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Herein, we innovatively propose a mucin 1 and azoreductase dual-responsive DNA tetrahedral nanoprobe for two-step lighting imaging-guided photodynamic therapy of tumors. We hope that this highly specific, responsive and well biocompatible drug delivery system can be effectively used for the performance of cancer therapy in the hypoxia-related biomedical field.

Fluorescence molecular probes have been regarded as a valuable tool for RNA detection and imaging. However, the pivotal challenge is how to develop an efficient fluorescence imaging platform for accurate identification of RNA molecules with low expression in complicated physiological environments. Herein, we construct the DNA nanoparticles to glutathione (GSH)-responsive controllable release of hairpin reactants for catalytic hairpin assembly (CHA)-hybridization chain reaction (HCR) cascade circuits, which enables the analysis and imaging of low-abundance target mRNA in living cells. The aptamer-tethered DNA nanoparticles are constructed via the self-assembly of single-stranded DNAs (ssDNAs), exhibiting sufficient stability, cell-specific penetration, and precise controllability. Moreover, the in-depth integration of different DNA cascade circuits shows the improved sensing performance of DNA nanoparticles in live cell analysis. Therefore, through the combination of multi-amplifiers and programmable DNA nanostructure, the developed strategy enables accurately triggered release of hairpin reactants and further achieves sensitive imaging and quantitative evaluation of survivin mRNA in carcinoma cells, which provides a potential platform to facilitate RNA fluorescence imaging applications in early clinical cancer theranostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Effectively delivering therapeutics for treating brain tumors is hindered by the physical and biological barriers in the brain. Even with the compromised blood-brain barrier and highly angiogenic blood-tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial-based formulations, hardly reach intracranial tumors. This work investigates sub-5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7-ethyl-10-hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface-to-volume ratio, uIONP shows one- or three-folds higher SN38 loading efficiency (48.3 ± 6.1%, mg/mg Fe) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with <10% over 48 h at pH 7.4, but 86% at pH 5, thus being protected from converting to inactive glucuronide by UDP-glucuronosyltransferase 1A1. Conjugating α v β 3 -integrin-targeted cyclo(Arg-Gly-Asp-D-Phe-Cys) (RGD) as ligands, RGD-uIONP/SN38 demonstrates targeted cytotoxicity to α v β 3 -integrin-overexpressed U87MG GBM cells with a half-maximal inhibitory concentration (IC 50 ) of 30.9 ± 2.2 nm. The efficacy study using an orthotopic mouse model of GBM reveals tumor-specific delivery of 11.5% injected RGD-uIONP/SN38 (10 mg Fe kg -1 ), significantly prolonging the survival in mice by 41%, comparing to those treated with SN38 alone (p < 0.001)., (© 2022 Wiley-VCH GmbH.)

Pancreatic cancer remains one of the most lethal cancers largely due to the inefficient delivery of therapeutics. Nanomaterials have been extensively investigated as drug delivery platforms, showing improved drug pharmacodynamics and pharmacokinetics. However, their applications in pancreatic cancer have not yet been successful due to limited tumor delivery caused by dense tumor stroma and distorted tumor vasculatures. Meanwhile, smaller-sized nanomaterials have shown improved tumor delivery and retention in various tumors, including pancreatic tumors, suggesting their potential in enhancing drug delivery. An ultrafine iron oxide nanoparticle (uIONP) was used to encapsulate 7-ethyl-10-hydroxyl camptothecin (SN38), the water-insoluble active metabolite of pancreatic cancer chemotherapy drug irinotecan. Insulin-like growth factor 1 (IGF-1) was conjugated to uIONP as a ligand for targeting pancreatic cancer cells overexpressing IGF-1 receptor (IGF1R). The SN38 loading and release profile were characterized. The pancreatic cancer cell targeting using IGF1-uIONP/SN38 and subsequently induced cell apoptosis were also investigated. IGF1-uIONP/SN38 demonstrated a stable drug loading in physiological pH with the loading efficiency of 68.2 ± 3.5% (SN38/Fe, wt%) and < 7% release for 24 h. In tumor-interstitial- and lysosomal-mimicking pH (6.5 and 5.5), 52.2 and 91.3% of encapsulated SN38 were released over 24 h. The IGF1-uIONP/SN38 exhibited specific receptor-mediated cell targeting and cytotoxicity Ato MiaPaCa-2 and Panc02 pancreatic cancer cells with IC50 of 11.8 ± 2.3 and 20.8 ± 3.5 nM, respectively, but not to HEK293 human embryonic kidney cells. IGF1-uIONP significantly improved the targeted SN38 delivery to pancreatic cancer cells, holding the potential for in vivo theranostic applications., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The rapid development and advances in nanomaterials and nanotechnology in the past two decades have made profound impact in our approaches to individualized disease diagnosis and treatment. Nanomaterials, mostly in the range of 10-200 nm, developed for biomedical applications provide a wide range of platforms for building and engineering functionalized structures, devices, or systems to fulfill the specific diagnostic and therapeutic needs. Driven by achieving the ultimate goal of clinical translation, sub-5 nm nano-constructs, in particular inorganic nanoparticles such as gold, silver, silica, and iron oxide nanoparticles, have been developed in recent years to improve the biocompatibility, delivery and pharmacokinetics of imaging probes and drug delivery systems, as well as in vivo theranostic applications. The emerging studies have provided new findings that demonstrated the unique size-dependent physical properties, physiological behaviors and biological functions of the nanomaterials in the range of the sub-5 nm scale, including renal clearance, novel imaging contrast, and tissue distribution. This advanced review attempts to introduce the new strategies of rational design for engineering nanoparticles with the core sizes under 5 nm in consideration of the clinical and translational requirements. We will provide readers the update on recent discoveries of chemical, physical, and biological properties of some biocompatible sub-5 nm nanomaterials as well as their demonstrated imaging and theranostic applications, followed by sharing our perspectives on the future development of this class of nanomaterials. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants., (© 2020 Wiley Periodicals LLC.)

Background: Nanoparticle-based drug delivery systems hold great promise for the treatment of major diseases. However, their slow translation from bench to the clinic posts a concern. It is mainly attributed to the lack of suitable in vitro platforms for rapid and accurate screening of nanomedicine. Recent developments in microfluidic technologies have provided the possibility to reproduce the biomimetic blood vessel microenvironments outside the body, thus offering a convenient means to characterize the in vivo dynamics and biological responses of nanoparticles during circulation., Objective: In this review, we discuss the challenges facing the field of nanoparticle drug delivery and highlight the urgent need for construction of blood-vessel-on-a-chip platforms for testing nanomedicine. We subsequently illustrate advances in fabricating various well-controlled blood-vessel-on-a-chip platforms, covering a few examples that have used such models for evaluating nanoparticle behaviors. We then summarize with conclusions and perspectives., Conclusion: We anticipate that, further development of these blood-vessel-on-a-chip platforms with improved biomimetic parameters, tissue specificity, and personalization, will enable their wide applications in drug screening including nanomedicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The rapid development and advances in nanomaterials and nanotechnology in the past two decades have made profound impact in our approaches to individualized disease diagnosis and treatment. Nanomaterials, mostly in the range of 10–200 nm, developed for biomedical applications provide a wide range of platforms for building and engineering functionalized structures, devices, or systems to fulfill the specific diagnostic and therapeutic needs. Driven by achieving the ultimate goal of clinical translation, sub‐5 nm nano‐constructs, in particular inorganic nanoparticles such as gold, silver, silica, and iron oxide nanoparticles, have been developed in recent years to improve the biocompatibility, delivery and pharmacokinetics of imaging probes and drug delivery systems, as well as in vivo theranostic applications. The emerging studies have provided new findings that demonstrated the unique size‐dependent physical properties, physiological behaviors and biological functions of the nanomaterials in the range of the sub‐5 nm scale, including renal clearance, novel imaging contrast, and tissue distribution. This advanced review attempts to introduce the new strategies of rational design for engineering nanoparticles with the core sizes under 5 nm in consideration of the clinical and translational requirements. We will provide readers the update on recent discoveries of chemical, physical, and biological properties of some biocompatible sub‐5 nm nanomaterials as well as their demonstrated imaging and theranostic applications, followed by sharing our perspectives on the future development of this class of nanomaterials. This article is categorized under:Diagnostic Tools > in vivo Nanodiagnostics and ImagingImplantable Materials and Surgical Technologies > Nanomaterials and Implants [ABSTRACT FROM AUTHOR]

Purpose: To develop a core/shell nanodimer of gold (core) and silver iodine (shell) as a dual-modal contrast-enhancing agent for biomarker targeted x-ray computed tomography (CT) and photoacoustic imaging (PAI) applications. Methods: The gold and silver iodine core/shell nanodimer (Au/AgICSD) was prepared by fusing together components of gold, silver, and iodine. The physicochemical properties of Au/AgICSD were then characterized using different optical and imaging techniques (e.g., HR- transmission electron microscope, scanning transmission electron microscope, x-ray photoelectron spectroscopy, energy-dispersive x-ray spectroscopy, Z-potential, and UV-vis). The CT and PAI contrast-enhancing effects were tested and then compared with a clinically used CT contrast agent and Au nanoparticles. To confer biocompatibility and the capability for efficient biomarker targeting, the surface of the Au/AgICSD nanodimer was modified with the amphiphilic diblock polymer and then functionalized with transferrin for targeting transferrin receptor that is overexpressed in various cancer cells. Cytotoxicity of the prepared Au/AgICSD nanodimer was also tested with both normal and cancer cell lines. Results: The characterizations of prepared Au/AgI core/shell nanostructure confirmed the formation of Au/AgICSD nanodimers. Au/AgICSD nanodimer is stable in physiological conditions for in vivo applications. Au/AgICSD nanodimer exhibited higher contrast enhancement in both CT and PAI for dual-modality imaging. Moreover, transferrin functionalized Au/AgICSD nanodimer showed specific binding to the tumor cells that have a high level of expression of the transferrin receptor. Conclusions: The developed Au/AgICSD nanodimer can be used as a potential biomarker targeted dual-modal contrast agent for both or combined CT and PAI molecular imaging. [ABSTRACT FROM AUTHOR]