied that the as-spun fibrous yarn could be a great candidate as a surgical suture with the release capability of bioactive agents under a magnetic field.

Nanomaterials as targeted delivery system of therapeutics for inhibition of cancer

Cancer, a disease with complex pathological process, is the principal cause of mortality and morbidity throughout the world. Conventional chemotherapy faces drawbacks regarding its low bioavaiability, insolubility, high dose requirements, low therapeutic indices, cytotoxicity, multiple drug resistance-development, biological barriers related obstruction, and non-specific targeting. Cancer drug resistance includes over-expression of drug efflux transporters, hypoxic environment, and defective apoptotic pathways. To overcome these discrepancies, a lot of nanomaterials (NMs), as emerging delivery system, have attracted attention for carrying and delivering therapeutics to the desired sites of interest. For improving the targeting potential of the anticancer cargos, NMs are optimized for their sizes, shapes, and surfaces for enhancing their circulation time and targeting efficiency. The NMs through encapsulation or conjugation of cargos with ligands may target them to the cancer site/s with enhanced therapeutic efficacy in a controlled release manner. Generally, NMs, as cancer therapy, are utilized to target cancer cells, tumor microenvironment, and immune system mainly through enhanced permeability and retention (EPR) effect¸­ stimuli-responsive targeting or modifying their surfaces with targeting ligands such as transferin, integrins, sugar, folic acid and antibodies for the enhancement of tissue targeting recognition and their internalization. This review demonstrates mainly the biomedical applications of NMs as delivery vehicles or systems functionalized with ligands and therapeutic agents to target cancer cells / tissues passively, actively or physically with higher inhibitory therapeutic efficacies against cancer.
 Keywords: Cancer; Conventional chemotherapy; Nanomaterials; Biomedical applications; Therapeutic targeting; Inhibitory therapeutic efficacies

Porous Noble Metal‐Based Nanomaterials in Biomedical Applications

Noble metal‐based nanomaterials have attracted tremendous attention in biomedical applications due to their unique electrical, optical, and chemical properties, playing crucial roles in the ultrasensitive detection of biomarkers, bioimaging, cancer therapy, etc. Especially, porous noble metal‐based nanomaterials show superior performance due to the large specific area and multiple active sites. Platforms constructed from porous noble metal‐based nanomaterials are emerging as highly promising tools for various biomedical applications. Herein, the properties and synthesis strategies of porous noble metal‐based nanomaterials are briefly introduced. Then the recent progress of porous noble metal‐based nanomaterials in the biomedical field is highlighted, focusing primarily on their applications in optics, electrochemistry, and mass spectrometry. Finally, the challenges related to fabrication and biocompatibility for their applications while also providing an outlook on their widespread use in clinical situations are discussed. This review aims to provide further insights into the design of porous noble metal‐based nanomaterials and expand their applications in the biomedical field.

Microwave-assisted phytogenic Ag/Ag2O/ZnO nanocomposite as a replacement of Ag/Ag2O and ZnO nanoparticles: A comparative antioxidant study

A biogenic approach, particularly plant-mediated synthesis, is currently regarded as the sustainable approach for synthesizing nanomaterials (NMs). The present investigation concentrates on the green fabrication of Ag/Ag2O nanoparticles (NPs), ZnO NPs, and Ag/Ag2O/ZnO nanocomposites (NCs) via microwave irradiation using Murusi peel (MP) and Kew peel (KP) aqueous extracts and comparatively determine their antioxidant potentials. The synthesis parameters of Ag/Ag2O NPs, ZnO NPs, and Ag/Ag2O/ZnO NCs were optimized and characterized using different analytical techniques. Surface plasmon resonance peaks appeared at 448–450 nm, 350–370 nm, and 400–500 nm for Ag/Ag2O NPs, ZnO NPs, and Ag/Ag2O/ZnO NCs, respectively. The scanning electron microscopic images of both peel-mediated Ag/Ag2O NPs depicted quasi-spherical shapes aggregating on the flake-shaped ZnO surface, leading to the Ag/Ag2O/ZnO NCs formation. Transition electron microscopic analysis revealed the average particle sizes of MP and KP-mediated Ag/Ag2O NPs, ZnO NPs, and Ag/Ag2O/ZnO NCs as 13.58±1.32 nm, and 36.79±1.24 nm, 13.00±1.26 nm, and 10.28±1.25 nm, 28.37±1.39 nm, and 11.21±1.06 nm, respectively. X-ray diffraction analysis confirmed the synthesis of pure crystalline structures with a hexagonal wurtzite structure for ZnO and a face-centered structure for Ag and Ag2O during the formation of Ag/Ag2O/ZnO NCs. According to the research findings, MP and KP-mediated Ag/Ag2O/ZnO NCs displayed an enhanced free radical scavenging effect for DPPH (2,2-diphenyl-1-picrylhydrazyl) assay with IC50 values of 54.13±0.53 ppm and 51.41±1.27 ppm, respectively. At higher concentrations, the NCs exhibited a greater radical scavenging potential for ABTS (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assay, with the IC50 values for MP and KP-mediated as 72.28±0.83 ppm and 65.78±1.29 ppm, respectively. Similarly, for the FRAP (Ferric reducing antioxidant power) assay, MP and KP-mediated Ag/Ag2O/ZnO NCs demonstrated a higher antioxidant potential, expressed in terms of ascorbic acid equivalents (AE), which were 46±0.7 (AE) mg/1 g and 50±1.1 (AE) mg/1 g, respectively. To the best of our knowledge, this study remains the first comparative analysis of synergistically enhanced antioxidant potential of the agro-waste mediated Ag/Ag2O/ZnO NCs with their respective NPs counterparts, Ag/Ag2O NPs and ZnO NPs. These research findings pave the path for sustainably utilizing these NMs in biomedical applications.

“Challenges and toxicity assessment of inorganic nanomaterials in biomedical applications: Current status and future roadmaps”

“Challenges and toxicity assessment of inorganic nanomaterials in biomedical applications: Current status and future roadmaps”

The Use of Crystalline Carbon-Based Nanomaterials (CBNs) in Various Biomedical Applications

This review study aims to present, in a condensed manner, the significance of the use of crystalline carbon-based nanomaterials in biomedical applications. Crystalline carbon-based nanomaterials, encompassing graphene, graphene oxide, reduced graphene oxide, carbon nanotubes, and graphene quantum dots, have emerged as promising materials for the development of medical devices in various biomedical applications. These materials possess inorganic semiconducting attributes combined with organic π-π stacking features, allowing them to efficiently interact with biomolecules and present enhanced light responses. By harnessing these unique properties, carbon-based nanomaterials offer promising opportunities for future advancements in biomedicine. Recent studies have focused on the development of these nanomaterials for targeted drug delivery, cancer treatment, and biosensors. The conjugation and modification of carbon-based nanomaterials have led to significant advancements in a plethora of therapies and have addressed limitations in preclinical biomedical applications. Furthermore, the wide-ranging therapeutic advantages of carbon nanotubes have been thoroughly examined in the context of biomedical applications.

EMI Shielding and Conductive Textiles Functionalized with (Ti,Cu) Nanomaterials for Biomedical Applications.

This study explores the potential of integrating thin-film technology in the design of new and effective electromagnetic interference (EMI) shielding and conductive materials for textiles and wearables. This application is of particular interest to the textile industry as it can bring new functionalities to wearables and protect humans from prolonged exposure to EM radiation. Three different thin films of pure Ti, pure Cu, and Ti-doped with Cu prepared by magnetron sputtering were used to functionalize textile knits based on cotton (code 39F) and lyocell fibers (62I). The films displayed different crystalline structures, morphologies, and topographies, which depended on their chemical compositions. The shielding effectiveness (SE) of the functionalized knits against EMI was evaluated in the frequency range of 2-8 GHz. Also, the electrical response under stress was assessed since the electrical conductivity is closely related to the EMI shielding effectiveness. The results demonstrate the feasibility of using a thin conductive layer based on Cu or Ti-Cu to improve the shield textiles with great adhesion and low thickness, providing an interesting path to improve shielding efficiency for EMI without modifying the flexibility of the textiles.

Superparamagnetic and antimicrobial biosynthesis of Ce/NiO nanomaterials for biomedical applications

Nanomaterials have been used in advanced biomedical applications due to their superparamagnetic and antimicrobial properties. The adequate superparamagnetic and antimicrobial capacity has improved the nanomaterials applicability in biomedical applications. Herein, superparamagnetic and antibacterial Ce doped NiO nanomaterials were developed by dissolving cerium(III) nitrate and nickel(II) nitrate at different concentrations (1-X, X = 0.001, 0.002 and 0.003, and 0.099, 0.098 and 0.097 M, respectively) using Azadirachta Indica extract as a nucleation agent. The oxidation states Ni(2p), Ce(3d) and O(1s) of the nanomaterials were investigated by XPS spectra. The XRD patterns determined that the Ce doped NiO nanomaterials exhibit face-centred​ cubic structures. FE-SEM illustrates the surface structure of the nanomaterials, which have non-uniform spherical particles. Photoluminescence spectra reveal multi-emission centres​ created in the nanostructure. In addition, the electrical and magnetic behaviours of the Ce-doped NiO nanomaterials were investigated to determine the dielectric polarization and magnetic properties. The nanomaterials’ superparamagnetic behaviour was studied using a vibrating sample magnetometer at ambient temperature. Additionally, nanostructures’ bacterial activity significantly inhibited Staphylococcus Aureus and Klebsiella Pneumoniae. This investigation indicates that forming a nanostructure has significant advantages in biomedical applications.

Differential electrochemical behaviour of phytofabricated and chemically synthesized silver nanoparticles towards hydrogen peroxide sensing**

AbstractSilver nanoparticles (AgNPs) are one of the most widely used nanomaterials for biomedical applications. However, the impact of its synthesis by chemical and plant‐mediated routes on its differential electrochemical behaviour has not been examined till date. Here, we report for the first time the differential study of the electrochemical behaviour of the AgNPs synthesized by different routes. First, the AgNPs were obtained by different routes (chemical and phytofabrication) and extensively characterized to compare their physical properties. Thereafter, a comparison of electron transfer kinetics between chemically synthesized (Ag−C) and phyto‐fabricated (Ag‐Phy) nanoparticles (NPs) has been studied by electrochemical techniques such as potentiodynamic cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). To further investigate the electrocatalytic properties of both types of AgNPs, we have used the peroxide moieties (H2O2), and the Ag−C NPs‐based sensor probe has been reported to have four times better sensitivity than the Ag−Phy NPs‐based sensor. The AgNPs modified sensor probes have also been tested in real‐world environments to explore the consistency of their performance in complex matrices by using clinical urine samples, where we found comparable sensitivity to the standard conditions.

Structurally Engineered Silica Shells on Gold Nanorods for Biomedical Applications

Owing to their unique optical and chemical properties, gold nanorods (AuNRs) are among the most frequently used nanomaterials for biomedical applications, including cancer therapy, imaging, and drug delivery. In particular, the longitudinal dipole plasmon wavelength of AuNRs can be verified from the visible to the near‐infrared (NIR) region, allowing AuNRs to be used as photodynamic/photothermal and imaging contrast agents. At the same time, the silica shell is important as it enhances stability and facilitates the functionalization and biocompatibility of AuNRs, offering numerous advantages in biomedical applications. In this review, silica‐coated AuNRs from a bioapplication perspective are focused. First, the importance of AuNRs for biomedical applications is explained and the purpose of silica coating on AuNRs is discussed. Then, recent studies on the development of silica‐coated AuNRs from a biomedical perspective are reviewed. Subsequently, various strategies for engineering silica coatings and their properties in the biomedical field are reviewed. This review is expected to promote further research on next‐generation silica‐coated AuNRs for biomedical applications.

Graphene-encapsulated iron nanoparticles as a non-viral vector for gene delivery into melanoma cells

The rapid progress of nanotechnology has led to use different nanomaterials for biomedical applications. Among them, graphene-encapsulated magnetic nanoparticles (GEMNS) are recognized as next generation carbon nanomaterials in translation cancer research. In this study, we utilized green fluorescence protein (GFP) expression plasmid DNA (pDNA) and GEMNS decorated with branched polyethyleneimine (PEI) to yield a novel transporter (GEMNS-PEI/pDNA) for gene delivery into melanoma cells (B16F10). The efficiency of transfection was examined using PCR and confocal microscopy. The studies show that the as-designed GEMNS-PEI construct is successfully used to transfect the melanoma cells with pDNA and it should be considered as a potent non-viral vector for introducing naked nucleic acids into eucaryotic cells.

Promotion of protein assembly by nanoparticles: From in vitro to in-cell.

Engineered nanomaterials are increasingly being studied for biomedical applications such as in diagnosis and therapeutics, due to their similarity in size to subcellular scales, and their tunable physico-chemical properties. Nanomaterials acquire a biomolecular corona upon introduction to biological media, which can influence their biological identity and subsequently, their interactions within the cell. Nanoparticle-protein interactions at the nano-bio interface also affect proteins in the corona, leading to biological transformations such as a change in protein function, unmasking new epitopes, and fibrilization. Silica nanoparticles - one of the most widely studied nanomaterials in biomedical applications - were reported to show a dose-dependent or surface ligand-dependent effect on the kinetics and morphology of protein self-assembly in systems like amyloid-β fibrils, α-synuclein and lysozyme. The interaction of silica nanoparticles with polymerizing cytoskeletal proteins, specifically tubulin proteins, has not been investigated quantitatively. BtubA and BtubB are a pair of bacterial tubulin proteins identified in Prosthecobacter strains, acquired by bacteria from eukaryotic cells via horizontal gene transfer. BtubAB dimers are known to self-assemble like eukaryotic tubulin, forming four-stranded microtubules in vitro as well as five-stranded microtubules in vivo. FRET-labeling of each of the Btub monomers with a donor (mEGFP) and acceptor (mRuby3) fluorescent protein provides a quantitative tool to measure the binding interactions of BtubAB dimers in the presence of silica nanoparticles in vitro and in cell using fluorescence spectroscopy and microscopy. We show that silica nanoparticles enhance BtubAB dimerization in vitro, whereas they appear to have little effect on bacterial tubulin self-assembly in the complex mammalian cellular environment.

Agglomerated serum albumin adsorbed protocatechuic acid coated superparamagnetic iron oxide nanoparticles as a theranostic agent

Iron oxide nanoparticles have been one of the most widely used nanomaterials in biomedical applications. However, the incomplete understanding of the toxicity mechanisms limits their use in diagnosis and treatment processes. Many parameters are associated with their toxicity such as size, surface modification, solubility, concentration and immunogenicity. Further research needs to be done to address toxicity-related concerns and to increase its effectiveness in various applications. Herein, colloidally stable nanoparticles were prepared by coating magnetic iron oxide nanoparticles (MIONPs) with protocatechuic acid (PCA) which served as a stabilizer and a linkage for a further functional layer. A new perfusion agent with magnetic imaging capability was produced by the adsorption of biocompatible passivating agent macro-aggregated albumin (MAA) on the PCA-coated MIONPs. PCA-coated MIONPs were investigated using infrared spectroscopy, thermogravimetric analysis and dynamic light scattering while adsorption of MAA was analysed by transmission electron microscopy, Fourier-transform infrared spectroscopy and x-ray diffraction methods. Magnetic measurements of samples indicated that all samples showed superparamagnetic behaviour. Cytotoxicity results revealed that the adsorption of MAA onto PCA-coated MIONPs provided an advantage by diminishing their toxicity against the L929 mouse fibroblast cell line compared to bare Fe3O4.

Quantification of monodisperse and biocompatible gold nanoparticles by single-particle ICP-MS.

Bioanalytical and biomedical applications often require nanoparticles that exhibit narrow size distributions and biocompatibility. Here, we demonstrate how different synthesis methods affect gold nanoparticle (AuNPs) monodispersity and cytotoxicity. Using single particle inductively coupled plasma mass spectrometry (SP-ICP-MS), we found that the size distribution of AuNPs synthesized with a cetyltrimethylammonium chloride (CTAC) cap was significantly improved compared to AuNPs synthesized with citrate capping agents. We determined an up to 4× decrease in the full width at half maximum (FWHM) value of the normal distributions of AuNP diameter and up to a 12% decrease in relative standard deviation (RSD). While the CTAC-capped AuNPs exhibit narrow nanoparticle size distributions, they are cytotoxic, which limits safe and effective bioanalytical and biomedical applications. We sought to impart biocompatibility to CTAC-capped AuNPs through a PEGylation-based surface ligand exchange. We developed a unique ligand exchange method driven by physical force. We demonstrated the successful PEGylation using various PEG derivatives and used these PEGylated nanoparticles to further bioconjugate nucleic acids and peptides. Using cell viability quantification, we confirmed that the monodisperse PEGylated AuNPs were biocompatible. Our monodisperse and biocompatible nanoparticles may advance safe and effective bioanalytical and biomedical applications of nanomaterials.

Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications.

Zinc oxide nanoparticles (ZnO NPs), an attractive oxide semiconductor material, are widely used in the biomedical field due to their good biosafety and economy. The proposal of stimuli-responsive materials provides a new way for the further application of single ZnO-based nanomaterials that cannot meet the ever-changing requirements. In this review, the emerging advances in exogenous stimuli (light, ultrasound, mechanical force, etc.) and endogenous stimuli (pH, enzymes, etc.) responsive systems of ZnO-based nanomaterials in biomedical applications are highlighted. First, the basic characteristics, response mechanisms and construction principles of single-stimulus-responsive ZnO-based nanomaterials, as well as their recent advances in tissue repair, medical devices and theranostics are summarized. Subsequently, the design method of multi-stimuli-responsive ZnO-based biomaterials is discussed, and the application advantages of multi-functional responsive systems are explained by analyzing typical cases of biomedical applications of multi-responsive strategies. Finally, we discuss the prospects for the design and development of stimuli-responsive ZnO-based biomaterials for biomedical applications and point out their advantages as well as the places that need to be further improved. The current review may provide a useful reference for researchers interested in constructing such abundant, inexpensive and widely applicable multi-stimuli-responsive materials.