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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 26825

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Dr. Hyun-Ouk Kim

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Department of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea
Interests: cancer; infectious diseases; nanoencapsulation; nanomedicine; nanoparticles; new drug delivery systems; polymersome; theragnosis
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Special Issue Information

Dear Colleagues,

Cancer is a major global health issue. Indeed, despite significant progress made in the fields of cancer research and treatment, there remains a need for more effective and precise diagnostic tools and treatment options. Nanotechnology, the manipulation of materials at the nanoscale level, has the potential to revolutionize cancer care by offering innovative approaches for prevention, diagnosis, and treatment. Nanoparticles can be engineered to selectively target cancer cells while minimizing side effects, whether as drug carriers or imaging agents. In cancer prevention, nanotechnology may help to reduce the incidence of the disease by developing novel approaches to address risk factors and early detection. The impact of nanotechnology in cancer care has shown promising results in preclinical and clinical studies. However, further research and development are necessary to realize its full potential in cancer care. Nanotechnology presents a unique opportunity to develop more effective and precise cancer therapies, which may in turn lead to better outcomes for patients.

We look forward to receiving your contributions.

Dr. Hyun-Ouk Kim
Guest Editor

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Keywords

nanoparticles
drug delivery
biosensors
imaging
theragnosis

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Published Papers (10 papers)

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Research

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19 pages, 8646 KiB

Open AccessArticle

Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study

by Silviu Iulian Filipiuc, Natalia Simionescu, Gabriela Dumitrița Stanciu, Adina Coroaba, Narcisa Laura Marangoci, Leontina Elena Filipiuc, Mariana Pinteala, Cristina Mariana Uritu and Bogdan Ionel Tamba

Pharmaceutics 2025, 17(3), 307; https://doi.org/10.3390/pharmaceutics17030307 - 27 Feb 2025

Viewed by 857

Abstract

Objectives: This work aimed to develop and investigate liposomes incorporating Rhein (Lip-Rh) into the liposomal membrane to enhance the compound’s water solubility and oral bioavailability. Methods: Liposomes were produced by the thin lipid film technique, with a phosphatidylcholine-to-cholesterol molar ratio of 5:1, dissolved in chloroform and methanol, and thereafter hydrated with ultrapure water and subjected to sonication. The resultant liposomes were studied from a physicochemical perspective using DLS, zeta potential, STEM, UV–Vis, and fluorescence spectroscopies, while oral bioavailability was assessed by fluorescence imaging. Additionally, cell viability assays were performed on tumour cells (MCF-7) in comparison to normal cells (HGFs). Results: The resultant nanoparticles exhibited relatively uniform sizes and narrow size distribution. In vivo fluorescence imaging studies performed on Wistar rats demonstrated significantly enhanced oral bioavailability for Lip-Rh, with rapid absorption into the bloodstream observed one hour after administration, in contrast to the free compound dissolved in vegetable oil. Cell viability assays demonstrated higher cytotoxicity of Lip-Rh towards MCF-7 cells compared to HGF cells, highlighting the selective therapeutic potential of the product. Moreover, we determined that the optimal dose of Rhein per kilogram of body weight, when encapsulated in liposomes, is approximately 2.5 times less than when Rhein is delivered in its unencapsulated form. Conclusions: Lip-Rh is a promising candidate for oncological treatments, presenting three key advantages: increased cytotoxicity towards tumour cells, protection of normal tissues, and the practicality of oral delivery. Additional investigation is required to explore its application in anticancer therapy, whether as monotherapy or as a complementary treatment. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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17 pages, 4085 KiB

Open AccessArticle

Charge-Complementary Polymersomes for Enhanced mRNA Delivery

by HakSeon Kim, Yu-Rim Ahn, Minse Kim, Jaewon Choi, SoJin Shin and Hyun-Ouk Kim

Pharmaceutics 2023, 15(12), 2781; https://doi.org/10.3390/pharmaceutics15122781 - 15 Dec 2023

Cited by 2 | Viewed by 2199

Abstract

Messenger RNA (mRNA) therapies have emerged as potent and personalized alternatives to conventional DNA-based therapies. However, their therapeutic potential is frequently constrained by their molecular instability, susceptibility to degradation, and inefficient cellular delivery. This study presents the nanoparticle “ChargeSome” as a novel solution. ChargeSomes are designed to protect mRNAs from degradation by ribonucleases (RNases) and enable cell uptake, allowing mRNAs to reach the cytoplasm for protein expression via endosome escape. We evaluated the physicochemical properties of ChargeSomes using ¹H nuclear magnetic resonance, Fourier-transform infrared, and dynamic light scattering. ChargeSomes formulated with a 9:1 ratio of mPEG-b-PLL to mPEG-b-PLL-SA demonstrated superior cell uptake and mRNA delivery efficiency. These ChargeSomes demonstrated minimal cytotoxicity in various in vitro structures, suggesting their potential safety for therapeutic applications. Inherent pH sensitivity enables precise mRNA release in acidic environments and structurally protects the encapsulated mRNA from external threats. Their design led to endosome rupture and efficient mRNA release into the cytoplasm by the proton sponge effect in acidic endosome environments. In conclusion, ChargeSomes have the potential to serve as effective secure mRNA delivery systems. Their combination of stability, protection, and delivery efficiency makes them promising tools for the advancement of mRNA-based therapeutics and vaccines. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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13 pages, 3330 KiB

Open AccessArticle

Prevention of Colitis-Associated Cancer via Oral Administration of M13-Loaded Lipid Nanoparticles

by Dingpei Long, Zahra Alghoul, Junsik Sung, Chunhua Yang and Didier Merlin

Pharmaceutics 2023, 15(9), 2331; https://doi.org/10.3390/pharmaceutics15092331 - 16 Sep 2023

Cited by 2 | Viewed by 6460

Abstract

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease, is known to increase the risk of colitis-associated cancer (CAC). CAC has been found to be unresponsive to standard chemotherapy regimens, and the current treatments do not utilize effective small-molecule drugs and colon-targeted delivery systems. Previous studies indicated that the M13–nano-liposome (NL) formulation can effectively target the colon and reshape the gut microbiota in ex vivo cultures, generating altered microbial metabolites that can efficiently prevent chronic UC. In this study, we tested the cancer cell uptake ability of the NL formulation and investigated the potential of the M13–NL formulation to prevent CAC in the azoxymethane (AOM)-exposed IL10^−/− mouse model. Our findings demonstrate that oral administration of M13–NL prevents tumor development in AOM-exposed IL10^−/− mice, suggesting that M13–NL is a promising oral drug formulation for preventing CAC. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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12 pages, 1685 KiB

Open AccessArticle

Overcoming Resistance to Immune Checkpoint Inhibitor Therapy Using Calreticulin-Inducing Nanoparticle

by Sri Vidhya Chandrasekar, Akansha Singh and Ashish Ranjan

Pharmaceutics 2023, 15(6), 1693; https://doi.org/10.3390/pharmaceutics15061693 - 9 Jun 2023

Cited by 3 | Viewed by 2316

Abstract

Nanoparticles (NPs) have the ability to transform poorly immunogenic tumors into activated ‘hot’ targets. In this study, we investigated the potential of a liposome-based nanoparticle (CRT-NP) expressing calreticulin as an in-situ vaccine to restore sensitivity to anti-CTLA4 immune checkpoint inhibitor (ICI) in CT26 colon tumors. We found that a CRT-NP with a hydrodynamic diameter of approximately 300 nm and a zeta potential of approximately +20 mV induced immunogenic cell death (ICD) in CT-26 cells in a dose-dependent manner. In the mouse model of CT26 xenograft tumors, both CRT-NP and ICI monotherapy caused moderate reductions in tumor growth compared to the untreated control group. However, the combination therapy of CRT-NP and anti-CTLA4 ICI resulted in remarkable suppression of tumor growth rates (>70%) compared to untreated mice. This combination therapy also reshaped the tumor microenvironment (TME), achieving the increased infiltration of antigen-presenting cells (APCs) such as dendritic cells and M1 macrophages, as well as an abundance of T cells expressing granzyme B and a reduction in the population of CD4+ Foxp3 regulatory cells. Our findings indicate that CRT-NPs can effectively reverse immune resistance to anti-CTLA4 ICI therapy in mice, thereby improving the immunotherapeutic outcome in the mouse model. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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13 pages, 3904 KiB

Open AccessArticle

Development of a Gold Nanoparticle-Linked Immunosorbent Assay of Staphylococcal Enterotoxin B Detection with Extremely High Sensitivity by Determination of Gold Atom Content Using Graphite Furnace Atomic Absorption Spectrometry

by Chaojun Song, Yutao Liu, Jinwei Hu, Yupu Zhu, Zhengjun Ma, Jiayue Xi, Minxuan Cui, Leiqi Ren and Li Fan

Pharmaceutics 2023, 15(5), 1493; https://doi.org/10.3390/pharmaceutics15051493 - 13 May 2023

Cited by 2 | Viewed by 1909

Abstract

Highly sensitive staphylococcal enterotoxin B (SEB) assay is of great importance for the prevention of toxic diseases caused by SEB. In this study, we present a gold nanoparticle (AuNP)-linked immunosorbent assay (ALISA) for detecting SEB in a sandwich format using a pair of SEB specific monoclonal antibodies (mAbs) performed in microplates. First, the detection mAb was labeled with AuNPs of different particle sizes (15, 40 and 60 nm). Then the sandwich immunosorbent assay for SEB detection was performed routinely in a microplate except for using AuNPs-labeled detection mAb. Next, the AuNPs adsorbed on the microplate were dissolved with aqua regia and the content of gold atoms was determined by graphite furnace atomic absorption spectrometry (GFAAS). Finally, a standard curve was drawn of the gold atomic content against the corresponding SEB concentration. The detection time of ALISA was about 2.5 h. AuNPs at 60 nm showed the highest sensitivity with an actual measured limit of detection (LOD) of 0.125 pg/mL and a dynamic range of 0.125–32 pg/mL. AuNPs at 40 nm had an actual measured LOD of 0.5 pg/mL and a dynamic range of 0.5 to 128 pg/mL. AuNPs at 15 nm had an actual measured LOD of 5 pg/mL, with a dynamic range of 5–1280 pg/mL. With detection mAb labeled with AuNPs at 60 nm, ALISA’s intra- and interassay coefficient variations (CV) at three concentrations (2, 8, and 20 pg/mL) were all lower than 12% and the average recovery level was ranged from 92.7% to 95.0%, indicating a high precision and accuracy of the ALISA method. Moreover, the ALISA method could be successfully applied to the detection of various food, environmental, and biological samples. Therefore, the successful establishment of the ALISA method for SEB detection might provide a powerful tool for food hygiene supervision, environmental management, and anti-terrorism procedures and this method might achieve detection and high-throughput analysis automatically in the near future, even though GFAAS testing remains costly at present. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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19 pages, 847 KiB

Open AccessReview

Targeted Drug Delivery to the Spleen and Its Implications for the Prevention and Treatment of Cancer

by Ikramy A. Khalil, Ahmed Faheem and Mohamed El-Tanani

Pharmaceutics 2025, 17(5), 651; https://doi.org/10.3390/pharmaceutics17050651 - 15 May 2025

Viewed by 208

Abstract

The spleen, the largest secondary lymphoid organ, plays several vital roles in the body, including blood filtration, hematopoiesis, and immune regulation. Despite its importance, the spleen has not received substantial attention as a target organ for drug delivery. Most systemically administered colloidal and particulate drug carriers are cleared from the blood by the liver and spleen, making these two organs potential targets for drug accumulation. While various systems have been developed to target the liver, there is an urgent need to design spleen-targeted drug delivery systems that can evade clearance and degradation while delivering drugs efficiently to their target cells in the spleen. Targeting the spleen holds great potential for the treatment of a range of diseases, including blood disorders, immune and inflammatory diseases, infectious diseases, and cancer. It is also crucial for the development of effective vaccines. In this review, we explore different approaches used to target the spleen after systemic administration, and we discuss the factors that shift the biodistribution of drug carriers from the liver to the spleen. We focus on cell-specific delivery within the spleen, strategies to avoid degradation, and methods to achieve the efficient intracellular delivery of various drugs and genes. We also highlight the therapeutic implications of spleen-targeted drug delivery systems, particularly for the prevention and treatment of cancer. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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41 pages, 4854 KiB

Open AccessReview

Unlocking the Potential of Ganoderma lucidum (Curtis): Botanical Overview, Therapeutic Applications, and Nanotechnological Advances

by Ana Eira, Maria Beatriz S. Gonçalves, Yannick Stéphane Fotsing Fongang, Cátia Domingues, Ivana Jarak, Filipa Mascarenhas-Melo and Ana Figueiras

Pharmaceutics 2025, 17(4), 422; https://doi.org/10.3390/pharmaceutics17040422 - 26 Mar 2025

Viewed by 1007

Abstract

Background: Ganoderma lucidum (GL), commonly known as the “Lingzhi” or “Reishi” mushroom, has long been recognized for its potential health benefits and medicinal properties in traditional Chinese medicine. The unique potential combination of bioactive compounds present in GL, such as triterpenoids, polysaccharides, and peptides, has inspired interest in leveraging their therapeutic potential In recent years, the emerging field of nanotechnology has opened up new possibilities for using the remarkable properties of GL at the nanoscale. Objetive: The main objective of this review is to explore the unique potential of GL in traditional and innovative therapies, particularly in cancer treatment, and to assess how nanotechnology-based strategies can enhance its therapeutic applications.is to explore. Results: Nanotechnology-based strategies have been investigated for the efficient extraction and purification of bioactive compounds from GL. Additionally, nanocarriers and nanoformulations have been developed to protect these sensitive bioactive compounds from degradation, ensuring their stability during storage and transportation. The use of GL-based nanomaterials has shown promising results in several biomedical applications, namely due to their anticancer activity by targeting cancer cells, inducing apoptosis, and inhibiting tumor growth. Conclusions: The combination of GL and nanotechnology presents an exciting frontier in the development of novel therapeutic and biomedical applications. Nevertheless, further research and development in this interdisciplinary field are warranted to fully exploit the synergistic benefits offered by GL and nanotechnology. Future prospects include the development of robust clinical trials focused on GL nanotechnology-based cancer therapies to clarify mechanisms of actions and optimize formulations, ultimately leading to innovative solutions for human health and well-being. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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16 pages, 6332 KiB

Open AccessEditor’s ChoiceReview

Recent Advances in Drug Delivery Strategies for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: A Brief Review from 2018 to 2024

by Feng Qu, Saloni Darji and David H. Thompson

Pharmaceutics 2024, 16(9), 1154; https://doi.org/10.3390/pharmaceutics16091154 - 30 Aug 2024

Cited by 5 | Viewed by 2935

Abstract

High-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) is a condition that is typically treated with Bacillus Calmette–Guérin (BCG) therapy. Unfortunately, NMIBC is characterized by high recurrence, with a significant percentage of BCG patients ultimately requiring radical cystectomy. As a consequence, the development of effective new therapies to avoid RC has become a rapidly evolving field to address this unmet clinical need. To date, three biologics—Keytruda, Adstiladrin, and Anktiva—have been approved by the FDA, and multiple drug modalities, particularly gene therapies, have shown promising results in clinical trials. Advances in drug delivery strategies, such as targeted delivery, sustained release, and permeabilization of protective layers, are critical in overcoming the challenges posed by therapeutic intervention in bladder cancer. This review focuses on high-risk BCG-unresponsive NMIBC therapies that have been or are currently being investigated in clinical trials, offering a broad overview of the delivery system designs and up-to-date clinical outcomes that have been reported as of July 2024. It aims to inform the development of future drug delivery systems for second-line therapies in high-risk BCG-unresponsive NMIBC. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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46 pages, 8589 KiB

Open AccessReview

Advances in Light-Responsive Smart Multifunctional Nanofibers: Implications for Targeted Drug Delivery and Cancer Therapy

by Ahmed M. Agiba, Nihal Elsayyad, Hala N. ElShagea, Mahmoud A. Metwalli, Amin Orash Mahmoudsalehi, Saeed Beigi-Boroujeni, Omar Lozano, Alan Aguirre-Soto, Jose Luis Arreola-Ramirez, Patricia Segura-Medina and Raghda Rabe Hamed

Pharmaceutics 2024, 16(8), 1017; https://doi.org/10.3390/pharmaceutics16081017 - 31 Jul 2024

Cited by 5 | Viewed by 3838

Abstract

Over the last decade, scientists have shifted their focus to the development of smart carriers for the delivery of chemotherapeutics in order to overcome the problems associated with traditional chemotherapy, such as poor aqueous solubility and bioavailability, low selectivity and targeting specificity, off-target drug side effects, and damage to surrounding healthy tissues. Nanofiber-based drug delivery systems have recently emerged as a promising drug delivery system in cancer therapy owing to their unique structural and functional properties, including tunable interconnected porosity, a high surface-to-volume ratio associated with high entrapment efficiency and drug loading capacity, and high mass transport properties, which allow for controlled and targeted drug delivery. In addition, they are biocompatible, biodegradable, and capable of surface functionalization, allowing for target-specific delivery and drug release. One of the most common fiber production methods is electrospinning, even though the relatively two-dimensional (2D) tightly packed fiber structures and low production rates have limited its performance. Forcespinning is an alternative spinning technology that generates high-throughput, continuous polymeric nanofibers with 3D structures. Unlike electrospinning, forcespinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This review addresses current trends and potential applications of light-responsive and dual-stimuli-responsive electro- and forcespun smart nanofibers in cancer therapy, with a particular emphasis on functionalizing nanofiber surfaces and developing nano-in-nanofiber emerging delivery systems for dual-controlled drug release and high-precision tumor targeting. In addition, the progress and prospective diagnostic and therapeutic applications of light-responsive and dual-stimuli-responsive smart nanofibers are discussed in the context of combination cancer therapy. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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24 pages, 11452 KiB

Open AccessReview

Nano/Micromotors for Cancer Diagnosis and Therapy: Innovative Designs to Improve Biocompatibility

by Jiahuan Zheng, Rui Huang, Zhexuan Lin, Shaoqi Chen and Kaisong Yuan

Pharmaceutics 2024, 16(1), 44; https://doi.org/10.3390/pharmaceutics16010044 - 27 Dec 2023

Cited by 5 | Viewed by 3324

Abstract

Nano/micromotors are artificial robots at the nano/microscale that are capable of transforming energy into mechanical movement. In cancer diagnosis or therapy, such “tiny robots” show great promise for targeted drug delivery, cell removal/killing, and even related biomarker sensing. Yet biocompatibility is still the most critical challenge that restricts such techniques from transitioning from the laboratory to clinical applications. In this review, we emphasize the biocompatibility aspect of nano/micromotors to show the great efforts made by researchers to promote their clinical application, mainly including non-toxic fuel propulsion (inorganic catalysts, enzyme, etc.), bio-hybrid designs, ultrasound propulsion, light-triggered propulsion, magnetic propulsion, dual propulsion, and, in particular, the cooperative swarm-based strategy for increasing therapeutic effects. Future challenges in translating nano/micromotors into real applications and the potential directions for increasing biocompatibility are also described. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Cancer)

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