Microenvironment-triggered multimodal precision diagnostics.
Liangliang HaoNazanin RohaniRenee T ZhaoEmilia M PulverHoward MakOlivia J KeladaHenry KoSangeeta N BhatiaFrank B GertlerSangeeta N BhatiaPublished in: Nature materials (2021)
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.
Keyphrases
- positron emission tomography
- computed tomography
- pet imaging
- pain management
- pet ct
- stem cells
- small cell lung cancer
- mouse model
- squamous cell carcinoma
- small molecule
- papillary thyroid
- type diabetes
- locally advanced
- radiation therapy
- living cells
- adipose tissue
- chronic pain
- weight loss
- childhood cancer
- rectal cancer
- chemotherapy induced