Hyperthermic nanomedicines are particularly relevant for tackling human cancer, providing a valuable alternative to conventional therapeutics. The early-stage preclinical performance evaluation of such anti-cancer treatments is conventionally performed in flat 2D cell cultures that do not mimic the volumetric heat transfer occurring in human tumors. Recently, improvements in bioengineered 3D in vitro models have unlocked the opportunity to recapitulate major tumor microenvironment hallmarks and generate highly informative readouts that can contribute to accelerating the discovery and validation of efficient hyperthermic treatments. Leveraging on this, herein we aim to showcase the potential of engineered physiomimetic 3D tumor models for evaluating the preclinical efficacy of hyperthermic nanomedicines, featuring the main advantages and design considerations under diverse testing scenarios. The most recent applications of 3D tumor models for screening photo- and/or magnetic nanomedicines will be discussed, either as standalone systems or in combinatorial approaches with other anti-cancer therapeutics. We envision that breakthroughs toward developing multi-functional 3D platforms for hyperthermia onset and follow-up will contribute to a more expedited discovery of top-performing hyperthermic therapies in a preclinical setting before their in vivo screening.

中文翻译：

---

在3D肿瘤模型中筛选热纳米药物的进展

热纳米药物对于治疗人类癌症特别重要，为传统疗法提供了有价值的替代方案。此类抗癌治疗的早期临床前性能评估通常在平面二维细胞培养物中进行，该细胞培养物不模拟人类肿瘤中发生的体积传热。最近，生物工程 3D体外模型的改进释放了重述主要肿瘤微环境特征并生成信息丰富的读数的机会，这有助于加速有效热疗治疗的发现和验证。在此基础上，我们旨在展示工程拟体 3D 肿瘤模型在评估热纳米药物临床前疗效方面的潜力，并展示不同测试场景下的主要优势和设计考虑因素。将讨论 3D 肿瘤模型在筛选光和/或磁性纳米药物方面的最新应用，无论是作为独立系统还是与其他抗癌疗法的组合方法。我们预计，在开发用于热疗起始和随访的多功能 3D 平台方面取得的突破将有助于在体内筛选之前在临床前环境中更快地发现性能最佳的热疗疗法。