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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Nanoscience".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 7020

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Prof. Dr. Gangho Lee

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Department of Chemistry, Kyungpook National University, Daegu 41566, Republic of Korea
Interests: nanomaterials; nanomaterial synthesis; imaging agents; nanomedicine; contrast agents; nanoparticle colloid; surface modification
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Dear Colleagues,

Nanoparticles, nanomaterials, nanorods, core–shell nanoparticles, and hybrid nanoparticles have been extensively studied for their use in various biomedical applications, including as contrast agents in magnetic resonance imaging (MRI) and X-ray computed tomography (CT), as well as in drug delivery, fluorescent imaging, biolabeling, biosensing, etc. Their properties are superior to those of conventional molecules and chelates. Many reports have detailed their synthesis, physicochemical properties, and biomedical applications, highlighting their unique and advanced properties that make them particularly useful in the diagnosis of diseases.

The aim of this Special Issue is to showcase a variety of nanoparticles and nanomaterials that can be applied in biomedicine, nanomedicine, and nanobiology, with a focus on their physicochemical properties and biomedical applications. The key topics addressed in this Issue will include the synthesis of nanoparticles and nanomaterials, the characterization of their physicochemical properties using various techniques, surface modification processes, and in vitro and in vivo biomedical applications. The surface modification of nanoparticles and nanomaterials with hydrophilic and biocompatible ligands is essential for their use in biomedical applications.

Prof. Dr. Gangho Lee
Guest Editor

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Keywords

nanoparticle
nanomaterial
biomedicine
synthesis
physicochemical properties
imaging
therapy
contrast agent
therapeutic agent

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Published Papers (9 papers)

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Research

24 pages, 9275 KB

Open AccessArticle

A Simple Ionic-Gelation Method for Chitosan Nanoparticle Synthesis and Standardized Protocols for Biological Safety Assessment: Antibacterial Activity, Phytotoxicity, and Biocompatibility

by Kanchit Rahaeng, Atcha Oraintara and Wuttipong Mahakham

Int. J. Mol. Sci. 2026, 27(8), 3673; https://doi.org/10.3390/ijms27083673 - 20 Apr 2026

Viewed by 228

Abstract

Chitosan nanoparticles (Ch NPs) are versatile nanomaterials with expanding agricultural and biomedical applications, highlighting the need for reproducible, low-cost, and scalable synthesis methods to ensure their safe and widespread use in biological systems. This study presents a simple ionic-gelation protocol using a serological pipette–needle dropwise system that minimizes reagent waste and requires no sophisticated equipment. The synthesized Ch NPs were characterized by UV–Vis spectroscopy, ESEM, TEM, EDS, DLS, XRD, and FTIR, confirming nanoscale size, strong positive surface charge, and characteristic chitosan–TPP interactions. To establish a standardized biological safety assessment framework, three representative bioassays were implemented across microbial, plant, and mammalian systems. Antibacterial testing against Xanthomonas oryzae pv. oryzae (Xoo) using a resazurin-based microdilution assay revealed a minimum inhibitory concentration (MIC) of 128 µg/mL, whereas bulk chitosan showed no inhibition up to 512 µg/mL. Phytotoxicity and seed germination assays on rice (Oryza ‘KDML105’) demonstrated no inhibitory effects on germination, with over 90% germination by day 3 and significantly enhanced seedling growth parameters (p < 0.05) at 64–128 µg/mL, indicating non-phytotoxicity. MTT assays confirmed that Ch NPs were non-toxic to both human skin cell lines (HDF and HaCaT) across 2.5–160 µg/mL, showing enhanced cell viability in HDF cells at specific concentrations and stable viability in HaCaT cells, indicating overall biocompatibility. Importantly, all bioassays were conducted under aligned concentration ranges to enable cross-system comparison and reproducibility. This integrated workflow links nanoparticle synthesis with a standardized, multi-system evaluation strategy, supporting the safe application of Ch NPs in biological systems. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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23 pages, 3209 KB

Open AccessArticle

Alverine-Loaded Lipid Bilayer–Graphene Oxide Hybrids as a Novel Nanomedicine Platform for Neural Cancer

by Alicja Przybylska, Irina Naletova, Francesco Attanasio, Katarzyna Dopierała, Agnieszka Kołodziejczak-Radzimska and Cristina Satriano

Int. J. Mol. Sci. 2026, 27(7), 3273; https://doi.org/10.3390/ijms27073273 - 4 Apr 2026

Viewed by 426

Abstract

Graphene oxide (GO)–lipid hybrid nanostructures represent a promising class of multifunctional platforms for drug delivery and fluorescence-guided cellular imaging. In this study, we developed a graphene oxide-supported lipid bilayer system composed of rhodamine-labeled phosphatidylcholine (POPC-Rhod) for the delivery of the repurposed antispasmodic drug alverine citrate (ALV) to neuroblastoma cells. The hybrid nanostructures were assembled using two drug-loading strategies and characterized by UV–Vis spectroscopy, fluorescence analysis, dynamic light scattering, and atomic force microscopy to evaluate molecular interactions, vesicle size distribution, and nanomechanical properties. In vitro studies were performed using human neuroblastoma SH-SY5Y cells and their retinoic acid-differentiated neuronal-like counterparts. Confocal microscopy confirmed efficient cellular uptake of the fluorescent lipid–graphene hybrids, while viability and mitochondrial reactive oxygen species assays revealed differentiation-dependent cellular responses. ALV-loaded hybrids induced cytotoxic effects in proliferating neuroblastoma cells, whereas differentiated neuron-like cells exhibited greater tolerance and, at moderate concentrations, preserved viability despite increased oxidative stress. These findings demonstrate that graphene oxide–lipid hybrids can act as fluorescence-traceable drug delivery platforms and highlight the potential of alverine as a candidate for repurposing in neural cancer models. The system presented here provides a proof-of-concept framework for the development of multifunctional nanocarriers integrating therapeutic delivery with imaging capabilities. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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25 pages, 5878 KB

Open AccessArticle

Synthesis and Characterization of Mg-Doped CuO Nanoparticles and Their Enhanced Anticancer Efficacy Against HepG2 Liver Cancer Cells

by Chanachon Supha, Ramzan Ahmed, Vichugorn Wattayagorn, Sirikanjana Thongmee and Pramote Chumnanpuen

Int. J. Mol. Sci. 2026, 27(4), 1647; https://doi.org/10.3390/ijms27041647 - 8 Feb 2026

Cited by 1 | Viewed by 531

Abstract

The rising global incidence of hepatocellular carcinoma demands innovative therapeutic strategies. This study explores the enhanced anticancer potential of magnesium-doped copper oxide (Mg-doped CuO) nanoparticles, which were synthesized to improve upon the properties of undoped CuO nanoparticles. Mg-doped CuO nanoparticles with doping concentrations ranging from 1% to 5% were prepared using the co-precipitation method and thoroughly characterized by SEM, EDS, and FTIR. Their biological activity was evaluated against HepG2 liver cancer cells and normal human fibroblast cells. The MTT assay demonstrated a significant, concentration-dependent increase in cytotoxicity for Mg-doped CuO nanoparticles compared to undoped CuO, with the 3% Mg-doped CuO formulation showing the greatest potency (IC₅₀ = 21.99 µg/mL at 48 h). Cell cycle analysis revealed that treatment with Mg-doped CuO nanoparticles, particularly at 3% and 5% doping concentrations, induced a substantial G2/M phase arrest, indicating a mechanism of action involving the disruption of cell division. Furthermore, all Mg-doped CuO nanoparticles exhibited markedly higher IC₅₀ values in normal fibroblasts, confirming a favorable selective toxicity towards cancer cells. Apoptosis was identified as a key cell death pathway through acridine orange/propidium iodide staining. These results conclusively show that magnesium doping significantly augments the selective anticancer efficacy of CuO nanoparticles via cell cycle arrest and apoptosis induction, presenting a highly promising nanomaterial targeted liver cancer therapy. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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19 pages, 5301 KB

Open AccessArticle

Water Proton Spin Relaxivities and Absolute Fluorescent Quantum Yields of Triply and Quadruply Mixed Lanthanide Oxide Nanoparticles

by Abdullah Khamis Ali Al Saidi, Tirusew Tegafaw, Dejun Zhao, Ying Liu, Endale Mulugeta, Xiaoran Chen, Ziyi Lin, Hansol Lee, Ahrum Baek, Jihyun Kim, Yongmin Chang and Gang Ho Lee

Int. J. Mol. Sci. 2026, 27(2), 959; https://doi.org/10.3390/ijms27020959 - 18 Jan 2026

Viewed by 489

Abstract

Multicomponent mixed lanthanide oxide (MMLO) nanoparticles possess considerable potential as multimodal imaging agents because they integrate diverse excellent optical and magnetic properties within a single nanoparticle. Herein, we present triply and quadruply mixed lanthanide oxide nanoparticles, namely, gadolinium (Gd)/dysprosium (Dy)/europium (Eu) oxide (GDEO), Gd/Dy/terbium (Tb) oxide (GDTO), and Gd/Dy/Eu/Tb oxide (GDETO) nanoparticles. Gd³⁺ can strongly induce positive (T₁) contrast in magnetic resonance imaging (MRI), Dy³⁺ and Tb³⁺ can generate negative (T₂) contrast in MRI, and Eu³⁺ and Tb³⁺ emit visible photons that are applicable to fluorescence imaging (FI). All the nanoparticles were grafted with hydrophilic, biocompatible polyacrylic acid (PAA) to enhance colloidal stability and biocompatibility and further grafted with small amounts of an organic photosensitizer, 2,6-pyridinedicarboxylic acid (PDA), to obtain a high absolute fluorescent quantum yield (QY) with an extended fluorescent lifetime (τ). All PAA-MMLO and PAA/PDA-MMLO nanoparticles exhibited nearly monodispersed particle-size distributions with average particle diameters of ~2 nm and displayed considerably higher longitudinal (r₁) and transverse (r₂) water proton spin relaxivities than commercial molecular MRI contrast agents. The PAA/PDA-GDEO, PAA/PDA-GDTO, and PAA/PDA-GDETO nanoparticles exhibited high absolute QYs of 45, 29, and 61%, respectively, and long τ values of 1–2 ms, making them suitable for time-delayed noise-free fluorescence signal detection. These findings confirm the high potential of PAA-MMLO nanoparticles as T₁ and/or T₂ MRI contrast agents and PAA/PDA-MMLO nanoparticles as both T₁ and/or T₂ MRI and FI agents. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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16 pages, 5467 KB

Open AccessArticle

Butyrylcholinesterase-Loaded Liposomes and Polymersomes: Catalytic Parameters for Three Types of Substrates

by Zukhra Shaihutdinova, Svetlana Batasheva, Patrick Masson and Tatiana Pashirova

Int. J. Mol. Sci. 2026, 27(1), 190; https://doi.org/10.3390/ijms27010190 - 24 Dec 2025

Viewed by 612

Abstract

The nano-technological approach and supramolecular chemistry principles relation to the encapsulation of enzymes pave the way for creating next-generation nano-system-functionalized nano-compartments. The most promising approach for prophylaxis and the treatment of organophosphate (OP) poisoning is the use of stable, bioavailable nano-compartments containing OP-scavenging enzymes. Such enzymes, like butyrylcholinesterase (BChE), wild type and mutants, could also be used for the detoxification of other poisonous esters. There are two types of IRD-labeled human BChE-containing nano-scavengers: PEGylated liposomes and polyethyleneglycol–polypropylenesulfide polymersomes, which were developed with diameter close to 100 nm. BChE-polymersomes have higher encapsulation efficiency (95%) and slower release rate of enzymes (more than 7 days) compared to BChE-liposomes. The catalytic properties of encapsulated enzymes were analyzed for nano-compartment formulations, lipophilicity, the structure of block copolymers, and for different ester substrate polarity: positively charged butyrylthiocholine iodide, neutral phenyl acetate, and negatively charged aspirin. The highest k_cat (more than three times) compared to non-encapsulated BChE was for polymersomes based on diblock PEG-PPS polymersomes towards the neutral phenyl acetate substrate. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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19 pages, 3290 KB

Open AccessArticle

Amphiphilic Poly(N-vinylpyrrolidone) Biocomposites with Bortezomib and DR5-Selective TRAIL Variants: A Promising Approach to Pancreatic Cancer Treatment

by Ekaterina Kukovyakina, Alina A. Isakova, Dmitry Bagrov, Marine Gasparian, Andrey Kuskov and Anne Yagolovich

Int. J. Mol. Sci. 2025, 26(23), 11620; https://doi.org/10.3390/ijms262311620 - 30 Nov 2025

Cited by 1 | Viewed by 738

Abstract

A promising strategy for pancreatic cancer therapy involves developing nanocarriers capable of simultaneously delivering various antitumor substances with diverse physicochemical properties, often resulting in synergistic effects. In the present work, novel biocomposites were developed using amphiphilic N-vinylpyrrolidone polymer incorporating bortezomib (BTZ) and modified with either the DR5-selective TRAIL cytokine (DR5-B) or its fusion with the iRGD effector peptide (DR5-B-iRGD), resulting in AmphPVP-BTZ-DR5-B and AmphPVP-BTZ-DR5-B-iRGD formulations. The release of BTZ was most extensive at acidic pH 5.6, mimicking endolysosomal compartments, while at near-neutral pH 7.4 and alkaline pH 8.2 the release was slower and less complete, indicating a smart pH-responsive behavior suitable for triggered release in the tumor microenvironment. Both AmphPVP-BTZ-DR5-B and AmphPVP-BTZ-DR5-B-iRGD significantly inhibited the growth of pancreatic adenocarcinoma cell lines PANC-1, BxPC-3, and MIA PaCa-2 and induced more rapid internalization of the DR5 receptor in MIA PaCa-2 cells than unmodified particles and free DR5-B or DR5-B-iRGD. Importantly, AmphPVP-BTZ-DR5-B-iRGD exhibited a more pronounced DR5 internalization rate and cytotoxic effect than AmphPVP-BTZ-DR5-B owing to the presence of fusion protein with internalizing iRGD peptide. Both biocomposites induced cell death via the apoptotic pathway while exhibiting minimal cytotoxic effects on healthy cells. Therefore, biocomposites incorporating BTZ and functionalized with DR5-selective TRAIL variants DR5-B or DR5-B-iRGD represent a promising avenue for future studies in pancreatic cancer animal models. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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21 pages, 7261 KB

Open AccessArticle

Albumin-Phthalocyanine Nanoconjugates as Platforms for Enhanced Photodynamic Cancer Therapy

by Valentina I. Gorbacheva, Anastasiia O. Syrocheva and Ekaterina P. Kolesova

Int. J. Mol. Sci. 2025, 26(23), 11559; https://doi.org/10.3390/ijms262311559 - 28 Nov 2025

Cited by 2 | Viewed by 650

Abstract

This study investigates the enhancement of photodynamic therapy (PDT) efficacy through the encapsulation of platinum phthalocyanine (Pc) in albumin nanoparticles (ANP). Encapsulation of Pc in ANP) significantly enhances its biological effects in photodynamic therapy by increasing cellular uptake through receptor-mediated endocytosis and promoting lysosomal accumulation. This leads to marked lysosomal stress and regulated necrotic cell death pathway, while free Pc causes moderate oxidative stress with reversible apoptosis and autophagy. The enhanced phototoxicity of encapsulated Pc was evident across multiple cancer cell lines, especially aggressive phenotypes, whereas resistant lines showed lower sensitivity likely due to efficient ROS scavenging. Despite improved initial uptake, rapid lysosomal release and extracellular extrusion of Pc limit long-term intracellular retention. Morphological and gene expression analyses confirmed distinct cell death mechanisms between free and encapsulated Pc, underscoring the critical role of nanocarrier-mediated delivery in modulating oxidative stress and cellular response. These findings highlight the importance of nanoparticle design in optimizing PDT efficacy by effectively triggering necrotic cell death pathway. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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10 pages, 803 KB

Open AccessArticle

Emulsified Homo (Ciprofloxacin) Polymer Nanoparticles for Antibacterial Applications

by Faeez Mahzamani and Edward Turos

Int. J. Mol. Sci. 2025, 26(20), 10034; https://doi.org/10.3390/ijms262010034 - 15 Oct 2025

Viewed by 576

Abstract

We report for the first time a method for forming polyacrylate nanoparticles using N-acryloylciprofloxacin as a sole monomer for emulsion polymerization. The procedure involves a free radical-induced emulsion polymerization of N-acryloylciprofloxacin monomer to produce a stable aqueous emulsion comprising uniformly sized polyacrylate nanoparticles. Dynamic light scattering analysis of the emulsions showed a single population of nanoparticles having an average diameter of 970 nm and average surface charge of −63 mV, indicative of the high stability of the emulsion and significantly enhance lipophilicity of the polymeric matrix of the nanoparticle. Antibacterial testing of the emulsions against the Gram-positive microbe Staphylococcus aureus and the Gram-negative Escherichia coli found in vitro activities identical to those of the reference clinical agent, ciprofloxacin. Assays against human colorectal carcinoma cells and human embryonic kidney cells showed essentially no cytotoxicity. This is the first study on the synthesis of aqueous nanoparticle emulsions assembled solely from a single monomer derived from the antibiotic agent. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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17 pages, 2281 KB

Open AccessArticle

Natural Polysaccharide-Based Nanoparticles Enhance Intracellular Delivery and Cytotoxicity of Antrodia camphorata in Breast Cancer Cells

by Yu-Chen Tsai, Hiroki Miyajima, Ming-Yang Chou and Satoshi Fujita

Int. J. Mol. Sci. 2025, 26(17), 8420; https://doi.org/10.3390/ijms26178420 - 29 Aug 2025

Cited by 3 | Viewed by 2233

Abstract

Antrodia camphorata (AC), a medicinal fungus native to Taiwan, contains bioactive compounds such as triterpenoids with anticancer properties. However, their high lipophilicity results in poor aqueous solubility and limited bioavailability, restricting their therapeutic application. To address this issue, a nanoparticle-based delivery system was developed using chitosan, alginate, and hyaluronic acid to encapsulate AC extracts. AC-loaded nanoparticles (AC-NPs) with a particle size less than 100 nm improved drug solubility and facilitated intracellular accumulation. Assessment of cytotoxicity revealed that AC-NPs significantly and more effectively suppressed the growth of breast cancer cells than free AC extracts. After 72 h, IC₅₀ values for MDA-MB-231 (triple-negative) and MCF-7 (estrogen receptor-positive) were 46.9 and 75.6 μg/mL, respectively, with greater sensitivity observed in MDA-MB-231 cells. AC-NPs exhibited minimal toxicity toward normal mammary epithelial cells (NMuMG), indicating good biocompatibility. Fluorescently labeled AC-NPs showed rapid, time-dependent uptake in both cancer cell lines. Particularly, MDA-MB-231 cells exhibited rapid internalization, whereas MCF-7 cells likely benefited from hyaluronic acid-mediated targeting of CD44 receptors. In conclusion, AC-NPs enhanced the solubility, cellular uptake, and anticancer efficacy of AC while maintaining biocompatibility, thereby suggesting their robust potential as nanocarrier platforms for breast cancer therapy. Full article

(This article belongs to the Special Issue Physicochemical Properties and Applications of Nanomaterials in Biology and Medicine)

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