Bonferoni Maria Cristina, Rassu Giovanna, Gavini Elisabetta, Sorrenti Milena, Catenacci Laura, Torre Maria Luisa, Perteghella Sara, Ansaloni Luca, Maestri Marcello, Giunchedi Paolo
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
Department of Chemistry and Pharmacy, University of Sassari, Via Muroni 23/a, 07100 Sassari, Italy.
Cancers (Basel). 2021 Sep 3;13(17):4437. doi: 10.3390/cancers13174437.
Surgical resection is the gold standard for the treatment of many kinds of tumor, but its success depends on the early diagnosis and the absence of metastases. However, many deep-seated tumors (liver, pancreas, for example) are often unresectable at the time of diagnosis. Chemotherapies and radiotherapies are a second line for cancer treatment. The "enhanced permeability and retention" (EPR) effect is believed to play a fundamental role in the passive uptake of drug-loaded nanocarriers, for example polymeric nanoparticles, in deep-seated tumors. However, criticisms of the EPR effect were recently raised, particularly in advanced human cancers: obstructed blood vessels and suppressed blood flow determine a heterogeneity of the EPR effect, with negative consequences on nanocarrier accumulation, retention, and intratumoral distribution. Therefore, to improve the nanomedicine uptake, there is a strong need for "EPR enhancers". Electrochemotherapy represents an important tool for the treatment of deep-seated tumors, usually combined with the systemic (intravenous) administration of anticancer drugs, such as bleomycin or cisplatin. A possible new strategy, worthy of investigation, could be the use of this technique as an "EPR enhancer" of a target tumor, combined with the intratumoral administration of drug-loaded nanoparticles. This is a general overview of the rational basis for which EP could be envisaged as an "EPR enhancer" in nanomedicine.
手术切除是多种肿瘤治疗的金标准，但其成功取决于早期诊断和无转移情况。然而，许多深部肿瘤（例如肝脏、胰腺肿瘤）在诊断时往往无法切除。化疗和放疗是癌症治疗的二线方法。“增强渗透与滞留”（EPR）效应被认为在深部肿瘤中载药纳米载体（例如聚合物纳米颗粒）的被动摄取中起关键作用。然而，最近对EPR效应提出了批评，特别是在晚期人类癌症中：血管阻塞和血流抑制决定了EPR效应的异质性，对纳米载体的积累、滞留和肿瘤内分布产生负面影响。因此，为了提高纳米药物的摄取，迫切需要“EPR增强剂”。电化学疗法是治疗深部肿瘤的重要工具，通常与抗癌药物（如博来霉素或顺铂）的全身（静脉）给药联合使用。一种值得研究的可能新策略是将该技术用作靶肿瘤的“EPR增强剂”，并结合瘤内注射载药纳米颗粒。这是将电化学疗法设想为纳米医学中“EPR增强剂”的合理依据的总体概述。
