Zoraida Andreu, Esther Masiá, David Charbonnier, María J Vicent
{"title":"A Rapid, Convergent Approach to the Identification of Exosome Inhibitors in Breast Cancer Models.","authors":"Zoraida Andreu, Esther Masiá, David Charbonnier, María J Vicent","doi":"10.7150/ntno.73606","DOIUrl":"https://doi.org/10.7150/ntno.73606","url":null,"abstract":"<p><p>Targeting cancer cell exosome release and biogenesis represents a potentially efficient means to treat tumors and prevent cancer recurrence/metastasis; however, the complexity and time-consuming nature of currently employed methods to purify and characterize exosomes represent obstacles to progression. Herein, we describe a rapid, convergent, and cost-efficient strategy to analyze candidate U.S. Food and Drug Administration (FDA)-approved drugs that inhibit exosome release and/or biogenesis using breast cancer cell line models in the hope of repurposing them for the clinical treatment of metastatic tumors. We combined the ExoScreen assay based on AlphaScreen<sup>TM</sup> technology with the antibody-mediated detection of an atypical lipid (lysobisphosphatidic acid - LBPA) present in the intra-luminal vesicle/exosomal fraction to achieve both extracellular and intracellular information on exosome modulation after treatment. As proof of concept for this strategy, we identified docetaxel, biscurcumin, primaquine, and doxorubicin as potential exosome release inhibitors in the Her-2 positive MDA-MB-453 and luminal A MCF7 cell lines. Dinaciclib also functioned as an exosome release inhibitor in MCF7 cells. Further, we explored the expression of proteins involved in exosome biogenesis (TSG101, CD9 tetraspanin, Alix, SMase2) and release (Rab11, Rab27) to decipher and validate the possible molecular mechanisms of action of the identified exosome inhibitors. We anticipate that our approach could help to create robust high-throughput screening methodologies to accelerate drug repurposing when using FDA-approved compound libraries and to develop rationally-designed single/combination therapies (including nanomedicines) that can target metastasis progression by modulating exosome biogenesis or release in various tumor types.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 1","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10691067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pre-clinical Investigations of Therapeutic Markers Associated with Acute and Chronic Restraint Stress: A Nuclear Magnetic Resonance Based Contrast Metabolic Approach.","authors":"Sanjay Singh, Sukanya Tripathy, Atul Rawat, Durgesh Dubey, Sarfraj Ahmad Siddiqui, Rajesh Ugale, Dinesh Kumar, Anand Prakash","doi":"10.7150/ntno.76294","DOIUrl":"https://doi.org/10.7150/ntno.76294","url":null,"abstract":"<p><p>Stress can be defined by two parameters, first the psychological sensing of pressure and second is the body's response. However, the exposure time to stress depicts the biological response produced against it. The effect of acute and chronic restraint stress on anxiety and the production of systemic metabolites were investigated in male Sprague-Dawley (SD) rats. Behavioural test was performed on elevated plus maze (EPM) in conjunction with the statistical analysis that exhibited the habituation during long term exposure to stress when compared with the short-term stress. These behaviour-based changes resulted in interpolated concentration of some serum metabolites like carbohydrates, amino acids and lipids as analysed by NMR. Metabolic analysis along with the multivariate analysis demonstrated that the expression of concentration of metabolites including glutamate, proline, succinate, citrate, and tyrosine is higher in the acute stress than the chronic stress, while glucose and lipids i.e., LDL and VLDL changed in the opposite trends. Thus, the aforesaid study provides an analytical strategy for the characterization of perturbed metabolites induced due to the behavioural modifications in an organism. It may further aid in developing potential therapeutic markers at the metabolic levels which may broaden the treatment options for stress and anxiety related disorders.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 1","pages":"91-101"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10691068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kritika Sood, Pranjali Yadav, Manu Jamwal, Reena Das, Asifkhan Shanavas
{"title":"Preclinical safety assessment of photoluminescent metal quantum clusters stabilized with autologous serum proteins for host specific theranostics.","authors":"Kritika Sood, Pranjali Yadav, Manu Jamwal, Reena Das, Asifkhan Shanavas","doi":"10.7150/ntno.82978","DOIUrl":"https://doi.org/10.7150/ntno.82978","url":null,"abstract":"<p><p>Host derived serum proteome stabilised red-emitting gold quantum clusters (or Au-QC-NanoSera or QCNS) of size range ~2 nm have been synthesised in a first reported study. The host serum was taken from bovine, murine and human origins to establish the proof of concept. <i>In-vitro</i> biocompatibility with normal murine L929 fibroblast cells and radiosensitisation ability against PLC/PRF/5 hepatoma cells was established. A concentration dependant radiosensitisation effect of QCNS at differential γ-radiation doses was observed with almost 90% killing of cancer cells at a radiation dose of 5Gy. Acute and subacute safety, and non-immunogenicity of autologously derived QCNS was established in in-bred C57BL/6 mice. The biodistribution analysis revealed that the QCNS were effectively cleared from the body over a course of 28 days and were found to pose no major threat to the proper functioning and morphology of the mice.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 3","pages":"316-326"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peelable Microneedle Patches Deliver Fibroblast Growth Factors to Repair Skin Photoaging Damage.","authors":"Guojun Yang, Shiqi Hu, Haiyue Jiang, Ke Cheng","doi":"10.7150/ntno.79187","DOIUrl":"https://doi.org/10.7150/ntno.79187","url":null,"abstract":"<p><p><b>Rationale:</b> UV light deeply penetrates the dermis, leading to inflammation and cell death with prolonged exposure. This is a major contributor to skin photoaging. In the pharmaceutical field, fibroblast growth factors (FGFs) have gained popularity for enhancing skin quality as they facilitate tissue remodeling and re-epithelization. Nonetheless, their effectiveness is significantly hindered by limited absorption. <b>Methods:</b> We have successfully created a dissolving microneedle (MN) patch that contains hyaluronic acid (HA) loaded with FGF-2 and FGF-21. This patch aims to improve the therapeutic efficiency of these growth factors while providing a simple administration method. We determined the performance of this patch in an animal model of skin photoaging. <b>Results:</b> The FGF-2/FGF-21-loaded MN (FGF-2/FGF-21 MN) patch demonstrated a consistent structure and suitable mechanical properties, allowing for easy insertion and penetration into mouse skin. Within 10 minutes of application, the patch released approximately 38.50 ± 13.38% of the loaded drug. Notably, the FGF-2/FGF-21 MNs exhibited significant improvements in UV-induced acute skin inflammation and reduced mouse skin wrinkles within a span of two weeks. Furthermore, the positive effects continued to enhance over a four-week treatment period. <b>Conclusion:</b> The proposed HA-based peelable MN patch provides an efficient approach for transdermal drug delivery, providing a promising method for improved therapeutic outcomes.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 4","pages":"380-392"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9811198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aziz Eftekhari, Carola Kryschi, David Pamies, Sukru Gulec, Elham Ahmadian, Dawid Janas, Soodabeh Davaran, Rovshan Khalilov
{"title":"Natural and synthetic nanovectors for cancer therapy.","authors":"Aziz Eftekhari, Carola Kryschi, David Pamies, Sukru Gulec, Elham Ahmadian, Dawid Janas, Soodabeh Davaran, Rovshan Khalilov","doi":"10.7150/ntno.77564","DOIUrl":"https://doi.org/10.7150/ntno.77564","url":null,"abstract":"<p><p>Nanomaterials have been extensively studied in cancer therapy as vectors that may improve drug delivery. Such vectors not only bring numerous advantages such as stability, biocompatibility, and cellular uptake but have also been shown to overcome some cancer-related resistances. Nanocarrier can deliver the drug more precisely to the specific organ while improving its pharmacokinetics, thereby avoiding secondary adverse effects on the not target tissue. Between these nanovectors, diverse material types can be discerned, such as liposomes, dendrimers, carbon nanostructures, nanoparticles, nanowires, etc., each of which offers different opportunities for cancer therapy. In this review, a broad spectrum of nanovectors is analyzed for application in multimodal cancer therapy and diagnostics in terms of mode of action and pharmacokinetics. Advantages and inconveniences of promising nanovectors, including gold nanostructures, SPIONs, semiconducting quantum dots, various nanostructures, phospholipid-based liposomes, dendrimers, polymeric micelles, extracellular and exome vesicles are summarized. The article is concluded with a future outlook on this promising field.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 3","pages":"236-257"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9331873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current status of Cancer Nanotheranostics: Emerging strategies for cancer management.","authors":"Vivek P Chavda, Avinash Khadela, Yasha Shah, Humzah Postwala, Pankti Balar, Lalit Vora","doi":"10.7150/ntno.82263","DOIUrl":"https://doi.org/10.7150/ntno.82263","url":null,"abstract":"<p><p>Cancer diagnosis and management have been a slow-evolving area in medical science. Conventional therapies have by far proved to have various limitations. Also, the concept of immunotherapy which was thought to revolutionize the management of cancer has presented its range of drawbacks. To overcome these limitations nanoparticulate-derived diagnostic and therapeutic strategies are emerging. These nanomaterials are to be explored as they serve as a prospect for cancer theranostics. Nanoparticles have a significant yet unclear role in screening as well as therapy of cancer. However, nanogels and Photodynamic therapy is one such approach to be developed in cancer theranostics. Photoactive cancer theranostics is a vivid area that might prove to help manage cancer. Also, the utilization of the quantum dots as a diagnostic tool and to selectively kill cancer cells, especially in CNS tumors. Additionally, the redox-sensitive micelles targeting the tumor microenvironment of the cancer are also an important theranostic tool. This review focuses on exploring various agents that are currently being studied or can further be studied as cancer theranostics.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 4","pages":"368-379"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mochamad Zakki Fahmi, Yu-Yu Aung, Musbahu Adam Ahmad, Alfinda Novi Kristanti, Satya Candra Wibawa Sakti, Oka Pradipta Arjasa, Hwei Voon Lee
{"title":"<i>In vivo</i> Study of Chalcone Loaded Carbon Dots for Enhancement of Anticancer and Bioimaging Potencies.","authors":"Mochamad Zakki Fahmi, Yu-Yu Aung, Musbahu Adam Ahmad, Alfinda Novi Kristanti, Satya Candra Wibawa Sakti, Oka Pradipta Arjasa, Hwei Voon Lee","doi":"10.7150/ntno.80030","DOIUrl":"https://doi.org/10.7150/ntno.80030","url":null,"abstract":"<p><p>The fluorescent imaging and drug delivery utilizing carbon dots nanomaterials (CDs) have attracted tremendously due to their unique optical ability and outstanding biocompatibility. Herein, we reported a new design of chalcone-loaded carbon dots (Chalcone-APBA-CDs) to serve chalcone transport onto cancer cells and enhance the CDs bioimaging and antitumor activity. The boronic acid was directly introduced to carbon dots (CDs) via pyrolysis process to drive CDs specifically to the cancer cell, and chalcone was mediated on CDs by ultrasonication to perform facile release of the drug delivery model. The successfully synthesized Chalcone-APBA-CDs were proved by their chemical structure, fluorescent activities, <i>in vitro</i> and <i>in vivo</i> analyses, and drug release systems using different pH. In addition, flow cytometry and confocal fluorescent imaging proved CDs' cellular uptake and imaging performance. <i>In vitro</i> analyses further proved that the Chalcone-APBA-CDs exhibited a higher toxicity value than bare CDs and efficiently inhibited the proliferation of the HeLa cells depending on their dose-response. Finally, the performance of Chalcone-APBA-CDs on cancer healing capability was examined <i>in vivo</i> with fibrosarcoma cancer-bearing mice, which showed a remarkable ability to reduce the tumor volume compared with saline (control). This result strongly suggested that the Chalcone-APBA-CDs appear promising simultaneously as cancer cell imaging and drug delivery.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 3","pages":"281-298"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9331870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Drug Encapsulated Lipid-Polymeric Nanohybrid as a Chemo-therapeutic Platform of Cancer.","authors":"Rahul Kumar, Vinish Ranjan Srivastava, Supratim Mahapatra, Daphika S Dkhar, Rohini Kumari, Kumari Prerna, Vikash Kumar Dubey, Pranjal Chandra","doi":"10.7150/ntno.81173","DOIUrl":"https://doi.org/10.7150/ntno.81173","url":null,"abstract":"<p><p>The focus of this research is to design a bioengineered drug delivery vehicle that is efficient in anti-cancer drug delivery in a controlled manner. The experimental work focuses on constructing a methotrexate-loaded nano lipid polymer system (MTX-NLPHS) that can transport methotrexate (MTX) in MCF-7 cell lines in a controlled manner through endocytosis via phosphatidylcholine. In this experiment, MTX is embedded with polylactic-co-glycolic acid (PLGA) in phosphatidylcholine, which acts as a liposomal framework for regulated drug delivery. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and dynamic light scattering (DLS) were utilized to characterize the developed nanohybrid system. The particle size and encapsulation efficiency of the MTX-NLPHS were found to be 198 ± 8.44 nm and 86.48 ± 0.31 %, respectively, which is suitable for biological applications. The polydispersity index (PDI) and zeta potential of the final system were found to be 0.134 ± 0.048 and -28 ± 3.50 mV, respectively. The lower value of PDI showed the homogenous nature of the particle size, whereas higher negative zeta potential prevented the system from agglomeration. An <i>in vitro</i> release kinetics was conducted to see the release pattern of the system, which took 250 h for 100% drug release This kind of system may carry the drug for a long time in the circulatory system and prevent the drug discharge. Other cell culture assays such as 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and reactive oxygen species (ROS) monitoring were used to see the effect of inducers on the cellular system. MTT assay showed cell toxicity of MTX-NLPHS reduced at the lower concentration of the MTX, however, toxicity increased at the higher concentration of the MTX as compared to free MTX. ROS monitoring c revealed more scavenging of ROS using MTX-NLPHS as compared to free MTX. Confocal microscopy suggested the MTX-NLPHS induced more nuclear elongation with cell shrinkage comparatively.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 2","pages":"167-175"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Narendar Dudhipala, Swetha Ettireddy, Ahmed Adel Ali Youssef, Goverdhan Puchchakayala
{"title":"Development and <i>In vivo</i> Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability.","authors":"Narendar Dudhipala, Swetha Ettireddy, Ahmed Adel Ali Youssef, Goverdhan Puchchakayala","doi":"10.7150/ntno.78102","DOIUrl":"https://doi.org/10.7150/ntno.78102","url":null,"abstract":"<p><p><b>Background:</b> Irbesartan (IR) is used in the treatment of hypertension, heart failure, and nephropathy in Type II diabetes. IR bioavailability is limited by poor solubility and presystemic metabolism. In our previous investigations, cyclodextrin (HPβCD) complexed solid lipid nanoparticles (SLNs) of IR were prepared, optimized, and characterized. The current study aimed to confirm the reproducibility of the previous methodology and to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of the selected lead formulations in an experimental animal model. <b>Methods:</b> SLNs were prepared by hot homogenization followed by probe sonication with IR/HPβCD inclusion complex loaded into a solid lipid (Dynasan 112). SLNs were evaluated for physical characteristics, drug content, entrapment efficiency, <i>in vitro</i> release profile, and surface morphology. The pharmacokinetic and pharmacodynamic behavior of the SLNs were evaluated in Wistar rats. <b>Results:</b> Photon correlation spectroscopy, drug content, entrapment efficiency, and dissolution studies results were reproducible and consistent with our earlier investigation. PK studies showed 2.1-, 6.6-, and 9.9-fold improvement in the relative oral bioavailability of the drug from IR-HPβCD, IR-SLN, and IR-HPβCD-SLN formulations, respectively compared to IR suspension. However, IR-HPβCD-SLNs showed 1.5- and 4.7-fold improvement in the relative oral bioavailability of the drug compared to IR-SLN and IR-HPβCD formulations, respectively. PD studies in hypertensive Wistar rats showed a good control over systolic blood pressure for 48 h for SLN formulations compared to 2 h for IR suspension. However, the IR-HPβCD inclusion complex exhibited immediate antihypertensive activity (0.5 h) with a period of systolic blood pressure control similar to IR suspension. <b>Conclusions:</b> The current approach exhibited improved oral bioavailability along with improved and prolonged pharmacodynamic effect.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 1","pages":"117-127"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10691063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}