Praveen Kolimi, Sagar Narala, Ahmed Adel Ali Youssef, Dinesh Nyavanandi, Narendar Dudhipala
{"title":"A systemic review on development of mesoporous nanoparticles as a vehicle for transdermal drug delivery.","authors":"Praveen Kolimi, Sagar Narala, Ahmed Adel Ali Youssef, Dinesh Nyavanandi, Narendar Dudhipala","doi":"10.7150/ntno.77395","DOIUrl":"10.7150/ntno.77395","url":null,"abstract":"<p><p>Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) were developed in response to the need for materials with high thermal, chemical, and mechanical properties. The synthesis, ease of surface functionalization, tunable pore size, large surface area, and biocompatibility of MSNs make them useful in a variety of biomedical applications such as drug delivery, theranostics, and stem cell research. In addition, MSNs have a high capability of delivering actives ranging from small molecules such as drugs and amino acids to larger peptides, vaccines, and antibodies in general. Moreover, MSN-based transdermal delivery has sparked a lot of interest because of the increase in drug stability, permeation, and ease of functionalization. The functionalization of MSNs plays an important role in the efficient delivery of therapeutic agents in a highly controlled manner. This review introduced dermal and transdermal drug delivery systems, explained the anatomy of the skin, and summarized different barriers that affect the transdermal delivery of many therapeutic agents. In addition, the fundamentals of MSNs together with their physicochemical properties, synthesis approaches, raw materials used in their fabrication, and factors affecting their physicochemical properties will be covered. Moreover, the applications of MSNs in dermal and transdermal delivery, the biocompatibility of MSNs in terms of toxicity and safety, and biodistribution will be explained with the help of a detailed literature review. The review is covering the current and future perspectives of MSNs in the pharmaceutical field with therapeutic applications.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 1","pages":"70-89"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10009011","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}
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}
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":"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}
Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath
{"title":"Spatial analysis of nanoparticle distribution in human breast xenografts reveals nanoparticles targeted to cancer cells localized with tumor-associated stromal cells.","authors":"Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath","doi":"10.7150/ntno.84255","DOIUrl":"https://doi.org/10.7150/ntno.84255","url":null,"abstract":"<p><p>The biological influence of physicochemical parameters of \"targeted\" nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights. <b>Methods:</b> Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology analysis by comparing spatial distributions of nanoparticles (Prussian blue) with various stromal cells (CD31, SMA, F4/80, CD11c, etc.) and the target antigen-expressing (HER2) tumor cells. <b>Results:</b> Only BH nanoparticles were retained in tumors and generally concentrated in the tumor periphery, with nanoparticle content diminishing towards the tumor interior. Nanoparticle distribution correlated strongly with specific stromal cells within each tumor type, which varied among tumor types and between mouse strains. Weak or no correlation between nanoparticle distribution and HER2 positive cells, or CD31 cells was observed. <b>Conclusion:</b> Antibody-labeled nanoparticles were retained across all tumors, irrespective of presence of the \"target\" antigen. Though presence of antibody on nanoparticles correlated with retention, non-cancerous host stromal cells were responsible for their retention in the tumor microenvironment. This study highlights gaps in our understanding of the complex biological interplay between disease and host immune biology, and the need to account for the influence of underlying aberrant tumor biology as factors determining nanoparticle fate in vivo.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 4","pages":"393-411"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9897890","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}