International Journal of Nanomedicine最新文献

{"title":"Hyaluronic Acid-Modified and Doxorubicin-Loaded Au Nanorings for Dual-Responsive and Dual-Imaging Guided Targeted Synergistic Photothermal Chemotherapy Against Pancreatic Carcinoma.","authors":"Lingyu Hu, Zhengwei Song, Bin Wu, Xiaodan Yang, Fei Chen, Xiaoguang Wang","doi":"10.2147/IJN.S476936","DOIUrl":"https://doi.org/10.2147/IJN.S476936","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic carcinoma (PC) is a highly malignant digestive tumor. Nanotechnology-based minimally invasive techniques have been proposed to provide a new opportunity for PC treatment.</p><p><strong>Methods: </strong>A minimally invasive nanoplatform (named HA/DOX-AuNRs) is fabricated by HA modifying and DOX loading Au nanorings (AuNR). Because of their complicated geometric structure and tunable localized surface plasmon resonance peak in the second near-infrared laser window (NIR-II window), HA/DOX-AuNRs exhibit fluorescence/photoacoustic and photothermal properties, dual-responsive DOX release, and tumor-targeting ability. HA/DOX-AuNRs are expected to improve the tumor therapeutic efficiency and reduce undesirable side effects through fluorescence/photoacoustic dual-imaging guided targeted synergetic photothermal chemotherapy under NIR-II irradiation.</p><p><strong>Results: </strong>The morphological and physicochemical properties of HA/DOX-AuNRs are well-examined at first. The cytotoxicity, cellular uptake, and in vitro therapeutic effect of fluorescence/photoacoustic dual-imaging guided targeted synergetic photothermal chemotherapy are evaluated in Panc-1 cells. The in vivo biodistribution, anticancer effects, and systemic toxicity are investigated using PC xenograft models.</p><p><strong>Discussion: </strong>HA/DOX-AuNRs significantly improve the therapeutic efficacy in a dual-responsive and dual-imaging guided targeted synergy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13429-13442"},"PeriodicalIF":6.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of the Curcumin Analog CA7 Liposome and Its Evaluation for Efficacy Against Cervical Cancer in vitro and in vivo.","authors":"Linjin Xiong, Yumeng Wei, Hui Si, Zheng Li, Jie Wen, Furong Liu, Xiaodong Wang, Hongru Yang, Ligang Chen, Chao Pi, Yunwei Han, Ling Zhao","doi":"10.2147/IJN.S493074","DOIUrl":"https://doi.org/10.2147/IJN.S493074","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to develop liposomes (LP) containing a curcumin (CU) analog CA7 to enhance its pharmacokinetic profile and anti-cervical cancer (CC) effects.</p><p><strong>Methods: </strong>Single-factor and Box-Behnken experiments were conducted to optimize the formulation of CA7-loaded liposomes (CA7-LP). The in vitro release, stability, biocompatibility, and pharmacokinetic of CA7-LP were evaluated. The biological effects of CA7-LP on Hela cells were assessed using MTT assays, colony formation assays, wound healing assays, and flow cytometry. Additionally, the anti-CC efficacy of CA7-LP was tested in mouse models of transplanted tumors.</p><p><strong>Results: </strong>The optimal formulation of CA7-LP exhibited a particle size of 92.43 ± 1.52 nm, a polydispersity index of 0.27 ± 0.01, an encapsulation efficiency of 97.79 ± 1.49%, a drug loading of 3.23 ± 0.20%, and a zeta potential of -6.69 ± 0.77 mV. Transmission electron microscopy confirmed that a spherical morphology was exhibited by CA7-LP. The cumulative in vitro release of CA7-LP was found to be 2.84 times greater than that of CA7, and stability at room temperature was maintained for at least 90 d. Furthermore, a significantly higher uptake of CA7-LP by Hela cells was observed compared to curcumin and CA7, leading to enhanced inhibition of cell proliferation, migration and cell cycle, as well as increased apoptosis (<i>p</i> < 0.05). In vivo studies revealed that CA7-LP exhibited superior pharmacokinetic properties compared to CA7 (AUC: 3.58-fold, C_max: 5.65-fold, t_1/2z: 1.2-fold). The anti-CC effects of CA7-LP were found to be comparable to those of Cisplatin injection, with a better safety profile.</p><p><strong>Conclusion: </strong>The newly developed CA7-LP is considered a promising candidate for the treatment of CC, demonstrating high potential for clinical application.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13411-13428"},"PeriodicalIF":6.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physicochemical Property Effects on Immune Modulating Polymeric Nanoparticles: Potential Applications in Spinal Cord Injury.","authors":"Daniel J Kolpek, Jaechang Kim, Hisham Mohammed, John C Gensel, Jonghyuck Park","doi":"10.2147/IJN.S497859","DOIUrl":"https://doi.org/10.2147/IJN.S497859","url":null,"abstract":"<p><p>Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of the immune system. To achieve this, the review delves into the roles played by innate immune cells in SCI and investigates how various NP properties influence cellular interactions and subsequent immune modulation. Key NP properties such as size, surface charge, molecular weight, shape/morphology, surface functionalization, and polymer composition are thoroughly examined. Furthermore, the review establishes connections between these properties and their effects on the immunomodulatory functions of NPs. Ultimately, this review suggests that leveraging NPs and their physicochemical properties could serve as a promising therapeutic strategy for treating SCI and potentially other inflammatory diseases.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13357-13374"},"PeriodicalIF":6.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Antitumor Efficiency of <i>N⁴</i> -Tetradecyloxycarbonyl Gemcitabine-Loaded Liposomes for Pancreatic Cancer Chemotherapy.","authors":"Dan Wang, Xiaobo Wang, Yan Li, Xiaowei Wang, Xuelei Wang, Jiayi Su, Apeng Wang, Kai Lv, Mingliang Liu, Guimin Xia","doi":"10.2147/IJN.S485861","DOIUrl":"10.2147/IJN.S485861","url":null,"abstract":"<p><strong>Background: </strong>Gemcitabine (Gem) is one of the first-line chemotherapy drugs for pancreatic cancer treatment. However, its short half-life in plasma and adverse effects limited its broader application.</p><p><strong>Methods: </strong>A novel Gem derivative (<i>N⁴</i> -tetradecyloxycarbonyl gemcitabine, tcGem) was synthesized and encapsulated into liposomes (LipotcGem) to overcome the above shortcomings.</p><p><strong>Results: </strong>LipotcGem has been successfully formulated, with the average size of 115 nm, zeta potential values of -36 mV, encapsulation efficiency of up to 98%, and drug loading capacity of 8.1%. Compared to Gem, LipotcGem improved in vitro antitumor activity significantly, as evidenced by the lower IC₅₀, the higher percentage of apoptotic cells, the stronger ability to inhibit cell migration and invasion due to the higher cellular accumulation (100 times). Additionally, the endocytosis of LipotcGem was mainly mediated by caveolae, and was then processed in the lysosome, where tcGem was released and hydrolyzed into Gem. LipotcGem inhibited tumor growth by 70% in subcutaneous xenograft model and 90% in orthotopic xenograft model, respectively. LipotcGem suppressed tumor metastasis and prolonged survival without perceptible systemic toxicity, which may be caused by the longer t_1/2 in vivo (3.5 times, 5.23 <i>vs</i> 1.46 h) and more enrichment in tumor tissue (750 times).</p><p><strong>Conclusion: </strong>LipotcGem significantly increased the anti-tumor efficiency and decreased the toxicity for chemotherapy of pancreatic cancer.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13391-13410"},"PeriodicalIF":6.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Synthesis and Characterization of Silver Nanoparticles Using <i>Zingiber officinale</i> Extracts to Investigate Their Antibacterial Potential.","authors":"Muhammad Ramzan, Mai Abdel Haleem A Abusalah, Naveed Ahmed, Chan Yean Yean, Basit Zeshan","doi":"10.2147/IJN.S475656","DOIUrl":"10.2147/IJN.S475656","url":null,"abstract":"<p><strong>Background and purpose: </strong>Antimicrobial resistance (AMR) has emerged as a significant global concern. To combat this growing threat, various strategies have been employed, including the use of plant extracts and the biosynthesis of nanoparticles (NPs). The current study was designed to evaluate the phytochemical analysis of ginger (<i>Zingiber officinale</i>) extracts, characterize the silver nanoparticles (AgNPs) and to see their antibacterial potentials against multi-drug resistant (MDR) bacterial strains.</p><p><strong>Methods: </strong>The extracts were prepared and initially assessed for their phytochemical composition and antibacterial activity. Then, AgNPs were synthesized from these extracts at room temperature, and various analytical techniques, including UV-visible spectroscopy, X-ray diffraction (XRD), ATIR-FTIR, zeta sizer, scanning electron microscopy (SEM), and energy-dispersive X-ray analysis (EDXA), were used to characterize the NPs. After confirmation of prepared NPs, they were subjected to their antibacterial activity.</p><p><strong>Results: </strong>HPLC analysis demonstrated the presence of eight phytoconstituents in organic ginger extracts. The absorption spectra of the silver suspension exhibited surface plasmon resonance peaks with maxima between 420 and 448 nm. Functional groups like C-H, N-H, OH, C-O-C, C=O, and C-O were identified in both the organic and aqueous extracts of <i>Z. officinale</i>, playing a key role in the formation of AgNPs, as characterized by ATR-FTIR analysis. Both ginger organic and aqueous extract synthesized AgNPs crystalline structure was shown in XRD analysis and the particle size distribution showed average diameter of 200.5 nm of AgNPs from aqueous extracts. Scanning Electron Microscopy displayed spherical structure and EDA results showed the percentage of elements in synthesized AgNPs using plant extracts. Most promising antibacterial activity was obtained against <i>Escherichia coli ie</i> 20.83±0.53 for 100 µg/mL.</p><p><strong>Conclusion: </strong>The results of the current study showed that AgNPs synthesized from different ginger extracts have promising antibacterial properties and can be potential candidates for alternative treatment options for bacterial infections.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13319-13338"},"PeriodicalIF":6.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cs_xWO₃@NBs as a Multi-Image Guided Photothermal/Photodynamic Combination Therapy Platform for the Treatment of Hepatocellular Carcinoma.","authors":"Chunyue Wang, Xiaodong Wang, Yuhang Tian, Huimin Tian, Yichi Chen, Bolin Wu, Wen Cheng","doi":"10.2147/IJN.S484694","DOIUrl":"https://doi.org/10.2147/IJN.S484694","url":null,"abstract":"<p><strong>Purpose: </strong>Effective cancer treatment relies on the precise deployment of clinical imaging techniques to accurately treat tumors. One highly representative technology among these is multi-imaging guided phototherapy. This work introduces a new and innovative theranostic drug that combines near-infrared (NIR) irradiation-induced photodynamic therapy (PDT) and photothermal therapy (PTT) to treat malignancies. Moreover, it can be utilized as a contrasting substance for X-ray computed tomography (CT) imaging and contrast-enhanced ultrasound (CEUS) to aid in the administration of therapy.</p><p><strong>Methods: </strong>Cesium tungsten bronze nanobubbles (Cs_xWO₃@NBs) were constructed via a water-controlled solvothermal synthesis and thin film hydration of phospholipid. Various methods, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy, were used to analyze and describe the size, shape, and chemical characteristics of the nanoparticles. In this study, hepatoma cell lines HepG2 and HUH7 were employed in vitro, and xenotransplantation mouse models were used to assess their antitumor effects. A series of in vitro and in vivo trials were conducted to assess the effectiveness of combining photodynamic and photothermal therapies, as well as using CEUS and CT imaging.</p><p><strong>Results: </strong>The Cs_xWO₃@NBs exhibit photothermal effects and the generation of reactive oxygen species (ROS) under laser irradiation, thereby enabling effective photothermal and photodynamic combinatorial therapy. Following combined treatment, the activity and invasive capacity of hepatocellular carcinoma cells were markedly diminished, the development rate of the tumor was noticeably reduced, and the level of biological toxicity was low. Additionally, Cs_xWO₃@NBs possess the capacity to serve as both a CT imaging agent and a contrast-enhanced ultrasound agent.</p><p><strong>Conclusion: </strong>Cs_xWO₃@NBs represent a promising theranostic agent for image-guided cancer therapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13375-13389"},"PeriodicalIF":6.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stealth-Engineered Albumin-Coated Nanoparticles for Targeted Therapy: Effective Drug Delivery and Tumor Suppression in Xenograft-Zebrafish Model.","authors":"Sara Bozzer, Maria Cristina Grimaldi, Luca De Maso, Marcello Manfredi, Giuseppe Toffoli, Michele Dal Bo, Daniele Sblattero, Paolo Macor","doi":"10.2147/IJN.S476241","DOIUrl":"10.2147/IJN.S476241","url":null,"abstract":"<p><strong>Purpose: </strong>In the bloodstream, nanoparticles (NPs) interact with serum proteins to form the protein corona, which includes both opsonins, promoting NP recognition and elimination, and dysopsonins, which can inhibit opsonin activity. Albumin, the most abundant serum protein, is part of this corona and can act as a dysopsonin, potentially hiding NPs from the immune system. This study aims to investigate how a covalently bound layer of human serum albumin (HSA) on polymeric NPs affects the protein corona and their behavior in the immune system.</p><p><strong>Methods: </strong>We covalently attached HSA to the surface of polymeric NPs to modify the protein corona composition. These HSA-covered nanostructures were then decorated with an anti-CD19 recombinant antibody fragment to target malignant B cells, specifically acute lymphoblastic leukemia (ALL) cells. The safety profile and bioavailability of these targeted HSA-nanoparticles were evaluated in vitro and in vivo using a human-zebrafish xenograft model of ALL. The efficacy of the nanostructures in delivering encapsulated doxorubicin and suppressing tumor growth was also assessed.</p><p><strong>Results: </strong>The HSA coating on polymeric NPs effectively modified the protein corona, preventing opsonization and subsequent macrophage-mediated elimination. The targeted HSA-nanoparticles maintained a safe profile with reduced macrophage interaction and specifically targeted tumor cells in the xenograft model. This resulted in the successful delivery of doxorubicin, tumor growth suppression, and increased survival of the model organisms.</p><p><strong>Conclusion: </strong>The study demonstrates that HSA-coated nanoparticles can be used as a therapeutic nanoplatform with a safe profile and enhanced bioavailability. The ability to decorate these nanostructures with specific targeting agents, such as anti-CD19 antibodies, opens up the potential for developing versatile therapeutic platforms that can be tailored to target various clinical conditions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13267-13286"},"PeriodicalIF":6.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulus Responsive Nanocarrier for Enhanced Antitumor Responses Against Hepatocellular Carcinoma.","authors":"Deteng Zhang, Jinxiao Song, Zhenghui Jing, Huan Qin, You Wu, Jingyi Zhou, Xinlong Zang","doi":"10.2147/IJN.S486465","DOIUrl":"10.2147/IJN.S486465","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a serious global health concern, accounting for about 90% of all liver cancer instances. Surgical treatment is a fundamental aspect of HCC management; however, the challenge of postoperative recurrence significantly impacts mortality rates.</p><p><strong>Methods: </strong>We have developed a pH and reactive oxygen species (ROS) dual stimulus-responsive drug delivery system (PN@GPB-PEG NPs) loaded with chemotherapeutic paclitaxel (PTX) and indoleamine 2.3-dioxygenase (IDO) inhibitor NLG919, for HCC chemoimmunotherapy. The physiochemical properties, such as particle size, zeta potential, morphology, and encapsulation efficiency, were characterized. Furthermore, we investigated in vitro cytotoxicity, cellular uptake and immunogenic cell death in tumor cells treated with our nanoparticles. In vivo biodistribution, antitumor effects and immune responses were assessed in an HCC mice model.</p><p><strong>Results: </strong>PN@GPB-PEG NPs display pH-responsive properties with improved targeting abilities toward tumors and improved uptake by HCC cells. Upon exposure to oxygen peroxide (H₂O₂), the sophisticated design allows for rapid release of therapeutic agents. In this process, PTX induces immunogenic cell death (ICD), which activates the immune system to generate an antitumor response. Simultaneously, NLG919 works to inhibit IDO, mitigating the immunosuppressive environment. This combination strategy leverages the advantages of both chemotherapy and immunotherapy, resulting in a powerful synergistic antitumor effect. In a mouse model of HCC, our nanoparticles effectively inhibited the growth of primary and recurrent tumors.</p><p><strong>Conclusion: </strong>These encouraging results highlight the potential of our nanocarrier system as an innovative therapeutic approach to address HCC primary tumor and postsurgical recurrence, providing hope for enhanced patient outcomes.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13339-13355"},"PeriodicalIF":6.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfiram-Loaded Nanoparticles Inhibit Long-Term Proliferation on Preadipocytes.","authors":"Helen Yarimet Lorenzo-Anota, José María Gómez-Cantú, Eduardo Vázquez-Garza, Judith Bernal-Ramirez, Héctor Chapoy-Villanueva, Karla Mayolo-Deloisa, Jorge Benavides, Marco Rito-Palomares, Omar Lozano","doi":"10.2147/IJN.S467909","DOIUrl":"10.2147/IJN.S467909","url":null,"abstract":"<p><strong>Introduction: </strong>Disulfiram (DSF) reduces insulin resistance and weight gain in obese mice. However, the effect on adipose tissue is unexplored due to their high instability under physiological conditions, limiting clinical applications. Thus, it is meaningful to develop a DSF carrier for sustained release to adipose tissue. We optimized the synthesis of poly-ε-caprolactone (PCL) nanoparticles (NPs) loaded with DSF and analyzed their effect on adipose tissue cells in vitro.</p><p><strong>Methods: </strong>The NPs were synthesized by nanoprecipitation method, varying its solvent, either acetone or acetone/dichloromethane (60:40) (v/v), and ratio PCL:DSF (w/w) 1:2, 1:1, 2:1 and, 1:0; finding the best condition was obtained with acetone/dichloromethane solvent mixture and 2:1 PCL:DSF. Then, NPs toxicity was analyzed on adipose cells (preadipocytes, white-like adipocytes, and macrophages) assessing association and internalization, cell viability, and cell death mechanism.</p><p><strong>Results: </strong>NPs were spherical with a particle size distribution of 203.2 ± 29.33 nm, a ζ-potential of -20.7 ± 4.58 mV, a PDI of 0.296 ± 0.084, and a physical drug loading of 18.6 ± 5.80%. Sustained release was observed from 0.5 h (10.94 ± 2.38%) up to 96 h (91.20 ± 6.03%) under physiological conditions. NPs internalize into macrophages, white-like adipocytes and preadipocytes without modifying cell viability on white-like adipocytes and macrophages. Preadipocytes reduce cell viability, inducing mitochondrial damage, increased mitochondrial reactive oxygen species production and loss of mitochondrial membrane potential, leading to effector caspases 3/7 cleaved, resulting in apoptosis. Finally, long-term proliferation inhibition was observed, highlighting the bioequivalent effect of PCL-DSF NPs compared to free DSF.</p><p><strong>Conclusion: </strong>Our data demonstrated the biological interaction of PCL NPs with adipose cells in vitro. The selective cytotoxicity of DSF towards preadipocytes resulted in milder effects when it was delivered nanoencapsulated compared to the free drug. These results suggest promising pharmacological alternatives for DSF long-term delivery on adipose tissue.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13301-13318"},"PeriodicalIF":6.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eugenol Nanoparticles Ameliorate Doxorubicin-Induced Spermatogenic Dysfunction by Inhibiting the PINK1/Parkin and BNIP3/NIX Signaling Pathways.","authors":"Yang Fu, Peipei Yuan, Manyv Wang, Yajuan Zheng, Yan Zhang, Lirui Zhao, Qingyun Ma, Pengsheng Wang, Xiaotian Sun, Xiaoke Zheng, Weisheng Feng","doi":"10.2147/IJN.S494056","DOIUrl":"10.2147/IJN.S494056","url":null,"abstract":"<p><strong>Purpose: </strong>Doxorubicin (DOX) precipitates cell apoptosis in testicular tissues, and it is imperative to develop drugs to alleviate the spermatogenic disorders it causes. <i>Eugenia caryophyllata</i> Thunb is often used to treat male sexual disorders. Eugenol, a major component of <i>Eugenia caryophyllata</i> Thunb. has inadequate stability and low solubility, which limits its pharmacological effects. Eugenol nanoparticles (NPs) (ENPs) are expected to overcome these limitations. The protective effects of ENPs against DOX-induced reproductive toxicity were studied in mice.</p><p><strong>Methods: </strong>Eugenol was encapsulated in Methoxy-Poly(ethylene glycol)-Poly(lactide-co-glycolide) nanoparticles (mPEG-PLGA-NPs), and their role in ameliorating spermatogenic dysfunction was verified in vivo and in vitro.</p><p><strong>Results: </strong>We present a promising delivery system that encapsulates eugenol into mPEG-PLGA-NPs and forms them into nanocomposites. In vitro, ENPs significantly reduced doxorubicin-induced ROS and inflammatory factors in GC-1 cells and regulated the expression of the mitochondrial autophagy protein PINK1 and meiosis-related protein SCP3. In vivo, ENPs significantly increased sperm motility in mice, reduced apoptosis and oxidative stress in the testes, inhibited the testicular PINK1/Parkin and BNIP3/NIX signaling pathways, and enhanced the expression of factors associated with meiosis.</p><p><strong>Conclusion: </strong>Given their safety and efficacy, these ENPs have potential application prospects in mitigating doxorubicin-induced spermatogenic dysfunction.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"13287-13300"},"PeriodicalIF":6.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}