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38 pages, 2034 KB  
Review
The Application of Nanomaterials in Breast Cancer
by Kexin Guo, Yue Sun and Huihua Xiong
Pharmaceutics 2025, 17(12), 1608; https://doi.org/10.3390/pharmaceutics17121608 - 14 Dec 2025
Viewed by 341
Abstract
Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) [...] Read more.
Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) responsiveness of nanomaterials, there is tremendous potential for their applications in breast cancer diagnosis and therapy. In the diagnostic arena, nanomaterials serve as core components of novel contrast agents (e.g., gold nanorods, quantum dots, superparamagnetic iron oxide nanoparticles) and biosensing platforms, substantially enhancing the sensitivity and specificity of molecular imaging modalities—such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging (FLI)—and enabling high-sensitivity detection of circulating tumor cells and tumor-derived exosomes, among various liquid biopsy biomarkers. In therapy, nanoscale carriers (e.g., liposomes, polymeric micelles) improve tumor targeting and accumulation efficiency through passive and active targeting strategies, thereby augmenting anticancer efficacy while effectively reducing systemic toxicity. Furthermore, nanotechnology has spurred the rapid advancement of emerging modalities, including photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Notably, the construction of theranostic platforms that integrate diagnostic and therapeutic units within a single nanosystem enables in vivo, real-time visualization of drug delivery, treatment monitoring, and therapeutic response feedback, providing a powerful toolkit for advancing breast cancer toward personalized, precision medicine. Despite challenges that remain before clinical translation—such as biocompatibility, scalable manufacturing, and standardized evaluation—nanomaterials are undoubtedly reshaping the paradigm of breast cancer diagnosis and treatment. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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25 pages, 359 KB  
Review
The Gastrointestinal Tract: A Unique Battlefield for Bioengineering Delivery Platforms
by Teng Ma and Siyu Sun
Bioengineering 2025, 12(12), 1347; https://doi.org/10.3390/bioengineering12121347 - 10 Dec 2025
Viewed by 430
Abstract
Traditional drug delivery methods for gastrointestinal diseases, including oral and systemic administration, often suffer from degradation, inadequate mucosal absorption, and off-target toxicity. Consequently, these methods result in low bioavailability and suboptimal therapeutic outcomes for localized conditions such as inflammation and early-stage cancer. This [...] Read more.
Traditional drug delivery methods for gastrointestinal diseases, including oral and systemic administration, often suffer from degradation, inadequate mucosal absorption, and off-target toxicity. Consequently, these methods result in low bioavailability and suboptimal therapeutic outcomes for localized conditions such as inflammation and early-stage cancer. This review examines the innovative integration of advanced bioengineering platforms with therapeutic gastrointestinal endoscopy to address these delivery challenges. We concentrate on three principal bioengineered platforms: (1) nanoparticle systems (e.g., lipid, polymeric, and inorganic nanoparticles) designed for localized chemotherapy and theranostics; (2) in situ-forming hydrogels that serve as intelligent wound management materials and sustained drug depots; and (3) drug-eluting and biodegradable stents that convert passive luminal scaffolds into active, long-term drug-releasing devices. An analysis of these platforms demonstrates that their synergy with endoscopy facilitates precise, minimally invasive, and sustained local therapy, potentially transforming the treatment landscape for gastrointestinal diseases such as cancer and inflammatory bowel disease. Additionally, we investigate advanced strategies, including active targeting and stimulus-responsive release mechanisms, to enhance spatial precision. Despite promising preclinical advancements, clinical translation encounters challenges related to long-term biocompatibility, scalable manufacturing, regulatory pathways for drug-device combinations, and cost-effectiveness. Ultimately, the convergence of bioengineering and endoscopy presents significant potential to usher in a new era of precise, localized, and sustained micro-invasive treatments in gastroenterology. Full article
(This article belongs to the Special Issue Bioengineering Platforms for Drug Delivery)
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36 pages, 3847 KB  
Review
Lysosome as a Chemical Reactor
by Mahendiran Dharmasivam and Busra Kaya
Int. J. Mol. Sci. 2025, 26(23), 11581; https://doi.org/10.3390/ijms262311581 - 29 Nov 2025
Viewed by 784
Abstract
The lysosome is no longer viewed as a simple degradative “trash can” of the cell. The lysosome is not only degradative; its acidic, redox-active lumen also serves as a chemical “microreactor” that can modulate anticancer drug disposition and activation. This review examines how [...] Read more.
The lysosome is no longer viewed as a simple degradative “trash can” of the cell. The lysosome is not only degradative; its acidic, redox-active lumen also serves as a chemical “microreactor” that can modulate anticancer drug disposition and activation. This review examines how the distinctive chemical features of the lysosome, including its acidic pH (~4.5–5), strong redox gradients, limited thiol-reducing capacity, generation of reactive oxygen (ROS), diverse acid hydrolases, and reservoirs of metal ions, converge to influence the fate and activity of anticancer drugs. The acidic lumen promotes sequestration of weak-base drugs, which can reduce efficacy by trapping agents within a protective “safe house,” yet can also be harnessed for pH-responsive drug release. Lysosomal redox chemistry, driven by intralysosomal iron and copper, catalyzes Fenton-type ROS generation that contributes to oxidative damage and ferroptosis. The lysosome’s broad enzyme repertoire enables selective prodrug activation, such as through protease-cleavable linkers in antibody–drug conjugates, while its membrane transporters, particularly P-glycoprotein (Pgp), can sequester chemotherapies and promote multidrug resistance. Emerging therapeutic strategies exploit these processes by designing lysosomotropic drug conjugates, pH- and redox-sensitive delivery systems, and combinations that trigger lysosomal membrane permeabilization (LMP) to release trapped drugs. Acridine–thiosemicarbazone hybrids exemplify this approach by combining lysosomal accumulation with metal-based redox activity to overcome Pgp-mediated resistance. Advances in chemical biology, including fluorescent probes for pH, redox state, metals, and enzymes, are providing new insights into lysosomal function. Reframing the lysosome as a chemical reactor rather than a passive recycling compartment opens new opportunities to manipulate subcellular pharmacokinetics, improve drug targeting, and overcome therapeutic resistance in cancer. Overall, this review translates the chemical principles of the lysosome into design rules for next-generation, more selective anticancer strategies. Full article
(This article belongs to the Section Molecular Pharmacology)
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35 pages, 3954 KB  
Review
Modulating Cerebrospinal Fluid Composition in Neurodegenerative Processes: Modern Drug Delivery and Clearance Strategies
by Elizaveta A. Dutysheva, Anastasiya V. Zaerko, Mikita A. Valko, Ekaterina O. Antipina, Sergey M. Zimatkin, Boris A. Margulis, Irina V. Guzhova and Vladimir F. Lazarev
Int. J. Mol. Sci. 2025, 26(23), 11541; https://doi.org/10.3390/ijms262311541 - 28 Nov 2025
Viewed by 925
Abstract
Neurodegenerative diseases, traumatic brain injuries, and strokes are accompanied by the development of secondary damage—a long-term pathological cascade in which cerebrospinal fluid (CSF) plays a key role. Unlike primary damage, which is acute, secondary processes can progress over months and even years, creating [...] Read more.
Neurodegenerative diseases, traumatic brain injuries, and strokes are accompanied by the development of secondary damage—a long-term pathological cascade in which cerebrospinal fluid (CSF) plays a key role. Unlike primary damage, which is acute, secondary processes can progress over months and even years, creating a therapeutic window for neuroprotection. CSF acts not simply as a passive medium but as an active mediator of the spread of cytotoxic factors—reactive oxygen species, glutamate, proinflammatory cytokines, pathological protein aggregates (Aβ, α-synuclein, tau, etc.), and exosomes—which transport toxic molecules between brain regions. These processes are exacerbated by dysfunction of the blood-brain and blood–cerebrospinal fluid barriers, leading to the accumulation of damaging agents in the CSF and accelerated neurodegeneration. This review examines the molecular mechanisms of secondary injury, the role of barrier systems in maintaining CSF homeostasis, and current therapeutic strategies aimed at modulating CSF composition. Particular attention is paid to innovative approaches to drug delivery to the central nervous system—from bispecific antibodies and nanoparticles to invasive techniques such as immunoselective CSF aspiration and nanoporous implants. The potential of CSF as a source of diagnostic biomarkers and as a therapeutic target for personalized treatment of neurodegenerative conditions is highlighted. Full article
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42 pages, 2478 KB  
Review
Breast Cancer Progression and Its Theranostic Management via Folate-Directed Targeting of Glycoprotein Receptor
by Koyeli Girigoswami and Agnishwar Girigoswami
Med. Sci. 2025, 13(4), 275; https://doi.org/10.3390/medsci13040275 - 19 Nov 2025
Cited by 1 | Viewed by 863
Abstract
Breast cancer continues to rank among the most common and complex cancers worldwide. A promising approach is the direct delivery of drugs to cancer cells via specially designed nanocarriers that can target specific receptors on their surface, like folate receptors. When combined with [...] Read more.
Breast cancer continues to rank among the most common and complex cancers worldwide. A promising approach is the direct delivery of drugs to cancer cells via specially designed nanocarriers that can target specific receptors on their surface, like folate receptors. When combined with other therapies, these functionalized nanocarriers can increase the effectiveness of treatment by more precisely targeting cancer cells than traditional methods that rely on passive targeting. Folate receptors are glycoproteins with four isoforms, for which both laboratory and animal models have shown encouraging results in research. The numerous chemical methods for attaching folic acid (FA) and enhancing drug delivery in folic acid-modified nanocarriers for breast cancer are examined in this review. Additionally, it examines how these smart carriers combine chemotherapy with alternative therapies like photodynamic therapies and state-of-the-art theranostics. The review highlights how important it is to carry out comprehensive testing to ensure that these innovations can successfully move from the lab to real clinical settings, even though the potential is evident. Full article
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17 pages, 1269 KB  
Article
Targeted Analysis of Placental Steroid Hormones in Relation to Maternal Tobacco Smoke Exposure: Early Markers Relevant to DOHaD (Developmental Origins of Health and Disease)
by Alicja Kotłowska, Sebastian Fitzek, Rafał Stettner, Sylwia Narkowicz, Bogumiła Kiełbratowska and Piotr Szefer
Int. J. Mol. Sci. 2025, 26(21), 10548; https://doi.org/10.3390/ijms262110548 - 30 Oct 2025
Viewed by 539
Abstract
Maternal tobacco smoke exposure is associated with impaired fetal growth and long-term disease risk (DOHaD, Developmental Origins of Health and Disease). Whether placental steroid hormones are independently altered remains a matter of debate. We quantified six placental steroids (estradiol, estriol, estrone, progesterone, testosterone, [...] Read more.
Maternal tobacco smoke exposure is associated with impaired fetal growth and long-term disease risk (DOHaD, Developmental Origins of Health and Disease). Whether placental steroid hormones are independently altered remains a matter of debate. We quantified six placental steroids (estradiol, estriol, estrone, progesterone, testosterone, and pregnanediol) using HPLC–Corona CAD in 70 deliveries (C = 30; PS = 20; AS = 20). Distributional differences were assessed with Kruskal–Wallis and pairwise Mann–Whitney tests with Benjamini–Hochberg (BH) control. Adjusted associations used log-linear OLS with HC3 robust SE: Model A (gestational age, maternal BMI, newborn sex) and Model B (Model A + birth weight), reported as percent change vs. controls, computed as (exp(β) − 1) × 100 with 95% CI. Secondary analyses tested (i) multiclass logistic classification of C/PS/AS from the steroid panel (5-fold stratified CV) and (ii) prediction of birth weight (OLS and 2-component PLS). All six steroids differed by group (BH-adjusted p ranging from 9.18 × 10−12 to 6.66 × 10−8). In Model A, AS vs. C showed lower estrogens/progestins (estradiol, −46.2%; estriol, −24.7%; estrone, −25.9%; progesterone, −28.2%; pregnanediol, −31.4%) and higher testosterone (+40.8%); these effects persisted in Model B after adjusting for birth weight. The panel classified C/PS/AS with 0.900 cross-validated accuracy (weighted OvR AUC 0.994). Hormones poorly predicted birth weight (PLS CV R2 = −0.777). Maternal active and passive smoking is associated with a coherent and independent disruption of placental steroidogenesis. A targeted placental steroid panel offers biologically meaningful early markers relevant to DOHaD. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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24 pages, 2998 KB  
Article
Drug-Integrating Amphiphilic Nano-Assemblies: 3. PEG-PPS/Palmitate Nanomicelles for Sustained and Localized Delivery of Dexamethasone in Cell and Tissue Transplantations
by Giulio Palummieri, Saeida Saadat, Sung-Ting Chuang, Peter Buchwald and Diana Velluto
Pharmaceutics 2025, 17(10), 1337; https://doi.org/10.3390/pharmaceutics17101337 - 16 Oct 2025
Viewed by 1058
Abstract
Background: Glucocorticoids are an important class of therapeutics used in a variety of applications, including allotransplantations. Dexamethasone (Dexa) is well-known for its strong anti-inflammatory, immunosuppressive, and anticancer properties. However, its clinical use is often limited by its poor water solubility, poor pharmacokinetics, and [...] Read more.
Background: Glucocorticoids are an important class of therapeutics used in a variety of applications, including allotransplantations. Dexamethasone (Dexa) is well-known for its strong anti-inflammatory, immunosuppressive, and anticancer properties. However, its clinical use is often limited by its poor water solubility, poor pharmacokinetics, and high likelihood of systemic side effects. Methods: To address the issues, we tested a combined strategy where our original Drug-Integrating Amphiphilic Nano-Assemblies (DIANAs), a class of self-assembling polymeric nanoparticles designed for controlled drug release, were used to solubilize and deliver dexamethasone palmitate (DexP), a hydrophobic prodrug of dexamethasone. Results: The palmitate chains of the prodrug can form strong van der Waals interactions with the hydrophobic moieties of the PEG-PPS block copolymer used here. In water, this resulted in the self-assembling of stable dexamethasone palmitate–PEG–PPS nanomicelles, termed DexP-nMICs, with a 25 nm average diameter that slowly released Dexa over more than two weeks. Conclusions: Here we demonstrated that DexP-nMICs can carry elevated amounts of Dexa—increasing its solubility in water—prolong circulation in its pharmacologically active form in vivo and provide passive targeting to inflammation sites. The anti-inflammatory efficacy of DexP-nMICs was first confirmed in vitro on stimulated macrophages, demonstrating a significant reduction in cytokine secretion. An allogeneic mouse skin transplant model, used to assess the therapeutic potential of DexP-nMICs in vivo, confirmed its ability to provide graft-targeted delivery and prolong graft survival as compared to the unformulated parent drug. Therefore, DexP-nMICs are a promising candidate for sustained and localized use of anti-inflammatory drugs in cell and tissue transplantations. Full article
(This article belongs to the Special Issue Applications of Nanomaterials in Immunotherapies)
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21 pages, 5984 KB  
Article
Chrysin-Loaded Micelles Regulate Cell Cycle and Induce Intrinsic and Extrinsic Apoptosis in Ovarian Cancer Cells
by Serife Cakir, Ummugulsum Yildiz, Turgay Yildirim and Omer Aydin
Nanomaterials 2025, 15(17), 1362; https://doi.org/10.3390/nano15171362 - 4 Sep 2025
Cited by 2 | Viewed by 1239
Abstract
Effective intracellular delivery for ovarian cancer therapy remains a significant challenge. We present chrysin-loaded p(MMA-co-DMAEMA)-b-(OEGMA-co-DMA), PMOD-Chr, a nanoparticle platform precisely engineered via RAFT polymerization for advanced therapeutic delivery. This multi-functional platform features a hydrophobic p(MMA) core encapsulating chrysin (Chr), a pH-responsive p(DMAEMA) segment [...] Read more.
Effective intracellular delivery for ovarian cancer therapy remains a significant challenge. We present chrysin-loaded p(MMA-co-DMAEMA)-b-(OEGMA-co-DMA), PMOD-Chr, a nanoparticle platform precisely engineered via RAFT polymerization for advanced therapeutic delivery. This multi-functional platform features a hydrophobic p(MMA) core encapsulating chrysin (Chr), a pH-responsive p(DMAEMA) segment for endosomal escape, and a hydrophilic OEGMA (Oligo(ethylene glycol) methyl ether methacrylate) shell functionalized for enhanced cellular affinity and systemic stability. The combination of OEGMA and DMA (Dopamine methacrylamide) block facilitates passive targeting of ovarian cancer cells, enhancing internalization. Nanoparticles prepared via the nanoprecipitation method exhibited ~220 nm, demonstrating effective size modulation along with high homogeneity and spherical morphology. In A2780 and OVCAR3 ovarian cancer cells, PMOD-Chr demonstrated significantly enhanced cytotoxicity, substantially lowering the effective IC50 dose of Chr. Mechanistically, PMOD-Chr induced a potent G2/M cell cycle arrest, driven by the upregulation of the CDK1/Cyclin B1 complex. Furthermore, the formulation potently triggered programmed cell death by concurrently activating both the intrinsic apoptotic pathway, evidenced by the modulation of Bax, Bcl2, and caspase 9, and the extrinsic pathway involving caspase 8. These findings emphasize that precision engineering via RAFT polymerization enables the creation of sophisticated, multi-stage nanomedicines that effectively overcome key delivery barriers, offering a highly promising targeted strategy for ovarian cancer. Full article
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26 pages, 1208 KB  
Review
Doxorubicin Toxicity and Recent Approaches to Alleviating Its Adverse Effects with Focus on Oxidative Stress
by Lyubomira Radeva and Krassimira Yoncheva
Molecules 2025, 30(15), 3311; https://doi.org/10.3390/molecules30153311 - 7 Aug 2025
Cited by 3 | Viewed by 3448
Abstract
Despite the significant antitumor potential of doxorubicin and its widespread use in the treatment of various oncological diseases, its application is associated with side effects, among which the most common are cardiotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, and gonadotoxicity. In contemporary times, innovative strategies to [...] Read more.
Despite the significant antitumor potential of doxorubicin and its widespread use in the treatment of various oncological diseases, its application is associated with side effects, among which the most common are cardiotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, and gonadotoxicity. In contemporary times, innovative strategies to overcome the toxicity of doxorubicin and improve the effectiveness of therapies are intensively researched. The aim of this review is to discuss different approaches to alleviate the common toxic effects of doxorubicin, with an emphasis on oxidative stress. In particular, the review analyzes the significance of pharmaceutical nanotechnology for reducing doxorubicin toxicity while maintaining its antitumor effect (e.g., encapsulation of doxorubicin in passively and/or actively targeted nanoparticles to tumor tissue and cells). Other strategies commented in the review are the simultaneous delivery of doxorubicin with antioxidants and the administration of its derivatives with lower toxicity. Full article
(This article belongs to the Special Issue The Anticancer Drugs: A New Perspective)
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20 pages, 3766 KB  
Review
Challenges, Unmet Needs, and Future Directions for Nanocrystals in Dermal Drug Delivery
by Muzn Alkhaldi and Cornelia M. Keck
Molecules 2025, 30(15), 3308; https://doi.org/10.3390/molecules30153308 - 7 Aug 2025
Cited by 1 | Viewed by 2133
Abstract
Nanocrystals, defined as crystalline particles with dimensions in the nanometer range (<1000 nm), exhibit unique properties that enhance the efficacy of poorly soluble active compounds. This review explores the fundamental aspects of nanocrystals, including their characteristics and various preparation methods, while addressing critical [...] Read more.
Nanocrystals, defined as crystalline particles with dimensions in the nanometer range (<1000 nm), exhibit unique properties that enhance the efficacy of poorly soluble active compounds. This review explores the fundamental aspects of nanocrystals, including their characteristics and various preparation methods, while addressing critical factors that influence their stability and incorporation into final products. A key focus of the review is the advantages offered by nanocrystals in dermal applications. It also highlights their ability to enhance passive diffusion into the skin and facilitate penetration via particle-assisted dermal penetration. Additionally, the review discusses their capacity to penetrate into hair follicles, enabling targeted drug delivery, and their synergistic potential when combined with microneedles, which further enhance the dermal absorption of active compounds. The review also addresses several commercial products that successfully employ nanocrystal technology, showcasing its practical applications. Summary: Nanocrystals with their special properties are an emerging trend for dermal applications, particularly the development of plantCrystals—natural nanocrystals sourced from plant materials—which represent a promising path for future research and formulation strategies. These advancements could lead to more sustainable and effective dermal products. Full article
(This article belongs to the Section Natural Products Chemistry)
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29 pages, 3455 KB  
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
Cited by 1 | Viewed by 1499
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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26 pages, 1363 KB  
Review
From Structure to Function: The Promise of PAMAM Dendrimers in Biomedical Applications
by Said Alamos-Musre, Daniel Beltrán-Chacana, Juan Moyano, Valeria Márquez-Miranda, Yorley Duarte, Sebastián Miranda-Rojas, Yusser Olguín, Juan A. Fuentes, Danilo González-Nilo and María Carolina Otero
Pharmaceutics 2025, 17(7), 927; https://doi.org/10.3390/pharmaceutics17070927 - 18 Jul 2025
Cited by 7 | Viewed by 2798
Abstract
PAMAM dendrimers are distinguished by their capacity for functionalization, which enhances the properties of the compounds they transport, rendering them highly versatile nanoparticles with extensive applications in the biomedical domain, including drug, vaccine, and gene delivery. These dendrimers can be internalized into cells [...] Read more.
PAMAM dendrimers are distinguished by their capacity for functionalization, which enhances the properties of the compounds they transport, rendering them highly versatile nanoparticles with extensive applications in the biomedical domain, including drug, vaccine, and gene delivery. These dendrimers can be internalized into cells through various endocytic mechanisms, such as passive diffusion, clathrin-mediated endocytosis, and caveolae-mediated endocytosis, allowing them to traverse the cytoplasm and reach intracellular targets, such as the mitochondria or nucleus. Despite the significant challenge posed by the cytotoxicity of these nanoparticles, which is contingent upon the dendrimer size, surface charge, and generation, numerous strategies have been documented to modify the dendrimer surface using polyethylene glycol and other chemical groups to temporarily mitigate their cytotoxic effects. The potential of PAMAM dendrimers in cancer therapy and other biomedical applications is substantial, owing to their ability to enhance bioavailability, pharmacokinetics, and pharmacodynamics of active ingredients within the body. This underscores the necessity for further investigation into the optimization of internalization pathways and cytotoxicity of these nanoparticles. This review offers a comprehensive synthesis of the current literature on the diverse cellular internalization pathways of PAMAM dendrimers and their cargo molecules, emphasizing the mechanisms of entry, intracellular trafficking, and factors influencing these processes. Full article
(This article belongs to the Special Issue Biomedical Applications: Advances in Bioengineering and Drug Delivery)
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31 pages, 1683 KB  
Review
Strategic Advances in Targeted Delivery Carriers for Therapeutic Cancer Vaccines
by Junxi Wu, Jinghui Liang, Yuan Zhang, Chunyan Dong, Dejiang Tan, Hongyu Wang, Yiyang Zheng and Qing He
Int. J. Mol. Sci. 2025, 26(14), 6879; https://doi.org/10.3390/ijms26146879 - 17 Jul 2025
Cited by 1 | Viewed by 4113
Abstract
Cancer is one of the major global health burdens, and more effective treatments are needed. At present, there are surgery, targeted therapy, and immunotherapy for the treatment of tumors, but due to the limitations of diagnostic technology and drug resistance, surgery and targeted [...] Read more.
Cancer is one of the major global health burdens, and more effective treatments are needed. At present, there are surgery, targeted therapy, and immunotherapy for the treatment of tumors, but due to the limitations of diagnostic technology and drug resistance, surgery and targeted therapy have little effect. Active immunization in the field of immunotherapy can mobilize host immunity, trigger tumor-specific T-cell responses, and produce targeted cytotoxicity. Its efficacy largely depends on the targeted delivery efficiency of cancer vaccines. Although immunotherapy is more durable than other approaches, immunosuppression in the tumor microenvironment and immune evasion by malignant cells limit the therapeutic efficacy of cancer vaccines. To overcome these challenges, this review summarizes key strategies for improving vaccine vector targeting, as well as recent advances and trends in delivery systems. Full article
(This article belongs to the Special Issue Molecular Insights in Antivirals and Vaccines)
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59 pages, 2893 KB  
Review
Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI
by Shuai Fan, Wenyu Wang, Wenbo Che, Yicheng Xu, Chuan Jin, Lei Dong and Qin Xia
Metabolites 2025, 15(3), 201; https://doi.org/10.3390/metabo15030201 - 13 Mar 2025
Cited by 6 | Viewed by 4158
Abstract
Background: Tumor cells engage in continuous self-replication by utilizing a large number of resources and capabilities, typically within an aberrant metabolic regulatory network to meet their own demands. This metabolic dysregulation leads to the formation of the tumor microenvironment (TME) in most solid [...] Read more.
Background: Tumor cells engage in continuous self-replication by utilizing a large number of resources and capabilities, typically within an aberrant metabolic regulatory network to meet their own demands. This metabolic dysregulation leads to the formation of the tumor microenvironment (TME) in most solid tumors. Nanomedicines, due to their unique physicochemical properties, can achieve passive targeting in certain solid tumors through the enhanced permeability and retention (EPR) effect, or active targeting through deliberate design optimization, resulting in accumulation within the TME. The use of nanomedicines to target critical metabolic pathways in tumors holds significant promise. However, the design of nanomedicines requires the careful selection of relevant drugs and materials, taking into account multiple factors. The traditional trial-and-error process is relatively inefficient. Artificial intelligence (AI) can integrate big data to evaluate the accumulation and delivery efficiency of nanomedicines, thereby assisting in the design of nanodrugs. Methods: We have conducted a detailed review of key papers from databases, such as ScienceDirect, Scopus, Wiley, Web of Science, and PubMed, focusing on tumor metabolic reprogramming, the mechanisms of action of nanomedicines, the development of nanomedicines targeting tumor metabolism, and the application of AI in empowering nanomedicines. We have integrated the relevant content to present the current status of research on nanomedicines targeting tumor metabolism and potential future directions in this field. Results: Nanomedicines possess excellent TME targeting properties, which can be utilized to disrupt key metabolic pathways in tumor cells, including glycolysis, lipid metabolism, amino acid metabolism, and nucleotide metabolism. This disruption leads to the selective killing of tumor cells and disturbance of the TME. Extensive research has demonstrated that AI-driven methodologies have revolutionized nanomedicine development, while concurrently enabling the precise identification of critical molecular regulators involved in oncogenic metabolic reprogramming pathways, thereby catalyzing transformative innovations in targeted cancer therapeutics. Conclusions: The development of nanomedicines targeting tumor metabolic pathways holds great promise. Additionally, AI will accelerate the discovery of metabolism-related targets, empower the design and optimization of nanomedicines, and help minimize their toxicity, thereby providing a new paradigm for future nanomedicine development. Full article
(This article belongs to the Special Issue Drug Metabolism and New Drug Development for Cancers)
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23 pages, 2906 KB  
Article
The Legacy of COVID-19 in Breast Milk: The Association of Elevated Anti-Inflammatory and Antimicrobial Proteins with Vaccination or Infection
by Felicia Trofin, Petru Cianga, Daniela Constantinescu, Luminița Smaranda Iancu, Roxana Irina Iancu, Diana Păduraru, Eduard Vasile Nastase, Elena Roxana Buzilă, Cătălina Luncă, Corina Maria Cianga and Olivia Simona Dorneanu
Curr. Issues Mol. Biol. 2025, 47(3), 182; https://doi.org/10.3390/cimb47030182 - 11 Mar 2025
Cited by 1 | Viewed by 2053
Abstract
Background: Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. Materials [...] Read more.
Background: Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. Materials and Methods: Breast milk samples were collected from 50 breastfeeding mothers, including those who had either been vaccinated against SARS-CoV-2 or had recovered from the infection. These samples were compared with a control group consisting of 10 unvaccinated mothers with no history of COVID-19. Key antimicrobial and immune-regulatory proteins—lactoferrin, lactadherin, furin, tenascin C, granzyme B, and chitinase 3-like 1—were quantified using the Luminex multiplex analyzer. Results and Discussion: All targeted biomarkers were detected in breast milk, providing insights into the immune profile transferred to infants following COVID-19 infection or vaccination. These bioactive molecules highlight breastfeeding’s role in providing passive immunity and antimicrobial protection. The protein levels were found to be influenced by factors such as maternal inflammation, infant age, delivery mode, and parity, emphasizing the dynamic interaction between maternal immunity, lactation biology, and infant development. Conclusion: Breastfeeding serves as a powerful anti-SARS-CoV-2 defense mechanism, supported by the activity of lactoferrin, lactadherin, and furin, reinforcing its critical role in child health. Full article
(This article belongs to the Special Issue The Role of Bioactives in Inflammation)
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