Decreasing hyaluronic acid combined with drug-loaded nanoprobes improve the delivery and efficacy of chemotherapeutic drugs for pancreatic cancer

Fan, Ying-Fang; Shang, Wenting; Lu, Guanhua; Guo, Kunxiong; Deng, Han; Zhu, Xinhong; Wang, Cunchuan; Tian, Jie

doi:10.1016/j.canlet.2021.09.016

Cited by 12 publications

(7 citation statements)

References 36 publications

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“…Studies have shown that loading extracellular matrix (ECM)-degrading enzymes such as relaxin, metalloproteinase and hyaluronidase on oncolytic viruses can facilitate the penetration and dissemination of viruses and drugs within tumors [ 20 , 21 , 22 , 23 ]. Therefore, we selected hyaluronidase PH20 as the first exogenous gene loaded on the PRV vector to reformulate the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated the efficacy of IL-18 , IFN-γ and PH20 in cancer treatment [ 10 , 22 , 30 , 31 , 32 , 33 , 34 ], but the therapeutic potential of their combination has not been previously reported. Our hypothesis was that the co-administration of IL-18 , IFN-γ and PH20 with the PRV oncolytic virus would result in a superior antitumor effect based on the properties of these immunostimulatory molecules.…”

Section: Discussionmentioning

confidence: 99%

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A Recombinant Oncolytic Pseudorabies Virus Expressing Interleukin-18, Interferon-Gamma and PH20 Genes Promotes Systemic Antitumor Immunity

Han

Sun

et al. 2023

Microorganisms

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Pseudorabies virus (PRV) is considered to be a promising oncolytic virus that has potential as a cancer gene therapy drug. In this study, PRV-DCD-1-70 was used as a vector to carry exogenous genes IL-18, IFN-γ and PH20 to construct novel recombinant PRV, rPRV-PH20 and rPRV-IL-18-γ-PH20, and their tumorolytic effects were evaluated in vitro and in vivo. Our study showed that recombinant PRV lysed all four tumor cell lines, Pan02, EMT-6, CT26 and H446, and rPRV-IL-18-γ-PH20 showed the best tumor lysis effect. Further studies in mice bearing Pan02 tumors showed that recombinant PRV, especially rPRV-IL-18-γ-PH20, were able to inhibit tumor growth. Moreover, an immunohistochemical analysis indicated that the recombinant PRV effectively increased the infiltration of CD4+T and CD8+T cells and enhanced the anti-tumor immune response of the organism in vivo. Overall, PRV carrying PH20 and IL-18-γ exogenous genes demonstrated anti-tumor effects, providing a foundation for the further development and application of PRV as a novel tumor oncolytic virus vector.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Recombinant Oncolytic Pseudorabies Virus Expressing Interleukin-18, Interferon-Gamma and PH20 Genes Promotes Systemic Antitumor Immunity

Han

Sun

et al. 2023

Microorganisms

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“… TME modulator combination therapies [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Various agents that modulate the production of stromal components and/or signaling in the TME have been investigated to overcome resistance to anticancer therapies.…”

Section: Figurementioning

confidence: 99%

Nanomedicine Strategies for Targeting Tumor Stroma

Su,

Nethi,

Dhanyamraju

et al. 2023

Cancers

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The tumor stroma, or the microenvironment surrounding solid tumors, can significantly impact the effectiveness of cancer therapies. The tumor microenvironment is characterized by high interstitial pressure, a consequence of leaky vasculature, and dense stroma created by excessive deposition of various macromolecules such as collagen, fibronectin, and hyaluronic acid (HA). In addition, non-cancerous cells such as cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM) itself can promote tumor growth. In recent years, there has been increased interest in combining standard cancer treatments with stromal-targeting strategies or stromal modulators to improve therapeutic outcomes. Furthermore, the use of nanomedicine, which can improve the delivery and retention of drugs in the tumor, has been proposed to target the stroma. This review focuses on how different stromal components contribute to tumor progression and impede chemotherapeutic delivery. Additionally, this review highlights recent advancements in nanomedicine-based stromal modulation and discusses potential future directions for developing more effective stroma-targeted cancer therapies.

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“…Thus, most patients miss opportunities for radical surgical resection in the early stage and can only undergo radiotherapy and chemotherapy later. However, owing to the special extracellular matrix barrier of pancreatic cancer and resistance to chemotherapeutic drugs, some cancer cells cannot be killed [ 9 , 10 ]. Furthermore, approximately 40% of patients with PDAC experience tumor recurrence even after surgical resection and die within one year [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cell-Based Targeted Therapy Pancreatic Cancer: Progress and Challenges

Hua

Liu

et al. 2023

IJMS

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Pancreatic cancer is an aggressive malignancy with high mortality rates and poor prognoses. Despite rapid progress in the diagnosis and treatment of pancreatic cancer, the efficacy of current therapeutic strategies remains limited. Hence, better alternative therapeutic options for treating pancreatic cancer need to be urgently explored. Mesenchymal stromal cells (MSCs) have recently received much attention as a potential therapy for pancreatic cancer owing to their tumor-homing properties. However, the specific antitumor effect of MSCs is still controversial. To this end, we aimed to focus on the potential anti-cancer treatment prospects of the MSC-based approach and summarize current challenges in the clinical application of MSCs to treat pancreatic cancer.

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Decreasing hyaluronic acid combined with drug-loaded nanoprobes improve the delivery and efficacy of chemotherapeutic drugs for pancreatic cancer

Cited by 12 publications

References 36 publications

A Recombinant Oncolytic Pseudorabies Virus Expressing Interleukin-18, Interferon-Gamma and PH20 Genes Promotes Systemic Antitumor Immunity

A Recombinant Oncolytic Pseudorabies Virus Expressing Interleukin-18, Interferon-Gamma and PH20 Genes Promotes Systemic Antitumor Immunity

Nanomedicine Strategies for Targeting Tumor Stroma

Mesenchymal Stromal Cell-Based Targeted Therapy Pancreatic Cancer: Progress and Challenges

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