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Biomolecules
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Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier
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Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Bio-Engineered Materials".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 11387

Special Issue Editors

Dr. Yuping Bao

E-Mail Website
Guest Editor
Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, USA
Interests: magnetic nanoparticles; imaging-guided drug delivery; MRI
Special Issues, Collections and Topics in MDPI journals
Dr. Jessica M. Larsen

E-Mail Website
Guest Editor
1. Department of Chemical and Biomolecular Engineering, Clemson University, 105 Sikes Hall, Clemson, SC, USA
2. Department of Bioengineering, Clemson University, 105 Sikes Hall, Clemson, SC, USA
Interests: nanomedicine; drug delivery; brain disease; nerve regeneration; biomaterials; polymers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Significant advancements in nano-based drug delivery systems have offered promising solutions to various challenges in drug delivery such as improved bioavailability, targeted delivery, and reduced side effects. This Special Issue aims to provide a comprehensive overview of the latest developments in this rapidly evolving field. This Special Issue welcomes key themes and contributions that include, but are not limited to, nanoformulations for targeted/precision therapy, controlled/on-demand smart drug delivery systems, nanoformulations for oral or topical delivery, nanosystems across biological barriers, biomimetic nanocarriers, and challenges and future perspectives. In summary, this Special Issue provides a valuable resource for researchers, clinicians, and industry professionals interested in the latest advances and future prospects of nano-based drug delivery systems. By highlighting cutting-edge research and addressing key challenges, it aims to catalyze further innovation in this rapidly expanding field, ultimately contributing to improved therapeutic outcomes for patients.

Dr. Yuping Bao
Dr. Jessica M. Larsen
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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules 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 2700 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

  • targeted drug delivery
  • smart nanoformulation
  • controlled drug release
  • biocompatible nanocarriers
  • extracellular vesicles
  • immunotherapy

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Published Papers (6 papers)

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Research

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16 pages, 4767 KB  
Article
Synthesis of BSA-Coated Iron Oxide Nanoparticles with Size Control for High-Performance T1 Contrast Agents in Magnetic Resonance Imaging
by Bosede Kolawole, Jie Zheng, Dongmei Cao and Yongfeng Zhao
Biomolecules 2026, 16(3), 478; https://doi.org/10.3390/biom16030478 - 23 Mar 2026
Viewed by 583
Abstract
The excellent biocompatibility and favorable physicochemical properties of iron oxide nanoparticles have made them attractive candidates for magnetic resonance imaging. However, it remains challenging to synthesize high-performance T1 contrast agents with controlled sizes and biocompatible coating materials. In this study, we demonstrate [...] Read more.
The excellent biocompatibility and favorable physicochemical properties of iron oxide nanoparticles have made them attractive candidates for magnetic resonance imaging. However, it remains challenging to synthesize high-performance T1 contrast agents with controlled sizes and biocompatible coating materials. In this study, we demonstrate a simple and environmentally friendly approach for synthesizing ultra-small iron oxide nanoparticles using bovine serum albumin (BSA) as a template. Following synthesis, the iron oxide nanoparticles (Fe3O4) were oxidized to Fe2O3 via the addition of hydrogen peroxide, which resulted in enhanced T1-weighted magnetic resonance contrast. The use of BSA not only stabilized the nanoparticles but also enabled precise control over nanoparticle size by adjusting the Fe-to-BSA molar ratio. This method yielded highly uniform and crystalline ultra-small nanoparticles ranging from approximately 3.7 to 7.9 nm in diameter. The T1 contrast performance of the Fe2O3@BSA nanoparticles was evaluated at 3 T magnetic field. Among the synthesized samples, nanoparticles with sizes of 4.6 nm exhibited the strongest T1 contrast enhancement along with low r2/r1 ratios. These features highlight their potential as promising alternatives to gadolinium-based contrast agents. In addition to their superior performance, this synthesis method is low-cost and non-toxic, making it suitable for scalable biomedical applications. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)
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23 pages, 5843 KB  
Article
Electrospun PLA/PVP K90 Biphasic-Release Sublingual Film for Motion Sickness Treatment
by Wenwen Zhang, Qilin Wang, Wei Yi, Hongxi Wang, Deng-Guang Yu and Tao Yi
Biomolecules 2026, 16(3), 363; https://doi.org/10.3390/biom16030363 - 28 Feb 2026
Cited by 5 | Viewed by 666
Abstract
To overcome the limitations of traditional motion sickness medications—slow onset of action, short duration of efficacy, and poor patient compliance—this study employed coaxial electrospinning technology. Poly(lactic acid) (PLA) and polyvinylpyrrolidone K90 (PVP K90) were used as composite carrier materials. The sheath layer is [...] Read more.
To overcome the limitations of traditional motion sickness medications—slow onset of action, short duration of efficacy, and poor patient compliance—this study employed coaxial electrospinning technology. Poly(lactic acid) (PLA) and polyvinylpyrrolidone K90 (PVP K90) were used as composite carrier materials. The sheath layer is composed of highly hydrophilic PVP K90, loaded with the antihistamine diphenhydramine (DPH). The core layer, composed of biodegradable PLA with excellent sustained-release properties, carries the anticholinergic drug scopolamine hydrobromide (SH). This core–sheath nanostructured nanofiber sublingual film delivers dual anti-motion sickness drugs. A series of characterization tests revealed that the sublingual membrane exhibits a linear morphology with a distinct core–shell nanostructure. The drugs DPH and SH are distributed in an amorphous state within the sheath and core layers, respectively. Wetting performance tests indicate that the membrane’s wettability falls between those of monofilament membranes. In vitro drug release experiments revealed that DPH exhibited a “rapid onset + sustained release” biphasic profile, with cumulative release reaching 60% within 2 h and approaching complete release by 10 h, primarily via Fickian diffusion (n = 0.30). SH exhibited prolonged sustained release, approaching complete release at 12 h via non-Fickian diffusion (n = 0.55). Cytotoxicity and vital/necrotic staining experiments mutually corroborated that cell viability remained above 80%, further validating the safety and efficacy of PLA/PVP as a combined drug delivery carrier. This study provides a novel delivery system for motion sickness treatment, offering significant theoretical value and broad clinical application prospects. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)
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15 pages, 2548 KB  
Article
Extracellular Vesicle-Mediated Modulation of Stem-like Phenotype in Breast Cancer Cells under Fluid Shear Stress
by Spenser R. Brown, Margaret E. Radcliffe, Joseph T. Danner, Wilmer J. Andújar Cruz, Kimberly H. Lackey, Han-A Park, Steven T. Weinman and Yonghyun Kim
Biomolecules 2024, 14(7), 757; https://doi.org/10.3390/biom14070757 - 25 Jun 2024
Cited by 2 | Viewed by 3395
Abstract
Circulating tumor cells (CTCs) are some of the key culprits that cause cancer metastasis and metastasis-related deaths. These cells exist in a dynamic microenvironment where they experience fluid shear stress (FSS), and the CTCs that survive FSS are considered to be highly metastatic [...] Read more.
Circulating tumor cells (CTCs) are some of the key culprits that cause cancer metastasis and metastasis-related deaths. These cells exist in a dynamic microenvironment where they experience fluid shear stress (FSS), and the CTCs that survive FSS are considered to be highly metastatic and stem cell-like. Biophysical stresses such as FSS are also known to cause the production of extracellular vesicles (EVs) that can facilitate cell–cell communication by carrying biomolecular cargos such as microRNAs. Here, we hypothesized that physiological FSS will impact the yield of EV production, and that these EVs will have biomolecules that transform the recipient cells. The EVs were isolated using direct flow filtration with and without FSS from the MDA-MB-231 cancer cell line, and the expression of key stemness-related genes and microRNAs was characterized. There was a significantly increased yield of EVs under FSS. These EVs also contained significantly increased levels of miR-21, which was previously implicated to promote metastatic progression and chemotherapeutic resistance. When these EVs from FSS were introduced to MCF-7 cancer cells, the recipient cells had a significant increase in their stem-like gene expression and CD44+/CD24− cancer stem cell-like subpopulation. There was also a correlated increased proliferation along with an increased ATP production. Together, these findings indicate that the presence of physiological FSS can directly influence the EVs’ production and their contents, and that the EV-mediated transfer of miR-21 can have an important role in FSS-existing contexts, such as in cancer metastasis. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)
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Review

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26 pages, 1681 KB  
Review
Biomolecular Interfaces in Targeted Nano-Drug Delivery: Molecular Recognition, Signaling Modulation, and Translational Pathways
by Zeyu Wang, Lixia Dai, Zhen Zhu and Xiaofei Shang
Biomolecules 2026, 16(5), 722; https://doi.org/10.3390/biom16050722 (registering DOI) - 14 May 2026
Abstract
Traditional pharmacotherapy is often constrained by suboptimal bioavailability and systemic toxicity. Biomolecularly inspired nano-drug delivery systems (nano-DDS) have emerged as precise platforms to overcome these barriers by orchestrating molecular interactions at the bio-nano interface. This review systematically evaluates the molecular recognition mechanisms and [...] Read more.
Traditional pharmacotherapy is often constrained by suboptimal bioavailability and systemic toxicity. Biomolecularly inspired nano-drug delivery systems (nano-DDS) have emerged as precise platforms to overcome these barriers by orchestrating molecular interactions at the bio-nano interface. This review systematically evaluates the molecular recognition mechanisms and biochemical principles governing nano-DDS performance. We systematically evaluate how passive targeting relies on the EPR effect—dictated by the nanocarrier’s physicochemical properties—and how active targeting exploits ligand-receptor affinity to enhance cellular uptake. Special emphasis is placed on bioresponsive strategies that utilize pathological cues—such as pH gradients, redox potential, and enzymatic activity—for intelligent, on-demand drug release. Furthermore, we discuss structure-function relationships in lipid, polymeric, and biologically derived systems, highlighting their roles in modulating therapeutic signaling in oncology and inflammatory diseases. Finally, translational hurdles and emerging AI-driven molecular design strategies are critically examined. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)
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23 pages, 610 KB  
Review
Optimizing Extracellular Vesicles for Cardiac Repair Post-Myocardial Infarction: Approaches and Challenges
by Yanling Huang, Han Li, Jinjie Xiong, Xvehua Wang, Jiaxi Lv, Ni Xiong, Qianyi Liu, Lihui Yin, Zhaohui Wang and Yan Wang
Biomolecules 2026, 16(1), 58; https://doi.org/10.3390/biom16010058 - 30 Dec 2025
Viewed by 1094
Abstract
Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)—particularly small EVs (sEVs)—transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and [...] Read more.
Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)—particularly small EVs (sEVs)—transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and remodeling. This review synthesizes recent mechanistic and preclinical evidence on native and engineered EVs for post-MI repair, mapping therapeutic entry points across the MI timeline (acute injury, inflammation, and healing) and comparing EV sources (stem-cell and non-stem-cell), administration routes, and dosing strategies. We highlight engineering approaches—including surface ligands for cardiac homing, rational cargo loading to enhance potency, and biomaterial depots to prolong myocardial residence—that aim to improve tropism, durability, and efficacy. Manufacturing and analytical considerations are discussed in the context of contemporary guidance, with emphasis on identity, purity, and potency assays, as well as safety, immunogenicity, and pharmacology relevant to cardiac populations. Across small- and large-animal models, EV-based interventions have been associated with reduced infarct/scar burden, enhanced vascularization, and improved ventricular function, with representative preclinical studies reporting approximately 25–45% relative reductions in infarct size in rodent and porcine MI models, despite substantial heterogeneity in EV sources, formulations, and outcome reporting that limits cross-study comparability. We conclude that achieving clinical translation will require standardized cardiac-targeting strategies, validated good manufacturing practice (GMP)-compatible manufacturing platforms, and harmonized potency assays, alongside rigorous, head-to-head preclinical designs, to advance EV-based cardiorepair toward clinical testing. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)
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29 pages, 2729 KB  
Review
Applications of Isothermal Titration Calorimetry in Studying Biomimetic Nanocarriers
by Martin Guerrero, Colby Braden and Yuping Bao
Biomolecules 2025, 15(10), 1349; https://doi.org/10.3390/biom15101349 - 23 Sep 2025
Cited by 7 | Viewed by 4508
Abstract
Biomimetic nanocarriers, particularly membrane-based systems, have emerged as promising platforms for drug delivery. A thorough understanding of the molecular interactions that govern their assembly, stability, and cargo-loading efficiency is essential for optimizing their design and performance. Equally important are their interactions with biological [...] Read more.
Biomimetic nanocarriers, particularly membrane-based systems, have emerged as promising platforms for drug delivery. A thorough understanding of the molecular interactions that govern their assembly, stability, and cargo-loading efficiency is essential for optimizing their design and performance. Equally important are their interactions with biological components such as proteins, lipids, nucleotides, and cells, which significantly influence delivery efficacy. Among various techniques for characterizing these nanocarriers, isothermal titration calorimetry (ITC) has proven to be an invaluable tool to study their molecular interactions. ITC enables direct quantification of key thermodynamic parameters, such as binding affinity, stoichiometry, enthalpy, and entropy changes, without the need for molecular labeling or immobilization. This review highlights the application of ITC in the study of biomimetic nanocarriers, focusing on solid lipid nanoparticles, liposomes, extracellular vesicles, cell-derived vesicles and live cells. For each type of nanocarrier, the ITC applications in specific areas and the resulting information are discussed. For example, ITC was used to characterize drug interaction and protein adsorption for solid nanoparticles. In contrast, many aspects of liposomes were explored by ITC, including membrane solubilization and stabilization, peptide interactions, and macromolecule and protein adsorption. Overall, this review aims to provide a conceptual and practical framework for employing ITC in the investigation of biomimetic nanocarrier systems, facilitating their rational design and improved therapeutic performance. Furthermore, the discussion encourages further development of strategies to increase the application in cell-derived vesicles and live cells. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)
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