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Pharmaceutics
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Advanced Nanomaterials for Drug Delivery, 2nd Edition
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Advanced Nanomaterials for Drug Delivery, 2nd Edition

A Special Issue of Pharmaceutics (ISSN 1999-4923) belonging to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 10739

Editors

Dr. Roxana Cristina Popescu

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Guest Editor
Department of Life and Environmental Physics, Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, 077125 Magurele, Romania
Interests: thin films; biomaterials; materials chemistry; cancer research; biomedical engineering; microscopy; tumors; cells
Special Issues, Collections and Topics in MDPI journals
Dr. Diana Savu

E-Mail Website
Guest Editor
Department of Life and Environmental Physics, Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, 077125 Magurele, Romania
Interests: radiobiology; neuro-oncology; cellular and molecular biology; DNA damage signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to a Special Issue of Pharmaceutics entitled “Advanced Nanomaterials for Drug Delivery, 2nd Edition”. It is known that nanoparticle-based systems for therapeutic applications have the ability to pass through biological barriers and target the affected tissues. In the case of drug delivery systems based on nanoparticles, they can enter, and accumulate in, the targeted cells and reach the drug therapeutic target while reducing its systemic toxicity. Moreover, the release of the drug can be controlled and triggered by environmental factors such as pH, light, or enzymes.

This Special Issue will cover recent advancements in nanoparticle design and synthesis for drug delivery applications, characterization, and evaluation, as well as in vitro, in vivo, clinical, or in silico testing. Applications in cancer therapy, antimicrobial or antiviral agents, wound healing, or tissue regeneration can be addressed.

We look forward to receiving your contributions.

Dr. Roxana Cristina Popescu
Dr. Diana Savu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nanomaterials
  • drug delivery systems
  • cancer therapy
  • antimicrobial applications
  • antiviral applications

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Published Papers (7 papers)

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Research

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17 pages, 8776 KB  
Article
Evaluation of Histidine–Octamer-Modified Hyaluronic Acid as a Cytosolic Drug Delivery Material via CD44-Mediated Cellular Uptake and Endosomal Escape
by Tomona Yukimura, Hirono Ito, Takahiro Suzuki, Toshinobu Seki and Tomohiro Seki
Pharmaceutics 2026, 18(9), 1137; https://doi.org/10.3390/pharmaceutics18091137 - 10 Sep 2026
Viewed by 231
Abstract
Background: Although intracellular delivery via endocytosis is a promising strategy for drugs acting in the cytosol or nucleus, many macromolecular therapeutics remain trapped within endosomal/lysosomal compartments, limiting efficient cytosolic delivery. In this study, we designed a novel functional hyaluronic acid (HA)-based polymer, HA–octahistidine [...] Read more.
Background: Although intracellular delivery via endocytosis is a promising strategy for drugs acting in the cytosol or nucleus, many macromolecular therapeutics remain trapped within endosomal/lysosomal compartments, limiting efficient cytosolic delivery. In this study, we designed a novel functional hyaluronic acid (HA)-based polymer, HA–octahistidine (His8), by conjugating His8 to CD44-targeting HA, and evaluated its physicochemical properties, cellular uptake, and endosomal escape capability. Methods: HA–His8 was synthesized via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS)-mediated coupling and characterized using 1H NMR spectroscopy. Particle size and zeta potential were measured via dynamic light scattering, and buffering capacity was evaluated using acid–base titration. Cellular uptake and intracellular localization were investigated in CD44-high MDA-MB-231 and CD44-low MCF-7 cells via confocal laser scanning microscopy. Cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Successful conjugation of His8 was confirmed with a degree of substitution of 4.66 mol% relative to HA carboxyl groups. HA–His8 exhibited a nanoscale hydrodynamic diameter under physiological conditions, which increased under acidic conditions together with changes in zeta potential. HA–His8 exhibited higher buffering capacity than free His8 and was preferentially internalized by CD44-high MDA-MB-231 cells compared with MCF-7 cells. Compared with unmodified HA, HA–His8 exhibited lower colocalization with LysoTracker that decreased over time, indicating reduced retention within acidic vesicles. HA–His8 also exhibited low cytotoxicity over the tested concentration range. Conclusions: His8 modification alters HA intracellular localization while preserving CD44 targeting, thereby facilitating endosomal escape. These findings highlight HA–His8 as a potential platform for the cytosolic delivery of macromolecular therapeutics, including proteins, peptides, and nucleic acids. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery, 2nd Edition)
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19 pages, 3267 KB  
Article
NIR-Responsive Gold-Decorated Phase-Change Nanodroplets for Photothermal-Triggered Pulsatile Doxorubicin Release and Enhanced Combined Photothermal-Chemotherapy in Triple-Negative Breast Cancer
by Luyao Ma, Fulai Chen, Qinghao Xu, Jianwei Yu, Yang Liu and Lei Duan
Pharmaceutics 2026, 18(7), 816; https://doi.org/10.3390/pharmaceutics18070816 - 30 Jun 2026
Cited by 1 | Viewed by 754
Abstract
Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling [...] Read more.
Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform. Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis. Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal–chemotherapeutic effect in 4T1 TNBC cells. Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery, 2nd Edition)
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29 pages, 1603 KB  
Article
Gadolinium-Doped Iron Oxide Nanoparticles Enhance Radiosensitivity in Melanoma Models Associated with Metabolic Dysfunction
by Roxana Cristina Popescu, Cosmin Catalin Mustaciosu, Adrian-Ionut Nicoara, Paul Emil Mereuta, Verena Kopatz, Roxana Trusca, Stela Patrascu, Elif Menlivuap, Cosmin-Florin Sovan, Diana Iulia Savu and Sorin Ion Jinga
Pharmaceutics 2026, 18(5), 525; https://doi.org/10.3390/pharmaceutics18050525 - 26 Apr 2026
Viewed by 1058
Abstract
Background. Nanoparticle-mediated radiotherapy is a promising approach to enhance tumor radiosensitivity while reducing damage to healthy tissues. Particularly, melanoma is a highly aggressive malignancy with an increasing global incidence and limited therapeutic options in advanced stages, due to its intrinsic radioresistance and narrow [...] Read more.
Background. Nanoparticle-mediated radiotherapy is a promising approach to enhance tumor radiosensitivity while reducing damage to healthy tissues. Particularly, melanoma is a highly aggressive malignancy with an increasing global incidence and limited therapeutic options in advanced stages, due to its intrinsic radioresistance and narrow therapeutic window in metastatic settings. In this study, we developed a systematic library of gadolinium-doped iron oxide nanoparticles (Fe-Gd NPs) with controlled compositions (0–75% Gd) to investigate the functional and compositional determinants of radiosensitization in melanoma. Methods. The physicochemical properties of the Fe-Gd NPs, including the morphology, crystallinity, and composition, were thoroughly characterized and correlated with biological responses. The biological evaluation was performed using both 2D and tissue-relevant 3D melanoma models, integrating metabolic viability assays (MTT/MTS), mitochondrial function (ATP quantification, MitoTracker analysis), and clonogenic survival following low-energy X-Ray irradiation (150 kV, 4 Gy). In vivo systemic tolerance and response in non-tumor tissues were investigated in BALB/C mice. Results. Our results showed that radiosensitization did not increase linearly with the Gd content, with the 25% Fe-Gd NPs being identified as a therapeutic window and having the most pronounced effect in melanoma cell models, while maintaining good systemic safety in vivo. This study provides functional evidence that nanoparticle-mediated radiosensitization is not only determined by a high Z content, but also by tumor-specific metabolic adaptability and the nanoparticle composition. Conclusions. These findings support the rational design of Fe-Gd nanoparticles with optimized therapeutic windows and highlight the importance of metabolic and 3D tissue-relevant models in preclinical evaluation of nanoparticle-mediated radiotherapy. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery, 2nd Edition)
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19 pages, 7529 KB  
Article
Synthesis, Characterisation, and Biological Assessment of Chromium Oxide Nanoparticles Coated with Chia Seed Mucilage Extract
by Sara Lukač, Nina Tomić, Zoran Stojanović, Vladimir Rajić, Nenad Filipović, Maja Jović and Magdalena Stevanović
Pharmaceutics 2026, 18(1), 49; https://doi.org/10.3390/pharmaceutics18010049 - 30 Dec 2025
Viewed by 1464
Abstract
Background/Objectives: Chromium (III) oxide nanoparticles possess unique chemical properties, making them increasingly valuable in pharmaceutical applications, which had been neglected until the last few years. However, their use requires stable dispersion and surface functionalization to ensure their biocompatibility. This study aimed to [...] Read more.
Background/Objectives: Chromium (III) oxide nanoparticles possess unique chemical properties, making them increasingly valuable in pharmaceutical applications, which had been neglected until the last few years. However, their use requires stable dispersion and surface functionalization to ensure their biocompatibility. This study aimed to synthesise, characterise, and determine the biocompatibility and antioxidant properties of chromium oxide nanoparticles coated with a natural, plant-derived stabilising agent: chia seed mucilage extract. Methods: The synthesised nanoparticles were characterised using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared (FTIR) spectroscopy, and laser diffraction scattering particle size analysis (LD-PSA). Biological and biochemical assessments were conducted by the DPPH and FRAP assays to quantify antioxidant scavenging abilities and the Artemia salina lethality test for preliminary biocompatibility evaluation. Results: XRD, FTIR, and EDS confirmed the successful synthesis of pure chromium oxide NPs (CrNPs) and their effective coating by the chia mucilage (CM) extract. SEM analysis determined that a 4:1 mass ratio (CrNPs to CM) produced the most consistent morphology and narrowest size distribution, yielding spherical particles approximately 50 nm in diameter. LD-PSA confirmed the coating and identified a hydrodynamic diameter of approximately 0.110 µm. Biological and biochemical assays showed high antioxidant activity, with over 80% free radical scavenging at concentrations of 250 μg/mL and 50 μg/mL. Furthermore, the biocompatibility assessment showed survival rates above 90% across all tested concentrations. Conclusions: The findings confirm that chia seed mucilage extract can serve as an effective, biocompatible coating agent for chromium (III) oxide nanoparticles. The resulting functionalized particles exhibit exquisite biocompatibility and significant antioxidant potential, supporting their further development for pharmaceutical use. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery, 2nd Edition)
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Review

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53 pages, 2332 KB  
Review
Natural Product-Based Nanomedicine in the Treatment of Breast Cancer
by Kaiyan Su, Yan Li, Dongmei Zhang, Yuxuan Zhou, Jianping Zhang, Hongyan Zhu, Yun Zhao, Cheng Guo and Quanjun Yang
Pharmaceutics 2026, 18(9), 1101; https://doi.org/10.3390/pharmaceutics18091101 - 1 Sep 2026
Viewed by 453
Abstract
Background: Breast cancer remains the most common malignant tumor among women worldwide. Although conventional treatments including surgery, chemotherapy, and radiotherapy are effective, they are confronted with challenges such as tumor heterogeneity, systemic toxicity, and recurrence driven by drug resistance. To overcome these limitations, [...] Read more.
Background: Breast cancer remains the most common malignant tumor among women worldwide. Although conventional treatments including surgery, chemotherapy, and radiotherapy are effective, they are confronted with challenges such as tumor heterogeneity, systemic toxicity, and recurrence driven by drug resistance. To overcome these limitations, natural products have emerged as promising therapeutic alternatives owing to their multi-target efficacy and favorable biocompatibility. However, their clinical translation is still hindered by poor chemical stability, low aqueous solubility, and inadequate bioavailability. Nanodelivery systems offer a transformative solution by enhancing bioavailability and enabling precision targeting through the enhanced permeation and retention effect, thereby widening the therapeutic window and minimizing off-target toxicity. Purpose: This review evaluates diverse nanoparticle-based delivery systems and their targeting mechanisms in natural product-based breast cancer therapy. By examining inherent advantages and translational challenges, this analysis provides critical insights into the clinical development and application of these nanoformulations. Methods: A systematic literature search was performed in PubMed, ScienceDirect, Springer, Taylor & Francis, and Web of Science to identify relevant studies on natural product-based nanoformulations for breast cancer therapy. Results: Natural products exert anti-breast cancer effects through mechanisms such as inducing apoptosis, arresting the cell cycle, inhibiting invasion and metastasis, suppressing angiogenesis, and regulating autophagy. To overcome clinical hurdles, three complementary targeting strategies have been developed: passive, active, and stimuli-responsive targeting. These advances are shifting nanomedicines toward active precision therapy, markedly improving the therapeutic index. With multiple formulations already approved or in clinical pipelines, this field is rapidly progressing from laboratory research to clinical implementation. Conclusions: Natural products possess potent anti-breast cancer effects, and the application of nanodelivery technology effectively overcomes their inherent limitations of poor stability and low bioavailability. Although preliminary findings are promising, large-scale, randomized controlled clinical trials are urgently needed to systematically evaluate their safety, efficacy, and practical potential for clinical translation in breast cancer management. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery, 2nd Edition)
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19 pages, 808 KB  
Review
Albumin Nanoparticles as Multifunctional Carriers for Advanced Therapeutics
by Bogusława Konopska, Janusz Sokołowski, Anna Woźniak, Mikołaj Kondracki, Jakub Federowicz, Wojciech Grodzki, Agnieszka Bronowicka-Szydełko and Katarzyna Madziarska
Pharmaceutics 2026, 18(1), 130; https://doi.org/10.3390/pharmaceutics18010130 - 20 Jan 2026
Cited by 9 | Viewed by 2421
Abstract
Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human [...] Read more.
Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery, 2nd Edition)
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23 pages, 8634 KB  
Review
Recent Advances in Glutathione Depletion-Enhanced Porphyrin-Based nMOFs for Photodynamic Therapy
by Bin Gong, Qiuyun Zhang, Jiayi Chen, Yijie Qu, Xuanxuan Luo, Weiqi Wang and Xiaohua Zheng
Pharmaceutics 2025, 17(2), 244; https://doi.org/10.3390/pharmaceutics17020244 - 12 Feb 2025
Cited by 26 | Viewed by 3283
Abstract
Photodynamic therapy has established itself as a clinical treatment for certain superficial cancers by converting oxygen into cytotoxic singlet oxygen to eradicate cancer cells. Porphyrin-based nanoscale metal–organic frameworks have emerged as promising photosensitive platforms due to their ability to prevent the hydrophobic aggregation [...] Read more.
Photodynamic therapy has established itself as a clinical treatment for certain superficial cancers by converting oxygen into cytotoxic singlet oxygen to eradicate cancer cells. Porphyrin-based nanoscale metal–organic frameworks have emerged as promising photosensitive platforms due to their ability to prevent the hydrophobic aggregation quenching of porphyrin molecules and enhance accumulation at the tumor site, thereby becoming a focal point in photodynamic materials research. However, the elevated levels of glutathione and other reductive substances within cancer cells can alleviate the oxidative stress induced by singlet oxygen from the photodynamic therapy process, thus protecting intracellular biomolecular structures from damage. Consequently, it is crucial to design functionalized nanoplatforms that integrate glutathione depletion with porphyrin-based metal–organic frameworks to significantly boost photodynamic therapy efficacy. Moreover, the excess glutathione within cells can disrupt the structure of porphyrin-based metal–organic frameworks, which not only increases the capacity of porphyrin molecules to generate singlet oxygen upon light exposure but also aids in the recovery of their fluorescence imaging capabilities. Additionally, this specificity minimizes the photosensitizing harm of porphyrin-based metal–organic frameworks to other normal tissues. This review compiles recent advancements in developing porphyrin-based metal–organic frameworks for enhanced phototherapy through glutathione depletion. It aims to promote the further application of porphyrin-based metal–organic frameworks in phototherapy and provide valuable insights for preclinical applications. By highlighting strategies that improve therapeutic outcomes while maintaining safety profiles, this summary seeks to advance the development of more effective and targeted cancer treatments. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery, 2nd Edition)
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