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Bioorthogonal enzyme-mimicking catalyst for in situ drug synthesis (Virtual; Virtual Session (Virtual Only)) - Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_13860;
As an example of hydrogen-bonded organic framework-based bioorthogonal enzyme-mimicking catalytic strategy, this work provides insights into prevention of drug inactivation by using bioorthogonal chemistry, thus enhancing tumor inhibition and reducing therapeutic side effects demonstrated by both in vitro and orthotopic metastatic mouse model. HOF-based bioorthogonal prodrugs activation for chemotherapy
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Journal: Oxygen-producing and pH-responsive targeted DNA nanoflowers for enhanced chemo-sonodynamic therapy of lung cancer. (Pubmed Central) - Mar 6, 2024
In order to overcome these problems, we have designed a drug-loaded targeted DNA nanoflowers encoding AS1411 aptamer and encapsulating chemotherapeutic drug doxorubicin and oxygen-producing drug horseradish peroxidase (DOX/HRP-DFs)...It is noteworthy that both in vitro and in vivo experiments demonstrated DNA nanoflowers could considerably improve the hypoxia of tumor cells, which enabled the generation of sufficient reactive oxygen species in combination with ultrasound, significantly enhancing the therapeutic effect of sonodynamic therapy and evidently inhibiting tumor growth and metastasis. Overall, this DNA nanoflowers delivery system offers a promising approach for treating lung cancer.
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Targeting a novel TWIST1-Hexokinase II pathway to overcome MET TKI resistance in NSCLC (Section 30) - Mar 5, 2024 - Abstract #AACR2024AACR_6767;
Conversely, treatment of MET amplified cells with MET TKI, capmatinib, reduced glycolysis and oxidation phosphorylation to the levels observed in MET wild type LUAD lines...These findings suggest that continued upregulation of the TWIST1-HK2 axis is required for acquired MET TKI resistance. In summary, these studies suggest a targetable, metabolic reprogramming in MET altered LUAD BM mediated through a novel TWIST1-HK2 pathway.
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Journal: Activable Photodynamic DNA Probe with an "AND" Logic Gate for Precision Skin Cancer Therapy. (Pubmed Central) - Jan 25, 2024
The ADP incorporated an AS1411 aptamer for tumor targeting and a linear antisense oligonucleotide (ASO) for recognition of Survivin mRNA...The resulting functionalized G-quadruplex/hemin-DNA probe complex demonstrated targeted delivery and activation, minimized side effects, and enhanced PDT efficacy in both xenograft tumor-bearing mice and patient-derived xenograft models. This study offers a unique and promising platform for efficient and safe PDT, thus holding great potential for future clinical translation and improved cancer therapy.
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Journal, Combination therapy: Self-Propelled Nanomotor for Cancer Precision Combination Therapy. (Pubmed Central) - Jan 23, 2024
The modification of nucleic acid aptamer and NIR-II fluorescent molecules on its surface simultaneously strengthens both the active targeting and imaging capability of tumor loci. Therefore, by a comprehensive assessment of nanomotors both in vitro and in vivo experiments, CaO /DOX@HPS-IR-1061-AS1411 demonstrated superior killing effects on tumor cells, and the intracellular reactive oxygen species produced by nanomotors was verified by molecular biology experiments to induce apoptosis of tumor cells and further achieve tumor therapeutic effects.
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Journal: Nucleolin-RNA interaction modulates rotavirus replication. (Pubmed Central) - Jan 19, 2024
To determine whether the nucleolin-RNA interaction regulates RRV replication, MA104 cells were transfected with AGRO100, a compound that forms G4 structures and selectively inhibits nucleolin-RNA interactions by blocking the RNA-binding domains...Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.
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Journal: "Light-On" Fluorescent Nanoprobes for Monitoring Dynamic Distribution of Cellular Nucleolin During Pyroptosis. (Pubmed Central) - Jan 17, 2024
Here, we designed "turn-on" fluorescent nanoprobes composed of specific AS1411 aptamer and nucleus-targeting peptide on gold nanoparticles (AuNPs) to effectively capture and track the NCL distribution and expression during pyroptosis triggered by electrical stimulation (ES)...Compared with normal cells (MCF-10A), NCL is overexpressed within cancerous cells (MCF-7 cells) using the as-designed nanoprobes, and the ES can effectively inhibit NCL expression within cancerous cells. The developed NCL sensing platform and ES-based methods hold great potential for cellular studies of cancer-related diseases.
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Review, Journal: Clinical advances in TNC delivery vectors and their conjugate agents. (Pubmed Central) - Jan 15, 2024
ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.
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Journal: Aptamer-Modified Tetrahedral Dna Nanostructures as Drug Delivery System for Cancer Targeted Therapy. (Pubmed Central) - Dec 13, 2023
The DNA tetrahedron was composed of a tetrahedral DNA nanostructure (TDN) with two strands of AS1411 aptamer as recognition elements which could target the nucleolin protein on the cell membrane of cancer cells...The proposed drug delivery system exhibited significant therapeutic efficacy in vitro compared to free Dox. Accordingly, this work provided a good paradigm for developing a targeted drug delivery system for cancer therapy based on DNA tetrahedrons.
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Journal: Luminescent Gold Nanoparticles with Discrete DNA Valences for Precisely Controlled Transport at the Subcellular Level. (Pubmed Central) - Dec 7, 2023
Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near-infrared window using a phosphorothioate-modified DNA aptamer, AS1411, as a template...A slight increase in valence from V1 to V2 increased tumor-targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor-targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.
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Journal: Spindle Monitor: A Tool for Real-Time Assessment and Concurrent Treatment of Postoperative Tumor Prognosis. (Pubmed Central) - Dec 6, 2023
Specifically, our "Spindle Monitor" APPADs had been validated to achieve accurate fluorescence imaging in vitro and in vivo, which demonstrated its potential value as a versatile tool for evaluating postoperative prognosis in surgical treatments, such as thyroid cancer, and assessing chemotherapy efficacy in difficult cases, like late-stage osteosarcoma. This promising tool lays a good foundation for development in visual prognosis evaluation after tumor surgery.
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Journal: Investigation of the Relationship between Aptamers' Targeting Functions and Human Plasma Proteins. (Pubmed Central) - Dec 4, 2023
In order to maintain the targeting function in the physiological milieu, a series of optimizations were performed via the chemical modifications of AS1411 aptamer, and 3'-terminal pegylation was demonstrated to be resistant to the interaction with FN1, leading to improved tumor-targeting effects. This work emphasizes the physiological environment influences on aptamers targeting functionality and suggests that rational design and modification of aptamers to minimize the nonspecific interaction with plasma proteins might be effective to maintain aptamer functionality in future clinical uses.
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Preclinical, Journal: Azo Reductase Activated Magnetic Resonance Tuning Probe with "Switch-On" Property for Specific and Sensitive Tumor Imaging in Vivo. (Pubmed Central) - Nov 22, 2023
Specifically, Gd-labeled DNA (DNA-Gd) and cyclodextrin-coated magnetic nanoparticles (MNP-CD) were employed as enhancer and quencher of MRET, respectively, while DNA, an azobenzene (Azo) group-modified aptamer (AS1411), served as a linker between enhancer and quencher to construct the MRET probe of MNP@DNA-Gd...Moreover, the tumor with a 4 times smaller size than that of the normal tumor model could be imaged based on the proposed MRET probe. The as-proposed MRET-based magnetic resonance imaging strategy not only achieves tumor imaging accurately but also shows promise for early diagnosis of tumors, which might improve patients' survival rates and provide an opportunity for image-guided biomedical applications in the future.
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Journal: A Versatile G-quadruplex (G4)-coated Upconverted Metal-Organic Framework for Hypoxic Tumor Therapy. (Pubmed Central) - Nov 13, 2023
When irradiated with near-infrared (NIR) light, the UMGH antitumor properties were bolstered by photodynamic therapy (PDT), thanks to its ability to convert O into singlet oxygen ( O ). Combined with the antiproliferative activity of AS1411-A, this novel approach herein lays the foundation for a new type of G4-based nanomedicine.
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Journal: Insights on the molecular mechanisms of cytotoxicity induced by AS1411 linked to folate-functionalized DNA nanocages in cancer cells. (Pubmed Central) - Nov 6, 2023
RNA-seq analysis allowed to identify biological functions and genes altered by the various treatments, depending on the AS1411 route of intracellular entry, highlighting the different behavior of the two cancer cell lines. Notably, Fol-Apt-NCs altered the expression of a subset of genes associated to cancer chemoresistance in MDA-MB-231, but not in HeLa cells, and this may explain the increased chemosensitivity to drugs delivered through DNA nanocages of the triple negative breast cancer cells.
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Journal: Ultrasound-Induced Gold Nanoparticle United with Acoustic Reprogramming of Macrophages for Enhanced Cancer Therapy. (Pubmed Central) - Oct 25, 2023
The hybrid nanomachine was assembled with gold nanoparticles (GNPs) as the core and encapsulated with macrophage exosomes modified by AS1411 aptamers (GNP@EXO-APs) to optimize the pharmacokinetics and tumor aggregation...Enhanced mechanical destruction via GNP@EXO-APs and immunotherapy of cancer cells were verified both in vitro and in vivo under SDT. This study provides a new direction for inside-out killing effects on tumor cells for cancer treatment.
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Journal: Enhancing the sensitization of neuroblastoma to radiotherapy by the construction of a dual-channel parallel free radicals nanoamplifier. (Pubmed Central) - Oct 12, 2023
The released ATO dramatically inhibited the mitochondrial respiration of tumor cells, thus sparing vast amounts of oxygen for the generation of free radicals during RT process, which was the first free radicals-amplifying pathway Meanwhile, the released Fe could consume the tumor-overexpressed GSH through the redox reaction, thus effectively preserving the generated free radicals in RT process, which was the second free radicals-amplifying pathway. Taken together, our study demonstrates a dual-channel parallel free radicals-amplifying RT strategy, and it is expected this work will promote the clinical application prospects of RT treatment against neuroblastoma.
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Review, Journal: Anti-nucleolin aptamer AS1411: an advancing therapeutic. (Pubmed Central) - Oct 9, 2023
AS1411 can also be bound to nanoparticles capable of detecting nucleolin at concentrations far lower than lab techniques used today for cancer diagnosis. AS1411 has a promising potential to change cancer diagnoses and treatment.
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Journal: A Multifunctional Delivery System for Remodulating Cell Behaviors of Circulating Malignant Cells to Prevent Cell Fusion. (Pubmed Central) - Aug 17, 2023
The multifunctional delivery vector decorated by AS1411 conjugated hyaluronic acid and NLS-GE11 peptide conjugated hyaluronic acid can specifically target circulating malignant cells (CMCs) of cancer patients to deliver the genome editing plasmid for epidermal growth factor receptor (EGFR) knockout...After EGFR knockout, the edited CMCs exhibit dramatically inhibited cell fusion capability, while unedited CMCs can easily fuse with human umbilical vein endothelial cells (HUVEC) to form hybrid cells. This study provides a new therapeutic strategy for preventing cancer progression and a reliable tool for evaluating cancer cell fusion for precise personalized therapy.
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Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.
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Journal, Gene therapy: Framework Nucleic Acid-Based Multifunctional Tumor Theranostic Nanosystem for miRNA Fluorescence Imaging and Chemo/Gene Therapy. (Pubmed Central) - Jul 21, 2023
Strikingly, both in vitro and in vivo experiments demonstrated the achievements of the FNA-enabled miR-21 imaging and synergistically enhanced chemo/gene therapy. This work thus represents a noteworthy advance on the FNA-based theranostic strategy that can effectively avoid the undesirable premature leakage of anticarcinogen and off-target of siRNA, and achieve on-demand reagents release for tumor diagnostics and treatment.
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Journal: Functional Nucleic Acids-Engineered Bio-Barcode Nanoplatforms for Targeted Synergistic Therapy of Multidrug-Resistant Cancer. (Pubmed Central) - Jul 17, 2023
The multivalent AS1411 aptamers equipped in ZnO@BBCs facilitate specific and efficient endocytosis into MDR human lung adenocarcinoma cells (A549/DDP)...On the other hand, the silence of early growth response protein 1 (Egr-1) mRNA by Zn-dependent DNAzymes directly inhibits the proliferation and migration of MDR cells, which further suppresses the P-glycoprotein (P-gp)-mediated drug efflux. Thus, the proposed nanoplatforms show great promise for the development of versatile therapeutic tools and personalized nanomedicines for MDR cancers.
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Journal: In Situ Activation of the Receptor Aggregation for Cell Apoptosis by an AI-Au Intelligent Nanomachine via Tumor Extracellular Acidity. (Pubmed Central) - Jul 14, 2023
Dual functional ssDNA (AS1411 aptamer and pH-responsive I-strand sequence) was modified on the surface of gold nanoparticles (AuNPs) to fabricate AI-Au intelligent nanomachines...The proposed strategy used for specific cancer cell apoptosis by the in situ activation of tumor cell membrane receptor aggregation is inexpensive and simple to use, which not only provides a new means of nucleolin receptor aggregation for regulating cell function but also offers a new strategy for tumor treatment with reduced side effect to normal cells. This work is significant for comprehending the ligand-induced receptor aggregation process and can lead to the development of a promising anticancer drug.
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Journal: Modular DNA Tetrahedron Nanomachine-Guided Dual-Responsive Hybridization Chain Reactions for Discernible Bivariate Assay and Cell Imaging. (Pubmed Central) - Jul 12, 2023
Motivated by this knowledge, a dual-responsive DNA tetrahedron nanomachine (drDT-NM) is constructed through immobilizing two recognition modules, MUC1 aptamer (MA) and a hairpin H1* encoding nucleolin-specific G-rich AS1411 aptamer, in two separate vertexes of a functional DT architecture tethering two localized pendants (P and P)...The tandem ZnPPIX/G4 unities also act as imaging agents and therapeutic cargos for efficient photodynamic therapy of cancer cells. Based on drDT-NM to guide bispecific HCR amplifiers for adaptive bivariate detection, we present a paradigm of exquisitely integrating modular DNA nanostructures with nonenzymatic nucleic acid amplification, thus creating a versatile biosensing platform as a promising candidate for accurate assay, discernible cell imaging, and targeted therapy.
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Journal: An insight into fluorescence and magnetic resonance bioimaging using a multifunctional polyethyleneimine-passivated gadocarbon dots nanoconstruct assembled with AS1411. (Pubmed Central) - Jun 30, 2023
Importantly, the as-prepared Gd@CDs, Gd@CDs-PEI1, and Gd@CDs-PEI2 exhibit higher longitudinal relaxivity values (r) compared with the commercial Gd-DTPA, equal to 5.212, 7.488, and 5.667 mMs, respectively. Accordingly, it is concluded that the prepared nanoassemblies have the potential to become excellent candidates for cancer targeting and fluorescence/MR imaging agents, which can be applied to cancer imaging and personalized nanomedicine.
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