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Keywords = hypoxia-targeting nanomedicine

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18 pages, 809 KiB  
Review
Nanomedicine-Enhanced Radiotherapy for Glioblastoma: Advances in Targeted Therapy and Adaptive Treatment Strategies
by Kamila Rawojć, Mansoor M. Ahmed, Ayesha Mukhtiar, Magdalena Łukowiak and Kamil Kisielewicz
Pharmaceutics 2025, 17(4), 508; https://doi.org/10.3390/pharmaceutics17040508 - 11 Apr 2025
Cited by 1 | Viewed by 1248
Abstract
Glioblastoma multiforme remains one of the most aggressive and treatment-resistant brain tumors that necessitate innovative therapeutic approaches. Nanomedicine has emerged as a promising strategy to enhance radiation therapy by improving drug delivery, radiosensitization, and real-time treatment monitoring. Stimuli-responsive nanoparticles can overcome limitations of [...] Read more.
Glioblastoma multiforme remains one of the most aggressive and treatment-resistant brain tumors that necessitate innovative therapeutic approaches. Nanomedicine has emerged as a promising strategy to enhance radiation therapy by improving drug delivery, radiosensitization, and real-time treatment monitoring. Stimuli-responsive nanoparticles can overcome limitations of the blood–brain barrier, modulate tumor microenvironment, and facilitate targeted therapeutic interventions. The integration of nanotechnology with proton and X-ray radiotherapy offers improved dose precision, enhanced radiosensitization, and adaptive treatment strategies. Furthermore, Artificial Intelligence-driven nanoparticle designs are optimizing therapeutic outcomes by tailoring formulations to tumor-specific characteristics. While promising, clinical translation remains a challenge that requires rigorous validation to ensure safety and efficacy. This review highlights advancements in nanomedicine-enhanced radiotherapy and future directions for glioblastoma multiforme treatment. Full article
(This article belongs to the Special Issue Smart Nanomedicine for Cancer Diagnosis and Therapy)
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54 pages, 7608 KiB  
Review
Development of Stimuli-Responsive Polymeric Nanomedicines in Hypoxic Tumors and Their Therapeutic Promise in Oral Cancer
by Jialong Hou, Zhijun Xue, Yao Chen, Jisen Li, Xin Yue, Ying Zhang, Jing Gao, Yonghong Hao and Jing Shen
Polymers 2025, 17(8), 1010; https://doi.org/10.3390/polym17081010 - 9 Apr 2025
Cited by 1 | Viewed by 1148
Abstract
Hypoxic tumors pose considerable obstacles to cancer treatment, as diminished oxygen levels can impair drug effectiveness and heighten therapeutic resistance. Oral cancer, a prevalent malignancy, encounters specific challenges owing to its intricate anatomical structure and the technical difficulties in achieving complete resection, thereby [...] Read more.
Hypoxic tumors pose considerable obstacles to cancer treatment, as diminished oxygen levels can impair drug effectiveness and heighten therapeutic resistance. Oral cancer, a prevalent malignancy, encounters specific challenges owing to its intricate anatomical structure and the technical difficulties in achieving complete resection, thereby often restricting treatment efficacy. The impact of hypoxia is particularly critical in influencing both the treatment response and prognosis of oral cancers. This article summarizes and examines the potential of polymer nanomedicines to address these challenges. By engineering nanomedicines that specifically react to the hypoxic tumor microenvironment, these pharmaceuticals can markedly enhance targeting precision and therapeutic effectiveness. Polymer nanomedicines enhance therapeutic efficacy while reducing side effects by hypoxia-targeted accumulation. The article emphasizes that these nanomedicines can overcome the drug resistance frequently observed in hypoxic tumors by improving the delivery and bioavailability of anticancer agents. Furthermore, this review elucidates the design and application of polymer nanomedicines for treating hypoxic tumors, highlighting their transformative potential in cancer therapy. Finally, this article gives an outlook on stimuli-responsive polymeric nanomedicines in the treatment of oral cancer. Full article
(This article belongs to the Special Issue Applications of Polymer Nanomaterials in Biomedicine)
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12 pages, 2711 KiB  
Article
ROS-Responsive Fluorinated Oxalate Nanomedicine for Dual Chemiluminescence/1⁹F MRI Imaging and Targeted Drug Release
by Anatoly Peshkov, Anel Urazaliyeva, Dariyana Saiduldinova, Kazbek Kulbergenov, Nasir Bala Alhassan, Almaz Beisenbayev, Yerkin Shabdan, Bauyrzhan Umbayev, Vsevolod Peshkov, Timur Sh. Atabaev, Timur Elebessov, Tri Thanh Pham and Chang-Keun Lim
Int. J. Mol. Sci. 2025, 26(7), 3304; https://doi.org/10.3390/ijms26073304 - 2 Apr 2025
Cited by 1 | Viewed by 735
Abstract
In this study, we developed a novel theranostic nanomedicine formulation that integrates multimodal imaging with controlled drug release in reactive oxygen species (ROS)-rich microenvironments. A fluorinated oxalate compound (FOC) was synthesized through a one-step condensation reaction between 1,1,1,3,3,3-hexafluoro-2-propanol and oxalyl chloride, characterized by [...] Read more.
In this study, we developed a novel theranostic nanomedicine formulation that integrates multimodal imaging with controlled drug release in reactive oxygen species (ROS)-rich microenvironments. A fluorinated oxalate compound (FOC) was synthesized through a one-step condensation reaction between 1,1,1,3,3,3-hexafluoro-2-propanol and oxalyl chloride, characterized by 1H, 13C, and 1⁹F NMR spectroscopy. The FOC and luminophore-incorporated nanomedicine formulations reacted rapidly with hydrogen peroxide via the peroxyoxalate chemiluminescence (POCL) mechanism, producing strong chemiluminescence and inducing a notable 19-fold increase in ratiometric 1⁹F NMR signal upon conversion to fluorinated alcohol (FAH), demonstrating promising potential for high-contrast 1⁹F MRI in deep tissue. Following ROS stimulation, the chemical conversion from hydrophobic FOC to hydrophilic FAH led to the degradation of the nanomedicines, facilitating payload release. In vitro experiments with A-431 cancer cells under hypoxic conditions confirmed ROS-responsive drug release, evidenced by enhanced fluorescence from model luminophores. Additionally, doxorubicin-loaded FOC nanomedicines reduced cell viability to 32% under hypoxia while remaining non-toxic in normoxic conditions. These results indicate that FOC-based nanomedicine formulations provide a promising platform for combined chemiluminescence and 1⁹F MRI with targeted therapeutic efficacy in ROS-rich inflammatory and cancerous tissues. Full article
(This article belongs to the Special Issue New Advances in Nanomedicine Innovation in Cancer Treatment)
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24 pages, 3171 KiB  
Review
Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance
by Wenjun Meng, Li Huang, Jiamin Guo, Qing Xin, Jiyan Liu and Yuzhu Hu
Pharmaceutics 2024, 16(12), 1549; https://doi.org/10.3390/pharmaceutics16121549 - 3 Dec 2024
Cited by 9 | Viewed by 2196
Abstract
Nanodrug delivery systems have revolutionized tumor therapy like never before. By overcoming the complexity of the tumor microenvironment (TME) and bypassing drug resistance mechanisms, nanotechnology has shown great potential to improve drug efficacy and reduce toxic side effects. This review examines the impact [...] Read more.
Nanodrug delivery systems have revolutionized tumor therapy like never before. By overcoming the complexity of the tumor microenvironment (TME) and bypassing drug resistance mechanisms, nanotechnology has shown great potential to improve drug efficacy and reduce toxic side effects. This review examines the impact of the TME on drug resistance and recent advances in nanomedicine delivery systems to overcome this challenge. Characteristics of the TME such as hypoxia, acidity, and high interstitial pressure significantly reduce the effectiveness of chemotherapy and radiotherapy, leading to increased drug resistance in tumor cells. Then, this review summarizes innovative nanocarrier designs for these microenvironmental features, including hypoxia-sensitive nanoparticles, pH-responsive carriers, and multifunctional nanosystems that enable targeted drug release and improved drug penetration and accumulation in tumors. By combining nanotechnology with therapeutic strategies, this review offers a novel perspective by focusing on the innovative design of nanocarriers that interact with the TME, a dimension often overlooked in similar reviews. We highlight the dual role of these nanocarriers in therapeutic delivery and TME modulation, emphasize their potential to overcome drug resistance, and look at future research directions. Full article
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35 pages, 3354 KiB  
Review
Oxidative Stress and Placental Pathogenesis: A Contemporary Overview of Potential Biomarkers and Emerging Therapeutics
by Ioana Vornic, Victor Buciu, Cristian George Furau, Pusa Nela Gaje, Raluca Amalia Ceausu, Cristina-Stefania Dumitru, Alina Cristina Barb, Dorin Novacescu, Alin Adrian Cumpanas, Silviu Constantin Latcu, Talida Georgiana Cut and Flavia Zara
Int. J. Mol. Sci. 2024, 25(22), 12195; https://doi.org/10.3390/ijms252212195 - 13 Nov 2024
Cited by 13 | Viewed by 4750
Abstract
Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS’s impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on [...] Read more.
Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS’s impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on OS in placental pathophysiology, examining its sources, mechanisms, and effects. While trophoblast invasion under low-oxygen conditions and hypoxia-induced OS regulate physiological placental development, excessive OS can lead to complications like miscarriage, preeclampsia, and intrauterine growth restriction. Promising OS biomarkers, including malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, show potential for the early detection of pregnancy complications. Therapeutic strategies targeting OS, such as mitochondria-targeted antioxidants, Nrf2 activators, and gasotransmitter therapies, demonstrate encouraging preclinical results. However, clinical translation remains challenging. Future research should focus on validating these biomarkers in large-scale studies and developing personalized therapies to modulate placental OS. Emerging approaches like extracellular vesicle-based therapies and nanomedicine warrant further investigation for both diagnostic and therapeutic applications in pregnancy-related complications. Integrating OS biomarkers with other molecular and cellular markers offers improved potential for the early identification of at-risk pregnancies. Full article
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30 pages, 2989 KiB  
Review
Metal Peroxide Nanoparticles for Modulating the Tumor Microenvironment: Current Status and Recent Prospects
by Jagadeesh Rajaram and Yaswanth Kuthati
Cancers 2024, 16(21), 3581; https://doi.org/10.3390/cancers16213581 - 24 Oct 2024
Cited by 3 | Viewed by 1888
Abstract
Background: The significant expansion of nanobiotechnology and nanomedicine has led to the development of innovative and effective techniques to combat various pathogens, demonstrating promising results with fewer adverse effects. Metal peroxide nanoparticles stand out among the crucial yet often overlooked types of nanomaterials, [...] Read more.
Background: The significant expansion of nanobiotechnology and nanomedicine has led to the development of innovative and effective techniques to combat various pathogens, demonstrating promising results with fewer adverse effects. Metal peroxide nanoparticles stand out among the crucial yet often overlooked types of nanomaterials, including metals. These nanoparticles are key in producing oxygen (O2) and hydrogen peroxide (H2O2) through simple chemical reactions, which are vital in treating various diseases. These compounds play a crucial role in boosting the effectiveness of different treatment methods and also possess unique properties due to the addition of metal ions. Methods: This review discusses and analyzes some of the most common metal peroxide nanoparticles, including copper peroxide (CuO2), calcium peroxide (CaO2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), barium peroxide (BaO2), and titanium peroxide (TiOx) nanosystems. These nanosystems, characterized by their greater potential and treatment efficiency, are primarily needed in nanomedicine to combat various harmful pathogens. Researchers have extensively studied the effects of these peroxides in various treatments, such as catalytic nanotherapeutics, photodynamic therapy, radiation therapy, and some combination therapies. The tumor microenvironment (TME) is particularly unique, making the impact of nanomedicine less effective or even null. The presence of high levels of reactive oxygen species (ROS), hypoxia, low pH, and high glutathione levels makes them competitive against nanomedicine. Controlling the TME is a promising approach to combating cancer. Results: Metal peroxides with low biodegradability, toxicity, and side effects could reduce their effectiveness in treating the TME. It is important to consider the distribution of metal peroxides to effectively target cancer cells while avoiding harm to nearby normal cells. As a result, modifying the surface of metal peroxides is a key strategy to enhance their delivery to the TME, thereby improving their therapeutic benefits. Conclusions: This review discussed the various aspects of the TME and the importance of modifying the surface of metal peroxides to enhance their therapeutic advantages against cancer, as well as address safety concerns. Additionally, this review covered the current challenges in translating basic research findings into clinical applications of therapies based on metal peroxide nanoparticles. Full article
(This article belongs to the Topic Nanomaterials and Diseases)
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30 pages, 2633 KiB  
Review
Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy
by Irina Negut and Bogdan Bita
Pharmaceutics 2024, 16(4), 463; https://doi.org/10.3390/pharmaceutics16040463 - 26 Mar 2024
Cited by 10 | Viewed by 2700
Abstract
This review addresses the urgent need for more targeted and less toxic cancer treatments by exploring the potential of multi-responsive polymersomes. These advanced nanocarriers are engineered to deliver drugs precisely to tumor sites by responding to specific stimuli such as pH, temperature, light, [...] Read more.
This review addresses the urgent need for more targeted and less toxic cancer treatments by exploring the potential of multi-responsive polymersomes. These advanced nanocarriers are engineered to deliver drugs precisely to tumor sites by responding to specific stimuli such as pH, temperature, light, hypoxia, and redox conditions, thereby minimizing the side effects associated with traditional chemotherapy. We discuss the design, synthesis, and recent applications of polymersomes, emphasizing their ability to improve therapeutic outcomes through controlled drug release and targeted delivery. Moreover, we highlight the critical areas for future research, including the optimization of polymersome–biological interactions and biocompatibility, to facilitate their clinical adoption. Multi-responsive polymersomes emerge as a promising development in nanomedicine, offering a pathway to safer and more effective cancer treatments. Full article
(This article belongs to the Special Issue Self-Assembled Amphiphilic Copolymers in Drug Delivery, 2nd Edition)
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49 pages, 4394 KiB  
Review
Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments
by Konstantinos Avgoustakis and Athina Angelopoulou
Pharmaceutics 2024, 16(2), 179; https://doi.org/10.3390/pharmaceutics16020179 - 26 Jan 2024
Cited by 7 | Viewed by 2823
Abstract
Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of [...] Read more.
Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of the tumor microenvironment (TME), in respect of effective drug accumulation and activity at the tumor site. The main focus is to overcome the obstacles of abnormal vasculature, dense stroma, extracellular matrix, hypoxia, and pH gradient acidosis. In this endeavor, nanomedicines that are targeting distinct features of TME have flourished; these aim to increase site specificity and achieve deep tumor penetration. Recently, research efforts have focused on the immune reprograming of TME in order to promote suppression of cancer stem cells and prevention of metastasis. Thereby, several nanomedicine therapeutics which have shown promise in preclinical studies have entered clinical trials or are already in clinical practice. Various novel strategies were employed in preclinical studies and clinical trials. Among them, nanomedicines based on biomaterials show great promise in improving the therapeutic efficacy, reducing side effects, and promoting synergistic activity for TME responsive targeting. In this review, we focused on the targeting mechanisms of nanomedicines in response to the microenvironment of solid tumors. We describe responsive nanomedicines which take advantage of biomaterials’ properties to exploit the features of TME or overcome the obstacles posed by TME. The development of such systems has significantly advanced the application of biomaterials in combinational therapies and in immunotherapies for improved anticancer effectiveness. Full article
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16 pages, 2865 KiB  
Article
Improving Tirapazamine (TPZ) to Target and Eradicate Hypoxia Tumors by Gold Nanoparticle Carriers
by Giimel Ajnai, Chun-Chia Cheng, Tzu-Chun Kan, Jeng-Wei Lu, Sri Rahayu, Amy Chiu and Jungshan Chang
Pharmaceutics 2022, 14(4), 847; https://doi.org/10.3390/pharmaceutics14040847 - 12 Apr 2022
Cited by 20 | Viewed by 3859
Abstract
Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we [...] Read more.
Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we successfully formulated and assessed the biochemical and therapeutic roles of the conjugated gold nanoparticles–Tirapazamine (GNPs–TPZ) on therapeutic assessments of MKN45-induced xenograft animal model. The results indicated that GNPs–TPZ was a potential nanomedicine for selectively targeting hypoxia tumors coupled with decreased side effects on healthy tissue or organs. TPZ significantly reduced cell viability of hypoxic gastric cancer MKN45 cells, but not in cells incubated in normoxia condition. For improving tumor targeting efficiency, furthermore, the GNPs drug carrier was conjugated to TPZ via biding mediator bovine serum albumin (BSA), and we demonstrated that this conjugated GNPs–TPZ retained the unique characteristics of hypoxic toxin and possessed the adequate feature of systemic bio-distributions in animals. GNPs–TPZ nanoparticles revealed their superior affinity to hypoxia tumors in the MKN45 xenograft. Moreover, GNPs–TPZ treatments did not significantly alter the biochemical parameters of blood samples acquired from animals. Taken together, TPZ, a prodrug activated by hypoxia, was conjugated with GNPs, whereas BSA severed as an excellent binding agent for preparing the conjugated GNPs–TPZ nanomedicines. We demonstrated that GNPs–TPZ enhanced tumor targeting, resulting in higher therapeutic efficacy compared to TPZ. We suggest that it may sever as an adjuvant treatment or combined therapy with other chemotherapeutics for the treatment of cancer patients in the future. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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21 pages, 1961 KiB  
Review
Recent Advances in Photodynamic Therapy for Deep-Seated Tumors with the Aid of Nanomedicine
by Wei-Peng Li, Chia-Jui Yen, Bo-Sheng Wu and Tak-Wah Wong
Biomedicines 2021, 9(1), 69; https://doi.org/10.3390/biomedicines9010069 - 12 Jan 2021
Cited by 55 | Viewed by 8596
Abstract
Photodynamic therapy (PDT) works through photoactivation of a specific photosensitizer (PS) in a tumor in the presence of oxygen. PDT is widely applied in oncology to treat various cancers as it has a minimally invasive procedure and high selectivity, does not interfere with [...] Read more.
Photodynamic therapy (PDT) works through photoactivation of a specific photosensitizer (PS) in a tumor in the presence of oxygen. PDT is widely applied in oncology to treat various cancers as it has a minimally invasive procedure and high selectivity, does not interfere with other treatments, and can be repeated as needed. A large amount of reactive oxygen species (ROS) and singlet oxygen is generated in a cancer cell during PDT, which destroys the tumor effectively. However, the efficacy of PDT in treating a deep-seated tumor is limited due to three main reasons: Limited light penetration depth, low oxygen concentration in the hypoxic core, and poor PS accumulation inside a tumor. Thus, PDT treatments are only approved for superficial and thin tumors. With the advancement of nanotechnology, PDT to treat deep-seated or thick tumors is becoming a reachable goal. In this review, we provide an update on the strategies for improving PDT with nanomedicine using different sophisticated-design nanoparticles, including two-photon excitation, X-ray activation, targeting tumor cells with surface modification, alteration of tumor cell metabolism pathways, release of therapeutic gases, improvement of tumor hypoxia, and stimulation of host immunity. We focus on the difficult-to-treat pancreatic cancer as a model to demonstrate the influence of advanced nanomedicine in PDT. A bright future of PDT application in the treatment of deep-seated tumors is expected. Full article
(This article belongs to the Special Issue Advanced Nanomedicines for Optical Imaging and Phototherapy)
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31 pages, 2150 KiB  
Review
Targeting Tumor Microenvironment for Cancer Therapy
by Catarina Roma-Rodrigues, Rita Mendes, Pedro V. Baptista and Alexandra R. Fernandes
Int. J. Mol. Sci. 2019, 20(4), 840; https://doi.org/10.3390/ijms20040840 - 15 Feb 2019
Cited by 959 | Viewed by 39098
Abstract
Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in [...] Read more.
Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing angiogenesis and, ultimately, resulting in metastasis. Exosomes secreted by TME cells are central players in all these events. The TME profile is preponderant on prognosis and impacts efficacy of anti-cancer therapies. Hence, a big effort has been made to develop new therapeutic strategies towards a more efficient targeting of TME. These efforts focus on: (i) therapeutic strategies targeting TME components, extending from conventional therapeutics, to combined therapies and nanomedicines; and (ii) the development of models that accurately resemble the TME for bench investigations, including tumor-tissue explants, “tumor on a chip” or multicellular tumor-spheroids. Full article
(This article belongs to the Special Issue Tumor Microenvironment 2019)
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