A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer

Goldberg, Manijeh; Manzi, Aaron; Birdi, Amritpreet; LaPorte, Brandon; Conway, Peter; Cantin, Stefanie; Mishra, Vasudha; Singh, Alka; Pearson, Alexander T.; Goldberg, Eric; Goldberger, Sam; Flaum, Benjamin; Hasina, Rifat; London, Nyall R.; Gallia, Gary L.; Bettegowda, Chetan; Young, Simon; Sandulache, Vlad C.; Melville, James C.; Shum, Jonathan; O’Neill, Sonya E.; Aydin, Erkin; Zhavoronkov, Alex; Vidal, Anxo; Soto, Atenea; Alonso, María José; Rosenberg, Ari J.; Lingen, Mark W.; D’Cruz, Anil; Agrawal, Nishant; Izumchenko, Evgeny

doi:10.1038/s41467-022-31859-3

Cited by 30 publications

(18 citation statements)

References 96 publications

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“…Moreover, all secondary endpoints (cisplatin biodistribution, loco-regional control, and technical success) were reached. Finally, no drug-related serious adverse events or locoregional recurrences were reported in 6 months [ 55 ]. In conclusion, the integration of PRV111 with current standard of care may have positive effects on the health outcomes and survival of patients with OCSCC.…”

Section: Resultsmentioning

confidence: 99%

Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment

et al. 2023

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Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently the survival estimate for locally advanced disease is about 50%. The available therapeutic options comprise surgery and pharmacological treatment. Recently, an increased emphasis has been placed on the drugs that might be of benefit in this life-threatening disease. Therefore, the aim of this present review was to offer a general survey of the current available pharmacological treatment for OCSCC. The PubMed database was used to retrieve the papers using “OCSCC” as the search terms. We limited our search to the last 5 years to give a more updated and recent picture of the state of the art, including preclinical and clinical investigations. We found that 77 out of 201 papers were on the surgical treatment of OCSCC, 43 out of 201 focused on the radiotherapy and 81 out of 201 underwent evaluation for the aim of our review. We excluded the case reports, editorial letters, observational studies and papers written in languages other than English. A total of 12 articles were included in the final review. Our results showed that nanotechnologies use to enhance the efficacy of anticancer drugs such as: cisplatin, paclitaxel, cetuximab, EGFR antagonists, MEK1/2 and immune check inhibitors combination could have promising anti-cancer activity. However, the paucity of available data on drugs suggests the urgent need to improve the pharmacological armamentarium for OCSCC treatment.

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Section: Resultsmentioning

confidence: 99%

Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment

et al. 2023

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“…CIS has great potential as a new type of cancer therapy ( Squillace et al, 2022 ). Studies have shown that its effective anticancer activity was due to cuproptosis caused by elevated levels of reactive oxygen species ( Goldberg et al, 2022 ). We have previously performed experiments with isolated mitochondria without copper, thus hindering the identification of the essential role of this ion.…”

Section: Discussionmentioning

confidence: 99%

Curcumin-loaded graphene oxide quantum dots enhance otoprotective effects via blocking cuproptosis

Zhang

Yang

et al. 2023

Front. Bioeng. Biotechnol.

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Graphical AbstractMechanisms by which exposure to cisplatin disrupts the inner ear system are not yet known. Here, we show that cisplatin exposure is associated with dysregulation of oxidative stress in the inner ear of the rodent. Furthermore, we found that, unlike controls, the response parameters of auditory cells of rats exposed to cisplatin were related to an imbalance in copper metabolism. These data suggest that curcumin related changes in the inner ear are depend on their effects on the mechanism of balance of the copper metabolism and that exposure to cisplatin can disrupt the plastic copper metabolism mechanisms needed to restore normal processing in peripheral auditory cells after hearing loss.

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“…OSCC is the most prevalent type of head and neck cancer leading to substantial morbidity and mortality. 1 Conventional treatment types such as surgical resection, radiotherapy, and chemotherapy, [2][3][4] can effectively treat early-stage tumors but are less effective for advanced and metastatic cancers. 5 In recent years, cancer immunotherapy has emerged as a new type of treatment for primary tumors, as activated immune cells can recognize and eradicate residual cancer cells, thereby reducing tumor metastasis and recurrence.…”

Section: Introductionmentioning

confidence: 99%

Graphdiyne Oxide-Mediated Photodynamic Therapy Boosts Enhancive T-Cell Immune Responses by Increasing Cellular Stiffness

Zhang¹,

Pan²,

Huang³

et al. 2023

IJN

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Nanomaterial-based photodynamic therapy (PDT) has been commonly used for the treatment of cancerous tumors. Despite significant achievements made in this field, the intrinsic impact of nanomaterials-based PDT on the mechanical properties of oral squamous cell carcinoma (OSCC) cells is not entirely understood. Here, we used atomic force microscopy (AFM) to measure the stiffness of OSCC cells subjected to PDT in co-culture systems to evaluate the T cell-mediated cancer cell-killing effects. Methods: In this study, AFM was used to assess the stiffness of PDT-subjected cells. The phototoxicity of graphdiyne oxide (GDYO) was assessed using confocal laser scanning microscopy (CLSM), measurements of membrane cholesterol levels, and assessments of the F-actin cytoskeleton. A co-culture system was used to evaluate the effects of CD8 + T cells (cytotoxic T lymphocytes), demonstrating how PDT modulates the mechanical properties of cancer cells and activates T cell responses. The antitumor immunotherapeutic effect of GDYO was further evaluated in a murine xenograft model. Results: GDYO increased the mechanical stiffness of tumor cells and augmented T-cell cytotoxicity and inflammatory cytokine secretion (IFN-γ and TNF-α) under laser in vitro. Furthermore, GDYO-based PDT exerted inhibitory effects on OSCC models and elicited antitumor immune responses via specific cytotoxic T cells. Conclusion: These results highlight that GDYO is a promising candidate for OSCC therapy, shifting the mechanical forces of OSCC cells and breaking through the barriers of the immunosuppressive tumor microenvironment. Our study provides a novel perspective on nanomaterial-based antitumor therapies.

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A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer

Cited by 30 publications

References 96 publications

Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment

Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment

Curcumin-loaded graphene oxide quantum dots enhance otoprotective effects via blocking cuproptosis

Graphdiyne Oxide-Mediated Photodynamic Therapy Boosts Enhancive T-Cell Immune Responses by Increasing Cellular Stiffness

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