NanotheranosticsPub Date : 2024-05-28eCollection Date: 2024-01-01DOI: 10.7150/ntno.95251
Vaskuri G S Sainaga Jyothi, Nagavendra Kommineni
{"title":"Peptide Conjugated Boron Neutron Capture Therapy for Enhanced Tumor Targeting.","authors":"Vaskuri G S Sainaga Jyothi, Nagavendra Kommineni","doi":"10.7150/ntno.95251","DOIUrl":"10.7150/ntno.95251","url":null,"abstract":"<p><p>A cutting-edge non-invasive cancer treatment method called boron neutron capture therapy (BNCT) allows for the removal of cancerous tumor cells with the least possible damage to healthy tissue. It involves the exposure of cancer cells with low-energy thermal neutrons, boron-10 (<sup>10</sup>B) cellular uptake causes cancer cell death by producing alpha particles and recoiling lithium-7 (<sup>7</sup> Li) nuclei. Despite positive outcomes from clinical trials conducted all around the world, these substances have relatively limited tumor selectivity or low boron content per molecule. The development of new boron delivery agents with more selectivity and enhanced boron loading would advance this technique and promote its use in clinics as a primary cancer treatment. As peptide-binding cell surface receptors are typically overexpressed on cancer cells, they can be seen as interesting targets for targeted tumor therapy. The attachment of meta-carboranes to peptide conjugates that target tumor cells specifically by their overexpressed receptors may be a method to get around these problems. A state-of-the-art overview of current developments in the application of BNCT for cancer targeted therapy via peptide conjugation is the goal of this review.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 4","pages":"458-472"},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499230","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":"Multimodal evaluation of blood-brain barrier opening in mice in response to low-intensity ultrasound and a claudin-5 binder.","authors":"Liyu Chen, Jae Song, Gina Richter-Stretton, Wendy Lee, Pranesh Padmanabhan, Jürgen Götz","doi":"10.7150/ntno.95146","DOIUrl":"10.7150/ntno.95146","url":null,"abstract":"<p><p><b>Background:</b> The blood-brain barrier (BBB) is a major bottleneck in delivering therapeutics to the brain. Treatment strategies to transiently open this barrier include focused ultrasound combined with intravenously injected microbubbles (FUS<sup>+MB</sup>) and targeting of molecules that regulate BBB permeability. <b>Methods:</b> Here, we investigated BBB opening mediated by the claudin-5 binder cCPEm (a microorganismal toxin in a truncated form) and FUS<sup>+MB</sup> at a centre frequency of 1 MHz, assessing dextran uptake, broadband emission, and endogenous immunoglobulin G (IgG) extravasation. <b>Results:</b> FUS<sup>+MB</sup>-induced BBB opening was detectable at a pressure ≥0.35 MPa when assessed for leakage of 10 and 70 kDa dextran, and at ≥0.2 MPa for uptake of endogenous IgG. Treating mice with 20 mg/kg cCPEm failed to open the BBB, and pre-treatment with cCPEm followed by FUS<sup>+MB</sup> at 0.2 and 0.3 MPa did not overtly increase BBB opening compared to FUS<sup>+MB</sup> alone. Using passive cavitation detection (PCD), we found that broadband emission correlated with the peak negative pressure (PNP) and dextran leakage, indicating the possibility of using broadband emission for developing a feedback controller to monitor BBB opening. <b>Conclusions:</b> Together, our study highlights the challenges in developing combinatorial approaches to open the BBB and presents an additional IgG-based histological detection method for BBB opening.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 4","pages":"427-441"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499184","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":"Dual Functional Magnetic Nanoparticles Conjugated with Carbon Quantum Dots for Hyperthermia and Photodynamic Therapy for Cancer.","authors":"Mounika Choppadandi, Kondi Soumya, Sumanta Ghosh, Aishwarya Balu, Tanvi Shingote, Srivalliputtur Sarath Babu, Vani Sai Prasanna, Somasundaram Arumugam, Ravichandiran Velyutham, Murali M Yallapu, Govinda Kapusetti","doi":"10.7150/ntno.91871","DOIUrl":"10.7150/ntno.91871","url":null,"abstract":"<p><p>The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 4","pages":"442-457"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499183","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":"Targeted Nanotheransotics: Integration of Preclinical MRI and CT in the Molecular Imaging and Therapy of Advanced Diseases.","authors":"Jyoti Bonlawar, Aseem Setia, Ranadheer Reddy Challa, Bhaskar Vallamkonda, Abhishesh Kumar Mehata, Vaishali, Matte Kasi Viswanadh, Madaswamy S Muthu","doi":"10.7150/ntno.95791","DOIUrl":"10.7150/ntno.95791","url":null,"abstract":"<p><p>The integration of preclinical magnetic resonance imaging (MRI) and computed tomography (CT) methods has significantly enhanced the area of therapy and imaging of targeted nanomedicine. Nanotheranostics, which make use of nanoparticles, are a significant advancement in MRI and CT imaging. In addition to giving high-resolution anatomical features and functional information simultaneously, these multifunctional agents improve contrast when used. In addition to enabling early disease detection, precise localization, and personalised therapy monitoring, they also enable early disease detection. Fusion of MRI and CT enables precise in vivo tracking of drug-loaded nanoparticles. MRI, which provides real-time monitoring of nanoparticle distribution, accumulation, and release at the cellular and tissue levels, can be used to assess the efficacy of drug delivery systems. The precise localization of nanoparticles within the body is achievable through the use of CT imaging. This technique enhances the capabilities of MRI by providing high-resolution anatomical information. CT also allows for quantitative measurements of nanoparticle concentration, which is essential for evaluating the pharmacokinetics and biodistribution of nanomedicine. In this article, we emphasize the integration of preclinical MRI and CT into molecular imaging and therapy for advanced diseases.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 3","pages":"401-426"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946825","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}
NanotheranosticsPub Date : 2024-03-31eCollection Date: 2024-01-01DOI: 10.7150/ntno.87818
Pooja Suryavanshi, Dhananjay Bodas
{"title":"Knockout cancer by nano-delivered immunotherapy using perfusion-aided scaffold-based tumor-on-a-chip.","authors":"Pooja Suryavanshi, Dhananjay Bodas","doi":"10.7150/ntno.87818","DOIUrl":"10.7150/ntno.87818","url":null,"abstract":"<p><p>Cancer is a multifactorial disease produced by mutations in the oncogenes and tumor suppressor genes, which result in uncontrolled cell proliferation and resistance to cell death. Cancer progresses due to the escape of altered cells from immune monitoring, which is facilitated by the tumor's mutual interaction with its microenvironment. Understanding the mechanisms involved in immune surveillance evasion and the significance of the tumor microenvironment might thus aid in developing improved therapies. Although in vivo models are commonly utilized, they could be better for time, cost, and ethical concerns. As a result, it is critical to replicate an in vivo model and recreate the cellular and tissue-level functionalities. A 3D cell culture, which gives a 3D architecture similar to that found in vivo, is an appropriate model. Furthermore, numerous cell types can be cocultured, establishing cellular interactions between TME and tumor cells. Moreover, microfluidics perfusion can provide precision flow rates, thus simulating tissue/organ function. Immunotherapy can be used with the perfused 3D cell culture technique to help develop successful therapeutics. Immunotherapy employing nano delivery can target the spot and silence the responsible genes, ensuring treatment effectiveness while minimizing adverse effects. This study focuses on the importance of 3D cell culture in understanding the pathophysiology of 3D tumors and TME, the function of TME in drug resistance, tumor progression, and the development of advanced anticancer therapies for high-throughput drug screening.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 3","pages":"380-400"},"PeriodicalIF":0.0,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946284","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":"Herbal Theranostics: Controlled, Targeted Delivery and Imaging of Herbal Molecules.","authors":"Aseem Setia, Bhaskar Vallamkonda, Randheer Reddy Challa, Abhishesh Kumar Mehata, Paresh Badgujar, Madaswamy S Muthu","doi":"10.7150/ntno.94987","DOIUrl":"10.7150/ntno.94987","url":null,"abstract":"<p><p>Modern medicine relies on a small number of key biologics, which can be found in nature but require further characterization and purification before they can be used. Since the herbal remedy is given through a dated and ineffective method of drug administration, its effectiveness is diminished. The novel form of medicine delivery has the potential to increase the effectiveness of herbal substances while decreasing their side effects. This is the main idea behind utilising different ways of drug delivery in herbal treatments. Several benefits arise from novel formulations of herbal compounds as compared to their conventional counterparts. These include enhanced penetrating ability into tissues, constant delivery of effective doses, and resistance to physical and chemical degradation. Controlled and targeted delivery that include herbal components allow for more traditional dosing while simultaneously increasing their efficacy. Enhancing the biodistribution and target site accumulation of systemically administered herbal medicines is the goal of nanomedicine formulations. The field of nanotheranostics has made significant advancements in the development of herbal compounds by combining diagnostic and therapeutic functions on a single nanoscale platform. It is critically important to create a theranostic nanoplatform that is derived from plants and is intrinsically \"all-in-one\" for single molecules. In addition to examining the mechanistic approach to nanoparticle synthesis, this review highlights the therapeutic effects of nanoscale phytochemical delivery systems. Furthermore, we have evaluated the scope for future advancements in this field, discussed several nanoparticles that have been developed recently for herbal imaging, and provided experimental evidence that supports their usage.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 3","pages":"344-379"},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869873","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":"Characterizing morphological alterations in blood related disorders through Atomic Force Microscopy.","authors":"Rohini Rakshak, Shweta Bhatt, Sushant Sharma, Rutesh Agharkar, Santosh Bodakhe, Rohit Srivastava","doi":"10.7150/ntno.93206","DOIUrl":"10.7150/ntno.93206","url":null,"abstract":"<p><p>Atomic Force Microscopy (AFM) is a very flexible method that can create topographical images from a range of materials and image surfaces. Significantly, AFM has emerged as an invaluable tool for dissecting the morphology and biochemical aspects of body cells and tissues. The high-resolution imaging capabilities of AFM enable researchers to discern alterations in cell morphology and understand the underlying mechanisms of diseases. It contributes to understanding disease etiology and progression. In the context of this review, our focus will be directed towards elucidating the pivotal role of AFM in analysis of blood related disorders. Through detailed comparisons with normal cells, we delve into the alterations in size, shape, and surface characteristics induced by conditions such as cancer, diabetes, anaemia, and infections caused by pathogens. In essence, various work described in this article highlights to bridge the gap between traditional microscopy and in-depth analysis of blood-related pathologies, which in turn offers valuable perspectives for both research and clinical applications in the field.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 3","pages":"330-343"},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866729","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}
NanotheranosticsPub Date : 2024-03-09eCollection Date: 2024-01-01DOI: 10.7150/ntno.84995
Hadgu Mendefro Berehu, Srinivas Patnaik
{"title":"Biogenic Zinc Oxide Nanoparticles synthesized from <i>Tinospora Cordifolia</i> induce oxidative stress, mitochondrial damage and apoptosis in Colorectal Cancer.","authors":"Hadgu Mendefro Berehu, Srinivas Patnaik","doi":"10.7150/ntno.84995","DOIUrl":"10.7150/ntno.84995","url":null,"abstract":"<p><p>Cancer chemotherapy remains a serious challenge, and new approaches to therapy are urgently needed to build novel treatment regimens. The methanol extract of the stem of <i>Tinospora Cordifolia</i> was used to synthesize biogenic zinc oxide nanoparticles (ZnO-NPs) that display anticancer activities against colorectal cancer. Biogenic ZnO-NPs synthesized from methanol extract of <i>Tinospora Cordifolia</i> stem (ZnO-NPs TM) were tested against HCT-116 cell lines to assess anticancer activity. UV-Vis, FTIR, XRD, SEM, and TEM analysis characterized the biogenic ZnO-NPs. To see how well biogenic ZnO-NPs fight cancer, cytotoxicity, AO/EtBr staining, Annexin V/PI staining, mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS) analysis, and caspase cascade activity analysis were performed to assess the anticancer efficacy of biogenic ZnO-NPs. The IC50 values of biogenic ZnO-NPs treated cells (HCT-116 and Caco-2) were 31.419 ± 0.682μg/ml and 36.675 ± 0.916μg/ml, respectively. qRT-PCR analysis showed that cells treated with biogenic ZnO-NPs Bax and P53 mRNA levels increased significantly (<i>p</i> ≤ 0.001). It showed to have impaired MMP and increased ROS generation. In a corollary, our <i>in vivo</i> study showed that biogenic ZnO-NPs have an anti-tumour effect. Biogenic ZnO-NPs TM showed both <i>in vitro</i> and <i>in vivo</i> anticancer effects that could be employed as anticancer drugs.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 3","pages":"312-329"},"PeriodicalIF":0.0,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858687","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}
NanotheranosticsPub Date : 2024-03-09eCollection Date: 2024-01-01DOI: 10.7150/ntno.93064
Ilaria Zanolla, Martina Trentini, Elena Tiengo, Federica Zanotti, Tommaso Pusceddu, Andrea Rubini, Giuseppe Rubini, Francesca Brugnoli, Danilo Licastro, Marco Debortoli, Lucia Gemma Delogu, Letizia Ferroni, Luca Lovatti, Barbara Zavan
{"title":"Adipose-derived stem cell exosomes act as delivery vehicles of microRNAs in a dog model of chronic hepatitis.","authors":"Ilaria Zanolla, Martina Trentini, Elena Tiengo, Federica Zanotti, Tommaso Pusceddu, Andrea Rubini, Giuseppe Rubini, Francesca Brugnoli, Danilo Licastro, Marco Debortoli, Lucia Gemma Delogu, Letizia Ferroni, Luca Lovatti, Barbara Zavan","doi":"10.7150/ntno.93064","DOIUrl":"10.7150/ntno.93064","url":null,"abstract":"<p><p>Exosomes are nanosized extracellular vesicles secreted by all cell types, including canine adipose-derived stem cells (cADSCs). By mediating intercellular communication, exosomes modulate the biology of adjacent and distant cells by transferring their cargo. In the present work after isolation and characterization of exosomes derived from canine adipose tissue, we treated the same canine donors affected by hepatopathies with the previously isolated exosomes. We hypothesize that cADSC-sourced miRNAs are among the factors responsible for a regenerative and anti-inflammatory effect in the treatment of hepatopathies in dogs, providing the clinical veterinary field with an effective and innovative cell-free therapy. Exosomes were isolated and characterized for size, distribution, surface markers, and for their miRNomic cargo by microRNA sequencing. 295 dogs affected with hepatopathies were treated and followed up for 6 months to keep track of their biochemical marker levels. Results confirmed that exosomes derived from cADSCs exhibited an average diameter of 91 nm, and positivity to 8 known exosome markers. The administration of exosomes to dogs affected by liver-associated inflammatory pathologies resulted in the recovery of the animal alongside the normalization of biochemical parameters of kidney function. In conclusion, cADSCs-derived exosomes are a promising therapeutic tool for treating inflammatory disorders in animal companions.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 3","pages":"298-311"},"PeriodicalIF":0.0,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852052","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}
NanotheranosticsPub Date : 2024-03-09eCollection Date: 2024-01-01DOI: 10.7150/ntno.90516
Bin Qin, Xucai Chen, Jianhui Zhu, Jonathan Kopechek, Brandon Helfield, Francois Yu, Jissy Cyriac, Linda Lavery, Jennifer R Grandis, Flordeliza S Villanueva
{"title":"Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma.","authors":"Bin Qin, Xucai Chen, Jianhui Zhu, Jonathan Kopechek, Brandon Helfield, Francois Yu, Jissy Cyriac, Linda Lavery, Jennifer R Grandis, Flordeliza S Villanueva","doi":"10.7150/ntno.90516","DOIUrl":"10.7150/ntno.90516","url":null,"abstract":"<p><p><b>Rationale:</b> Microbubble (<b>MB</b>) contrast agents combined with ultrasound targeted microbubble cavitation (<b>UTMC</b>) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (<b>EGFR</b>), to squamous cell carcinoma (<b>SCC</b>) via a novel MB-liposome complex (<b>LPX</b>). <b>Methods: LPXs</b> were constructed by conjugation of cationic liposomes to the surface of C<sub>4</sub>F<sub>10</sub> gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (<b>SCC-VII-Luc</b>) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (<b>Luc siRNA</b>) were suspended. Ultrasound (<b>US</b>) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. <i>In vivo</i> siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×10<sup>8</sup> LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (<i>n</i>=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (<b>NC</b>) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment (\"sham\"). Tumor volume was serially measured by high-resolution 3D US imaging. <b>Results:</b> Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, <i>p</i><0.05) in SCC-VII-Luc cells at acoustic pressures 0.25 MPa to 0.9 MPa, while no significant silencing effect was seen at lower pressure (0.125 MPa). <i>In vivo,</i> EGFR siRNA LPX + UTMC reduced tumor EGFR expression by ~30% and significantly inhibited tumor growth by day 9 (~40% decrease in tumor volume vs. NC siRNA LPX + UTMC, <i>p</i><0.05). <b>Conclusions:</b> Luc siRNA LPXs + UTMC achieved functional delivery of Luc siRNA to SCC-VII-Luc cells <i>in vitro</i>. EGFR siRNA LPX + UTMC inhibited tumor growth and suppressed EGFR expression <i>in vivo</i>, suggesting that this platform holds promise for non-invasive, image-guided targeted delivery of therapeutic siRNA for cancer treatment.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"8 3","pages":"285-297"},"PeriodicalIF":0.0,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853971","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}