Scheme 1.

Illustration of the circulation fate of a supramolecular polymer (SP) after entering into the circulation. SP (1) may dissociate into fragments/monomers in the plasma upon dilution, and the dissociation kinetics is mostly dictated by its CMC. SP has the tendency to accumulate more in the tumor (2) and major organs (3) (liver, spleen, kidney, lung, and heart), while fragments/monomers (4) tend to undergo a rapid renal clearance. Thus, the lower the CMC of a SP, the lower the percentage of fragments and monomers, leading to reduced excretion and enhanced tumor (improved efficacy) and healthy organ uptake (increased toxicity).