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25 pages, 1839 KiB  
Review
Burkholderia Phages and Control of Burkholderia-Associated Human, Animal, and Plant Diseases
by Bingjie Wang, Jiayi Zhang, Lei Chen, Munazza Ijaz, Ji’an Bi, Chenhao Li, Daixing Dong, Yanxin Wang, Bin Li, Jinyan Luo and Qianli An
Microorganisms 2025, 13(8), 1873; https://doi.org/10.3390/microorganisms13081873 - 11 Aug 2025
Abstract
Gram-negative Burkholderia bacteria are known for causing diseases in humans, animals, and plants, and high intrinsic resistance to antibiotics. Phage therapy is a promising alternative to control multidrug-resistant bacterial pathogens. Here, we present an overview of Burkholderia phage characteristics, host specificity, genomic classification, [...] Read more.
Gram-negative Burkholderia bacteria are known for causing diseases in humans, animals, and plants, and high intrinsic resistance to antibiotics. Phage therapy is a promising alternative to control multidrug-resistant bacterial pathogens. Here, we present an overview of Burkholderia phage characteristics, host specificity, genomic classification, and therapeutic potentials across medical, veterinary, and agricultural systems. We evaluate the efficacy and limitations of current phage candidates, the biological and environmental barriers of phage applications, and the phage cocktail strategy. We highlight the innovations on the development of targeted phage delivery systems and the transition from the exploration of clinical phage therapy to plant disease management, advocating integrated disease control strategies. Full article
(This article belongs to the Special Issue Phage–Bacteria Interplay: Phage Biology and Phage Therapy)
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40 pages, 2575 KiB  
Review
Nanoparticle-Based Delivery Strategies for Combating Drug Resistance in Cancer Therapeutics
by Seohyun Park, Guo-Liang Lu, Yi-Chao Zheng, Emma K. Davison and Yan Li
Cancers 2025, 17(16), 2628; https://doi.org/10.3390/cancers17162628 - 11 Aug 2025
Abstract
Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of [...] Read more.
Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of addressing these challenges by enhancing intracellular drug accumulation, enabling targeted delivery and facilitating stimuli-responsive and controlled release. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying MDR and critically examines recent advances in nanoparticle strategies developed to overcome it. Various nanoparticle designs are analysed in terms of their structural and functional features, including surface modifications, active targeting ligands and responsiveness to tumour-specific cues. Particular emphasis is placed on the co-delivery of chemotherapeutic agents with gene regulators, such as siRNA, and the use of nanoparticles to deliver CRISPR/Cas9 gene editing tools as a means of re-sensitising resistant cancer cells. While significant progress has been made in preclinical settings, challenges such as tumour heterogeneity, limited clinical translation and immune clearance remain. Future directions include the integration of precision nanomedicine, scalable manufacturing and non-viral genome editing platforms. Collectively, nanoparticle-based drug delivery systems offer a multifaceted approach to combat MDR and hold great promise for improving therapeutic outcomes in resistant cancers. Full article
5 pages, 163 KiB  
Editorial
Editorial on Special Issue: “Advances in Nanotechnology-Based Drug Delivery Systems”
by Carla Serri
Pharmaceutics 2025, 17(8), 1038; https://doi.org/10.3390/pharmaceutics17081038 - 10 Aug 2025
Abstract
Nanotechnology enables the design and application of nanostructures to improve drug delivery by modulating release, enhancing solubility, and increasing bioavailability of poorly soluble APIs, while reducing side effects. This Special Issue includes original research articles and reviews on innovative nanocarriers, such as liposomes, [...] Read more.
Nanotechnology enables the design and application of nanostructures to improve drug delivery by modulating release, enhancing solubility, and increasing bioavailability of poorly soluble APIs, while reducing side effects. This Special Issue includes original research articles and reviews on innovative nanocarriers, such as liposomes, metal and carbon nanoparticles, nanocrystals, and polymeric systems, utilizing sustainable and environmentally friendly synthesis methods. Special emphasis is placed on formulation strategies for encapsulating biological macromolecules, advancing the development of efficient, eco-friendly delivery platforms. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
30 pages, 4173 KiB  
Review
Recent Advances in Nanomedicine: Cutting-Edge Research on Nano-PROTAC Delivery Systems for Cancer Therapy
by Xiaoqing Wu, Yueli Shu, Yao Zheng, Peichuan Zhang, Hanwen Cong, Yingpei Zou, Hao Cai and Zhengyu Zha
Pharmaceutics 2025, 17(8), 1037; https://doi.org/10.3390/pharmaceutics17081037 - 10 Aug 2025
Abstract
Proteolysis-targeting chimeras (PROTACs) selectively degrade target proteins by recruiting intracellular E3 ubiquitin ligases, overcoming the limitations of traditional small-molecule inhibitors that merely block protein function. This approach has garnered significant interest in precision cancer therapy. However, the clinical translation of PROTACs is hindered [...] Read more.
Proteolysis-targeting chimeras (PROTACs) selectively degrade target proteins by recruiting intracellular E3 ubiquitin ligases, overcoming the limitations of traditional small-molecule inhibitors that merely block protein function. This approach has garnered significant interest in precision cancer therapy. However, the clinical translation of PROTACs is hindered by their typically high molecular weight, poor membrane permeability, and suboptimal pharmacokinetic properties. Nanodrug delivery technologies represent a promising approach to overcome the limitations of PROTACs. By encapsulating, conjugating, or integrating PROTACs into functionalized nanocarriers, these systems can substantially enhance solubility and biostability, enable tumor-targeted and stimuli-responsive delivery, and thereby effectively alleviate the “hook effect” and minimize off-target toxicity. This review systematically outlines the primary design strategies for current nano-PROTAC delivery systems, including physical encapsulation, chemical conjugation, carrier-free self-assembly systems, and intelligent “split-and-mix” delivery platforms. We provide an overview and evaluation of recent advances in diverse nanomaterial carriers—such as lipid-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, biological carriers, and hybrid nanoparticles—highlighting their synergistic therapeutic potential for PROTACs delivery. The clinical translation prospects of these innovative systems are also discussed. This comprehensive analysis aims to deepen the understanding of this rapidly evolving field, address current challenges and opportunities, promote the advancement of nano-PROTACs, and offer insights into their future development. Full article
(This article belongs to the Special Issue Prodrug Strategies for Enhancing Drug Stability and Pharmacokinetics)
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28 pages, 896 KiB  
Review
Nanoparticles as an Encouraging Therapeutic Approach to Alzheimer’s Disease
by Joanna Koga-Batko, Katarzyna Antosz-Popiołek, Hanna Nowakowska, Marta Błażejewska, Eunika Milena Kowalik, Jan Aleksander Beszłej and Jerzy Leszek
Int. J. Mol. Sci. 2025, 26(16), 7725; https://doi.org/10.3390/ijms26167725 - 10 Aug 2025
Abstract
Alzheimer’s disease (AD) is an irreversible neurodegenerative disease of the central nervous system, responsible for 60–80% of dementia. Its pathogenesis is mainly based on the accumulation of beta-amyloid and tau proteins. Current pharmacological treatment includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and monoclonal antibodies. [...] Read more.
Alzheimer’s disease (AD) is an irreversible neurodegenerative disease of the central nervous system, responsible for 60–80% of dementia. Its pathogenesis is mainly based on the accumulation of beta-amyloid and tau proteins. Current pharmacological treatment includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and monoclonal antibodies. However, their effect is limited by the blood–brain barrier (BBB). A new and promising way for different drugs to cross the BBB is the use of nanoparticles such as liposomes, micelles, solid lipid nanocarriers, polymeric nanoparticles, dendrimers, nanoemulsions, and inorganic nanoparticles as their carriers. Additionally, some nanoparticles present anti-inflammatory or neuroprotective effects. Some of them can also be used to treat cerebral amyloid angiopathy (CAA) by aiming at amyloid deposits in brain arterioles. All the properties of nanoparticles listed and discussed in the article allow us to hope that there will be more effective treatment in the future, which is extremely important as the number of patients with AD is still growing. Full article
(This article belongs to the Section Molecular Nanoscience)
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22 pages, 2040 KiB  
Article
Açaí-Loaded Nanoemulsion: Synthesis, Characterization, and In Vitro Safety Profile
by Samantha Nunes de Godoi, Diulie Valente de Souza, Tuyla Fontana, Lauren Pappis, Fernanda Reis Favarin, Giovana Kolinski Cossettin Bonazza, Carolina Bordin Davidson, Sabrina Somacal, Tatiana Emanuelli, Fernando Dal Pont Morisso, André Gündel, Diogo André Pilger, Alencar Kolinski Machado and Aline Ferreira Ourique
Appl. Sci. 2025, 15(16), 8822; https://doi.org/10.3390/app15168822 - 10 Aug 2025
Abstract
Background: Natural products have been used worldwide as alternatives to treat or prevent different chronic diseases. Euterpe oleracea Mart. (açaí) has bioactive molecules in its chemical matrix, such as epicatechin, apigenin, and cyanidin-3-O-rutinoside. These molecules guarantee açaí’s antioxidant, anti-inflammatory, and antitumor potential. Açaí’s [...] Read more.
Background: Natural products have been used worldwide as alternatives to treat or prevent different chronic diseases. Euterpe oleracea Mart. (açaí) has bioactive molecules in its chemical matrix, such as epicatechin, apigenin, and cyanidin-3-O-rutinoside. These molecules guarantee açaí’s antioxidant, anti-inflammatory, and antitumor potential. Açaí’s chemical matrix is susceptible to degradation. Nanocarriers are appropriate to use with NP. The aim of this study was to produce, characterize, and analyze the in vitro safety profile of a nanoemulsion (NE) containing açaí extract. Methods: Different NEs were prepared with açaí extract (0.83–20 mg/mL). A characterization was performed considering physical–chemical parameters and a morphological analysis. The most stable NE was evaluated for in vitro safety in fibroblasts. Fibroblasts were exposed to a concentration curve of NEs for 24 h. Cellular viability and proliferation, the levels of nitric oxide, reactive oxygen species (ROS), and the release of dsDNA were measured. Possible DNA damage was also measured. Results: It was possible to determine that the NE with 4 mg/mL of açaí extract was the most stable under refrigeration, presenting a favorable in vitro safety profile since fibroblasts kept their homeostasis aspects under most of the concentrations tested as well as their DNA integrity. Conclusion: The obtained results show that a stable NE was produced, maintaining the NP antioxidant capacity and non-toxic effects in fibroblasts. Full article
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28 pages, 1017 KiB  
Review
Naringin and Naringenin in Liver Health: A Review of Molecular and Epigenetic Mechanisms and Emerging Therapeutic Strategies
by Roberto Flores-Peña, Hugo Christian Monroy-Ramirez, Fernando Caloca-Camarena, Scarlet Arceo-Orozco, Jorge Alejandro Salto-Sevilla, Marina Galicia-Moreno and Juan Armendariz-Borunda
Antioxidants 2025, 14(8), 979; https://doi.org/10.3390/antiox14080979 - 10 Aug 2025
Abstract
Liver diseases have become a significant global health concern, driving increased interest in naturally occurring compounds as adjunctive treatments for managing these conditions. Flavonoids, a class of natural polyphenols found in plants and fruits, offer a broad spectrum of potential health benefits due [...] Read more.
Liver diseases have become a significant global health concern, driving increased interest in naturally occurring compounds as adjunctive treatments for managing these conditions. Flavonoids, a class of natural polyphenols found in plants and fruits, offer a broad spectrum of potential health benefits due to their applications in nutraceuticals, pharmaceuticals, and cosmetics. Among them, naringin (NARI) and naringenin (NAR), which are abundant in citrus fruits, have attracted considerable attention. Numerous studies have investigated the therapeutic effects of NARI and NAR across different stages of liver disease. This review highlights recent research on the impact of these flavonoids in alcohol-related liver disease and metabolic dysfunction-associated fatty liver disease (MASLD). It also explores the molecular mechanisms and epigenetic modifications through which NARI and NAR contribute to preventing liver disease progression. Finally, this work discusses recent progresses and future perspectives, emphasizing the role of innovative nanocarriers, nanoparticles, and drug delivery strategies in enhancing the efficacy and bioavailability of these promising compounds to improve liver health. Full article
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25 pages, 4674 KiB  
Review
Research Progress on Icariin Promoting Bone Injury Repair and Regeneration
by Weijian Hu, Yameng Si, Xin Xie and Jiabin Xu
Pharmaceuticals 2025, 18(8), 1174; https://doi.org/10.3390/ph18081174 - 8 Aug 2025
Viewed by 242
Abstract
Icariin (ICA) is a bioactive flavonoid compound extracted from Epimedium plants. In recent years, it has attracted significant research interest in the field of bone tissue repair due to its pharmacological effects via multiple targets and pathways. Studies have shown that ICA promotes [...] Read more.
Icariin (ICA) is a bioactive flavonoid compound extracted from Epimedium plants. In recent years, it has attracted significant research interest in the field of bone tissue repair due to its pharmacological effects via multiple targets and pathways. Studies have shown that ICA promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and enhances bone matrix formation by regulating signaling pathways such as Akt and Wnt/β-catenin. It concurrently inhibits osteoclast activity to maintain the balance of bone remodeling, thereby simultaneously stimulating new bone regeneration and suppressing bone resorption. At the same time, ICA exerts potent anti-inflammatory and antioxidant effects and promotes angiogenesis, improving the local microenvironment of bone injury and significantly facilitating the regeneration of bone and cartilage tissues. Additionally, ICA exhibits notable protective effects in multiple organ systems including the cardiovascular, hepatic, renal, and nervous systems. Specifically, ICA reduces cardiomyocyte apoptosis and fibrosis to preserve cardiac function, improves hepatic metabolic function and alleviates oxidative stress, attenuates renal inflammation and fibrosis, and—through neuroprotective actions—reduces neuroinflammation and promotes neuronal survival. These multi-organ effects help optimize the systemic environment for bone healing. However, ICA faces significant pharmacokinetic challenges. It has low oral bioavailability (due to poor absorption and extensive first-pass metabolism) as well as a short half-life. Consequently, maintaining effective drug concentrations in vivo is difficult, which limits its therapeutic efficacy and impedes clinical translation. To fully realize its regenerative potential, advanced drug delivery strategies (e.g., nanocarrier-based delivery systems) are being explored to enhance ICA’s bioavailability and prolong its duration of action. Overall, ICA’s multi-modal actions on bone cells, the immune microenvironment, and systemic factors make it a promising multi-target agent for bone regeneration. Addressing its pharmacokinetic limitations through optimized delivery and conducting further clinical studies will be crucial to realize its full therapeutic potential. This review provides a comprehensive overview of recent advances and challenges in translating ICA’s benefits into orthopedic therapy. Full article
(This article belongs to the Section Natural Products)
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41 pages, 2949 KiB  
Review
Nanocarriers Containing Curcumin and Derivatives for Arthritis Treatment: Mapping the Evidence in a Scoping Review
by Beatriz Yurie Sugisawa Sato, Susan Iida Chong, Nathalia Marçallo Peixoto Souza, Raul Edison Luna Lazo, Roberto Pontarolo, Fabiane Gomes de Moraes Rego, Luana Mota Ferreira and Marcel Henrique Marcondes Sari
Pharmaceutics 2025, 17(8), 1022; https://doi.org/10.3390/pharmaceutics17081022 - 6 Aug 2025
Viewed by 181
Abstract
Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water [...] Read more.
Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article
(This article belongs to the Special Issue Advances in Polymer-Based Devices and Platforms for Pain Management)
19 pages, 13597 KiB  
Systematic Review
Current Research Trends and Hotspots in Radiotherapy Combined with Nanomaterials for Cancer Treatment: A Bibliometric and Visualization Analysis
by Muyasha Abulimiti, Shiqin Dai, Ebara Mitsuhiro, Yu Sugawara, Yinuo Li, Hideyuki Sakurai and Yoshitaka Matsumoto
Nanomaterials 2025, 15(15), 1205; https://doi.org/10.3390/nano15151205 - 6 Aug 2025
Viewed by 290
Abstract
This study investigated the evolving trends, current research hotspots, and future directions of radiotherapy combined with nanobiomaterials through a bibliometric analysis. Publications related to nanobiomaterials used in radiotherapy between 2004 and 2024 were retrieved from the Web of Science Core Collection database and [...] Read more.
This study investigated the evolving trends, current research hotspots, and future directions of radiotherapy combined with nanobiomaterials through a bibliometric analysis. Publications related to nanobiomaterials used in radiotherapy between 2004 and 2024 were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, R, and CiteSpace. China emerged as the leading contributor, accounting for 1051 publications (50.41%), followed by the USA. Liu Zhuang is the most productive author in this field. American Chemical Society (ACS) Nano published the most influential articles and accumulated the highest number of citations. Advanced Targeted Therapies in Cancer: Drug Nanocarriers, the Future of Chemotherapy was the most cited, with 1255 citations. Citation bursts have revealed emerging research trends in targeted delivery, cellular studies, co-delivery strategies, immunogenic cell death, polymeric nanoparticles, tumor research, and drug delivery systems, indicating potential avenues for future research. Over the past two decades, nanomaterials for radiotherapy have gained substantial attention. Key areas of focus include enhancing the efficacy of radiotherapy, achieving targeted drug delivery, minimizing adverse effects, and integrating nanomaterials with other therapeutic modalities. Future investigations are expected to improve the precision of radiotherapy, augment radiation effects, and optimize the tumor microenvironment. Full article
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30 pages, 2414 KiB  
Review
Melittin-Based Nanoparticles for Cancer Therapy: Mechanisms, Applications, and Future Perspectives
by Joe Rizkallah, Nicole Charbel, Abdallah Yassine, Amal El Masri, Chris Raffoul, Omar El Sardouk, Malak Ghezzawi, Therese Abou Nasr and Firas Kreidieh
Pharmaceutics 2025, 17(8), 1019; https://doi.org/10.3390/pharmaceutics17081019 - 6 Aug 2025
Viewed by 455
Abstract
Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt [...] Read more.
Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles, 2nd Edition)
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29 pages, 3455 KiB  
Review
Recent Advances in Nanoparticle and Nanocomposite-Based Photodynamic Therapy for Cervical Cancer: A Review
by Dorota Bartusik-Aebisher, Mohammad A. Saad, Agnieszka Przygórzewska and David Aebisher
Cancers 2025, 17(15), 2572; https://doi.org/10.3390/cancers17152572 - 4 Aug 2025
Viewed by 197
Abstract
Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in [...] Read more.
Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in the body, hypoxia in the tumor microenvironment, and limited light penetration. Recent advances in nanoparticle and nanocomposite platforms have addressed these challenges by integrating multiple functional components into a single delivery system. By encapsulating or conjugating photosensitizers in biodegradable matrices, such as mesoporous silica, organometallic structures and core–shell construct nanocarriers increase stability in water and extend circulation time, enabling both passive and active targeting through ligand decoration. Up-conversion and dual-wavelength responsive cores facilitate deep light conversion in tissues, while simultaneous delivery of hypoxia-modulating agents alleviates oxygen deprivation to sustain reactive oxygen species generation. Controllable “motor-cargo” constructs and surface modifications improve intratumoral diffusion, while aggregation-induced emission dyes and plasmonic elements support real-time imaging and quantitative monitoring of therapeutic response. Together, these multifunctional nanosystems have demonstrated potent cytotoxicity in vitro and significant tumor suppression in vivo in mouse models of cervical cancer. Combining targeted delivery, controlled release, hypoxia mitigation, and image guidance, engineered nanoparticles provide a versatile and powerful platform to overcome the current limitations of PDT and pave the way toward more effective, patient-specific treatments for cervical malignancies. Our review of the literature summarizes studies on nanoparticles and nanocomposites used in PDT monotherapy for cervical cancer, published between 2023 and July 2025. Full article
(This article belongs to the Section Cancer Therapy)
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21 pages, 6387 KiB  
Article
Carbon Dot-Enhanced Doxorubicin Liposomes: A Dual-Functional Nanoplatform for Cancer Therapy
by Corina-Lenuta Logigan, Cristian Peptu, Corneliu S. Stan, Gabriel Luta, Crina Elena Tiron, Mariana Pinteala, Aleksander Foryś, Bogdan Simionescu, Constanta Ibanescu, Adrian Tiron and Catalina A. Peptu
Int. J. Mol. Sci. 2025, 26(15), 7535; https://doi.org/10.3390/ijms26157535 - 4 Aug 2025
Viewed by 321
Abstract
Liposomes (LPs) represent one of the most effective nanoscale platforms for drug delivery in cancer therapy due to their favorable pharmacokinetic and various body tissue compatibility profiles. Building on recent findings showing that carbon dots derived from N-hydroxyphthalimide (CDs-NHF) possess intrinsic antitumor activity, [...] Read more.
Liposomes (LPs) represent one of the most effective nanoscale platforms for drug delivery in cancer therapy due to their favorable pharmacokinetic and various body tissue compatibility profiles. Building on recent findings showing that carbon dots derived from N-hydroxyphthalimide (CDs-NHF) possess intrinsic antitumor activity, herein, we investigate the possibility of preparing complex nano-platforms composed of LPs encapsulating CDs-NHF and/or doxorubicin (DOX) for breast and lung cancer. Various LP formulations were prepared and characterized using Cryo-TEM and Cryo-SEM for morphological analysis, while zeta potential and fluorescence assessments confirmed their stability and optical properties. Cellular effects were evaluated through immunofluorescence microscopy and proliferation assays. LPs-CDs-NHF significantly reduced cancer cell viability at lower concentrations compared to free CDs-NHF, and this effect was further amplified when combined with doxorubicin. Mechanistically, the liposomal formulations downregulated key signaling molecules including pAKT, pmTOR, and pERK, indicating the disruption of cancer-related pathways. These findings suggest that LPs containing CDs-NHF, either alone or in combination with DOX, exhibit synergistic antitumor activity and hold strong promise as multifunctional nanocarriers for future oncological applications. Full article
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23 pages, 5029 KiB  
Review
Synthesis and Biomedical Applications of PLA-HPG-Based Biodegradable Nanocarriers: A Review
by Yijun Shen, Xuehan He and Lei Chen
Biosensors 2025, 15(8), 502; https://doi.org/10.3390/bios15080502 - 3 Aug 2025
Viewed by 511
Abstract
The development of biodegradable nanocarriers has long been a priority for researchers and medical professionals in the realm of drug delivery. Because of their inherent benefits, which include superior biocompatibility, customizable degradability, easy surface functionalization, and stealth-like behavior, polylactic acid-hyperbranched polyglycerol (PLA-HPG) copolymers [...] Read more.
The development of biodegradable nanocarriers has long been a priority for researchers and medical professionals in the realm of drug delivery. Because of their inherent benefits, which include superior biocompatibility, customizable degradability, easy surface functionalization, and stealth-like behavior, polylactic acid-hyperbranched polyglycerol (PLA-HPG) copolymers have demonstrated a promising future in the field of biomedical research. The synthesis of PLA-HPG copolymers and the creation of their nanoparticles for biomedical uses have been the focus of current efforts. In this review, we summarize the synthetic strategies of PLA-HPG copolymers and corresponding nanoparticles, and highlight their physicochemical properties, biocompatibility, and degradation properties. Furthermore, we introduce a number of PLA-HPG nanoparticles that are utilized for surface skin delivery, wound dressing, and in vivo drug delivery biological applications. Finally, we conclude by offering our thoughts on how this nanoplatform might advance in the future. Full article
(This article belongs to the Special Issue State-of-the-Art Biosensors in China (2nd Edition))
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23 pages, 1912 KiB  
Review
Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer
by Keith N. Ncube, Iman van den Bout, Clarissa Willers, Chrisna Gouws and Werner Cordier
Int. J. Mol. Sci. 2025, 26(15), 7503; https://doi.org/10.3390/ijms26157503 - 3 Aug 2025
Viewed by 280
Abstract
Chemoresistance is a major challenge in the treatment of triple-negative breast cancer (TNBC). Multicellular spheroids are an attractive platform for investigating chemoresistance in TNBC, as they replicate the cues of the tumour microenvironment in vivo. We conducted a comprehensive literature search to summarise [...] Read more.
Chemoresistance is a major challenge in the treatment of triple-negative breast cancer (TNBC). Multicellular spheroids are an attractive platform for investigating chemoresistance in TNBC, as they replicate the cues of the tumour microenvironment in vivo. We conducted a comprehensive literature search to summarise the multifactorial and interlinked mechanisms driving chemoresistance in TNBC spheroids. These mechanisms include spatial heterogeneity, hypoxia, extracellular matrix remodelling, tumour–stroma crosstalk, drug efflux, apoptotic resistance, and cancer stem cell signalling. Strategies for overcoming chemoresistance in TNBC spheroids include nanocarrier systems to overcome spatial diffusion limitations, pathway inhibition, and targeting tumour–microenvironment interactions. Despite their advantages, some spheroid models face challenges such as low reproducibility, a lack of heterogeneity, variability in size and shape, limited vascularisation, and constraints in long-term culture. Advanced culturing platforms such as clinostat bioreactors allow for extended culture periods, enabling mature spheroid drug testing. Furthermore, advanced analytical techniques provide spatially resolved spheroid data. These multifactorial and interlinked mechanisms reflect the tumour microenvironment in vivo that spheroids recapitulate, rendering them valuable models for studying chemoresistance. The incorporation of stromal components and advanced analytical workflows will enhance the utility and translational relevance of spheroids as reliable preclinical models for drug discovery in TNBC. Full article
(This article belongs to the Special Issue Recent Advances in 3D Tumor Models for Cancer Research)
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