In situ self-assembly for cancer therapy and imaging

In situ self-assembly — the in situ formation of complex materials via biochemical reactions of monomers — has enhanced the efficacy of drug delivery for cancer therapy and imaging. So far, nanomedicine has been confined to ex situ self-assembly, which is limited by poor deep-tumour penetration and poor blood circulation. By contrast, in situ self-assembly-based cancer treatments offer various advantages, including enhanced blood circulation of monomers, long-term drug delivery pharmacokinetics, low drug resistance and the ability to target deep tumours and organelles, which can result in disruption-mediated apoptosis and enable the imaging of cellular activity for effective cancer therapy and diagnosis. In this Review, we discuss the design of in situ self-assembled nanomedicines for cancer therapy and imaging based on various endogenous and exogenous stimuli in both the extracellular and the intracellular milieu. We also highlight the advantages of cancer treatment via multimodal dynamic transformations of nanostructures self-assembled in situ, including the ability to induce mechanical stress, deploy cancer-specific targeted therapies, obtain deep-tumour penetration and sustain prolonged drug retention time in the body. Finally, we discuss from a clinical viewpoint the challenges of in situ self-assembled nanomedicine and its potential to offer advanced alternatives to existing cancer therapies. In situ self-assembly is advantageous for cancer therapy and imaging because of the efficient deep-tumour targeting, enhanced blood circulation and negligible drug resistance of the resulting nanomedicines. This Review discusses extracellular and intracellular in situ self-assembly based on endogenous and exogenous stimuli for cancer therapy and imaging applications.