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作为新疗法靶点的 PDA 的代谢和结构:纳米技术的可能性和局限性。

Metabolism and structure of PDA as the target for new therapies: possibilities and limitations for nanotechnology.

机构信息

Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.

出版信息

Expert Opin Drug Deliv. 2024 Jun;21(6):845-865. doi: 10.1080/17425247.2024.2370492. Epub 2024 Jun 25.

DOI:10.1080/17425247.2024.2370492
PMID:38899424
Abstract

INTRODUCTION

Certainly, pancreatic ductal adenocarcinoma poses one of the greatest challenges in current oncology. The dense extracellular matrix and low vessel density in PDA tumor impede the effective delivery of drugs, primarily due to the short pharmacokinetics of most drugs and potential electrostatic interactions with stroma components.

AREA COVERED

Owing to the distinctive metabolism of PDA and challenges in accessing nutrients, there is a growing interest in cell metabolism inhibitors as a potential means to inhibit cancer development. However, even if suitable combinations of inhibitors are identified, the question about their administration remains, as the same hindrances that impede effective treatment with conventional drugs will also hinder the delivery of inhibitors. Methods including nanotechnology to increase drugs in PDA penetrations are reviewed and discussed.

EXPERT OPINION

Pancreatic cancer is one of the most difficult tumors to treat due to the small number of blood vessels, high content of extracellular matrix, and specialized resistance mechanisms of tumor cells. One possible method of treating this tumor is the use of metabolic inhibitors in combinations that show synergy. Despite promising results in tests, their effect is uncertain due to the tumor's structure. In the case of pancreatic cancer, priming of the tumor tissue is required through the sequential administration of drugs that generate blood vessels, increase blood flow, and enhance vascular permeability and extracellular matrix. The use of drug carriers with a size of 10-30 nm may be crucial in the therapy of this cancer.

摘要

简介

胰腺导管腺癌是当前肿瘤学面临的最大挑战之一。PDA 肿瘤中致密的细胞外基质和低血管密度阻碍了药物的有效传递,这主要是由于大多数药物的药代动力学较短,以及与基质成分的潜在静电相互作用。

涵盖领域

由于 PDA 的独特代谢和获取营养物质的挑战,细胞代谢抑制剂作为抑制癌症发展的潜在手段越来越受到关注。然而,即使确定了合适的抑制剂组合,关于其给药的问题仍然存在,因为阻碍常规药物有效治疗的相同障碍也将阻碍抑制剂的传递。本文回顾和讨论了包括纳米技术在内的增加 PDA 药物渗透的方法。

专家意见

由于血管数量少、细胞外基质含量高以及肿瘤细胞的特殊耐药机制,胰腺癌是最难治疗的肿瘤之一。治疗这种肿瘤的一种可能方法是联合使用代谢抑制剂,以显示协同作用。尽管在测试中取得了有希望的结果,但由于肿瘤的结构,其效果仍不确定。在胰腺癌的情况下,需要通过序贯给予药物来对肿瘤组织进行预处理,这些药物可以生成血管、增加血流量、增强血管通透性和细胞外基质。使用大小为 10-30nm 的药物载体可能对这种癌症的治疗至关重要。

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