Tumor microenvironment-triggered intratumoral in situ construction of theranostic supramolecular self-assembly

As one typical intratumoral nanosynthetic medicine (INSM), in situ biosynthesized supramolecular self-assemblies point at the accurate transformation of disordered small molecules into stable, morphology-defined and function-specific polymers by tumor microenvironment (TME) stimuli-unlocked intermolecular forces at objective locations. This artificially-manipulated spatiotemporal synthesis strategy is one main direction of current biomedical development. Aiming at the aberrant microenvironment, precisely and controllably constructing theranostic nano-sized self-assemblies with highly sensitive and specific responses to special TME or trigger at the target location of tumor is highly emphasized and regarded as a great breakthrough in biomedicine. This technology is expected to provide new ideas for the artificially controllable self-assembly of small molecule nanomaterials into dynamic smart nanomedicines in living cells and permit to improve the delivery and retention of current self-assembly systems. This review summarized the recent progress and rationales of intratumoral stimuli-responsive in situ assembly of supramolecular self-assemblies based on artificial small molecule nanomaterials in tumors, and clarified how and why these TME triggers can trigger artificial small molecule to self-assembles. Moreover, the tumor-related stimulatory response components were discussed and the intermolecular driving forces or interactions after TME-triggered precursor cleavage were summarized, wherein the unique design concepts and the corresponding application innovation in the field of tumor diagnosis and treatment were clearly shed light on using some classic examples. Ultimately, the prospects, challenges that the intratumoral stimuli-responsive supramolecular self-assembly synthesis faced, and the potential solutions were put forward to deepen the understanding of future biomedical application and clinical translation.