Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization and the opportunity to monitor response to therapy. Here, we report a multimodal nanosensor engineered to target tumours through acidosis, respond to proteases in the microenvironment to release urinary reporters and (optionally) carry positron emission tomography probes to enable localization of primary and metastatic cancers in mouse models of colorectal cancer. We present a paradigm wherein this multimodal sensor can be employed longitudinally to assess burden of disease non-invasively, including tumour progression and response to chemotherapy. Specifically, we showed that acidosis-mediated tumour insertion enhanced on-target release of matrix metalloproteinase-responsive reporters in urine. Subsequent on-demand loading of the radiotracer ⁶⁴Cu allowed pH-dependent tumour visualization, enabling enriched microenvironmental characterization when compared with the conventional metabolic tracer ¹⁸F-fluorodeoxyglucose. Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumour types.

精准诊断可能有助于肿瘤学的治疗结果，这些精准诊断可提供早期检测、定位和监测治疗反应的机会。在这里，我们报告了一种多模式纳米传感器，该传感器设计用于通过酸中毒靶向肿瘤，对微环境中的蛋白酶做出反应以释放尿液报告分子，并（可选）携带正电子发射断层扫描探针，以在结直肠癌小鼠模型中定位原发性和转移性癌症。我们提出了一种范例，其中可以纵向使用这种多模式传感器来非侵入性地评估疾病负担，包括肿瘤进展和对化疗的反应。具体来说，我们发现酸中毒介导的肿瘤插入增强了尿液中基质金属蛋白酶反应报告基因的靶向释放。^{与传统的代谢示踪剂18 F-氟脱氧葡萄糖相比， 64} Cu 允许 pH 依赖性肿瘤可视化，从而能够丰富微环境表征。通过定制的目标特异性，这个模块化平台有能力被设计成一种泛癌测试，可以指导多种肿瘤类型的治疗决策。