Drug-Free Hybrid Nanoarchitecture Modulation of the Metastatic Behavior of Pancreatic Ductal Adenocarcinoma in Alternative <i>in Vivo</i> Models

Zamborlin, Agata; Sarogni, Patrizia; Frusca, Valentina; Gonnelli, Alessandra; Giannini, Noemi; Ermini, Maria Laura; Marranci, Andrea; Pagliari, Francesca; Mazzanti, Chiara Maria; Seco, Joao; Voliani, Valerio

doi:10.1021/acsanm.3c05299

Cited by 4 publications

(1 citation statement)

References 59 publications

(137 reference statements)

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“…metal complexes or hybrid nano-architectures) as well as for the evaluation of the neoplasms’ behaviors 23 – 25 . Indeed, the generation of solid and vascularized neoplasms on the CAM allows for a rapid assessment of the potential tumor-shrinking effect, impairment of vascularization, and/or metastasis modulation of the treatment 26 .…”

Section: Introductionmentioning

confidence: 99%

Tumor growth-arrest effect of tetrahydroquinazoline-derivative human topoisomerase II-alpha inhibitor in HPV-negative head and neck squamous cell carcinoma

Sarogni,

Brindani,

Zamborlin

et al. 2024

Sci Rep

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Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. There is a persisting demand for new approaches to establish more efficient strategies for their treatment. In this regard, the human topoisomerase II (topoII) enzyme is a validated chemotherapeutics target, as topoII regulates vital cellular processes such as DNA replication, transcription, recombination, and chromosome segregation in cells. TopoII inhibitors are currently used to treat some neoplasms such as breast and small cells lung carcinomas. Additionally, topoII inhibitors are under investigation for the treatment of other cancer types, including oral cancer. Here, we report the therapeutic effect of a tetrahydroquinazoline derivative (named ARN21934) that preferentially inhibits the alpha isoform of human topoII. The treatment efficacy of ARN21934 has been evaluated in 2D cell cultures, 3D in vitro systems, and in chick chorioallantoic membrane cancer models. Overall, this work paves the way for further preclinical developments of ARN21934 and possibly other topoII alpha inhibitors of this promising chemical class as a new chemotherapeutic approach for the treatment of oral neoplasms.

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Section: Introductionmentioning

confidence: 99%

Tumor growth-arrest effect of tetrahydroquinazoline-derivative human topoisomerase II-alpha inhibitor in HPV-negative head and neck squamous cell carcinoma

Sarogni,

Brindani,

Zamborlin

et al. 2024

Sci Rep

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Nonpersistent Nanoarchitectures Enhance Concurrent Chemoradiotherapy in an Immunocompetent Orthotopic Model of HPV+ Head/Neck Carcinoma

Gonnelli,

Gerbé de Thoré,

Ermini

et al. 2024

Advanced Materials

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Cisplatin chemoradiotherapy (CRT) is the established standard of care for managing HPV+ head/neck carcinoma. The typically young patients may suffer serious and long‐time side effects caused by the treatment, such as dysphagia, and hearing loss. Thus, ensuring a satisfactory post‐treatment quality of life is paramount. One potential replacing approach to the classical CRT involves the combination of standard‐dose radiotherapy and radiosensitizers such as noble metal nanoparticles (NPs). However, several concerns about size, shape and biocompatibility limit the translation of metal nanomaterials to the clinical practice. Here, we demonstrate that a new model of non‐persistent gold nano‐architectures containing cisplatin (NAs‐Cluster‐CisPt) generates, in combination with radiotherapy, a significant in vivo tumor‐reducing effect compared to the standard CRT, achieving a complete tumor clearance in 25% of the immunocompetent models that persisted for 60 days. These findings, together with the negligible amount of metals recognized in the excretory organs, highlight that the concurrent administration of NAs‐Cluster‐CisPt and radiotherapy has the potential to overcome some clinical limitations associated to NPs‐based approaches while enhancing the treatment outcome respect to standard CRT. Overall, despite further mechanistic investigations being essential, our data support the exploiting of non‐persistent metal nanomaterials mediated approaches for oral cancer management.This article is protected by copyright. All rights reserved

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In Vivo Combined Photoacoustic Imaging and Photothermal Treatment of HPV‐Negative Head and Neck Carcinoma with NIR‐Responsive Non‐Persistent Plasmon Nano‐Architectures

Frusca,

Cavallini,

Zamborlin

et al. 2024

Advanced Therapeutics

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The combination of photoacoustic imaging (PAI) and photothermal therapy (PTT) is an attractive approach in cancer management due to the non‐invasive features combined with real‐time imaging and selective tissue damage by non‐ionizing radiation. This approach is especially appealing for Head and Neck Squamous Cell Carcinoma (HNSCC) management, where up to 40% of patients require modifications of the treatment regimen. On the other hand, most of the agents developed for PAI/PTT suffer from persistence or re‐shaping issues. Here, a unique non‐persistent plasmon nano‐architecture (tNAs‐IRDye) is presented that simultaneously acts as a contrast agent for PAI and as a photothermal transducer for PTT. The tNAs‐IRDye are fully characterized and evaluated in vitro and ex vivo, and their performance as theranostic agents is assessed in HPV‐negative HNSCC murine models. A significant modulation of tumor growth is obtained in vivo upon intratumoral injection of tNAs‐IRDye and subsequent NIR irradiation compared to the solely irradiated control. The outcomes of this study exhibit a noteworthy potential to foster the development of innovative clinical strategies for the management of HPV‐negative head and neck carcinoma.

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Drug-Free Hybrid Nanoarchitecture Modulation of the Metastatic Behavior of Pancreatic Ductal Adenocarcinoma in Alternative in Vivo Models

Cited by 4 publications

References 59 publications

Tumor growth-arrest effect of tetrahydroquinazoline-derivative human topoisomerase II-alpha inhibitor in HPV-negative head and neck squamous cell carcinoma

Tumor growth-arrest effect of tetrahydroquinazoline-derivative human topoisomerase II-alpha inhibitor in HPV-negative head and neck squamous cell carcinoma

Nonpersistent Nanoarchitectures Enhance Concurrent Chemoradiotherapy in an Immunocompetent Orthotopic Model of HPV+ Head/Neck Carcinoma

In Vivo Combined Photoacoustic Imaging and Photothermal Treatment of HPV‐Negative Head and Neck Carcinoma with NIR‐Responsive Non‐Persistent Plasmon Nano‐Architectures

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