Multiscale Self-Assembly of a Phenyl-Flanked Diketopyrrolopyrrole Derivative: A Solution-Processable Building Block for π-Conjugated Supramolecular Polymers.

We report a solution-processable π-conjugated molecular building block (denoted as PhDPP) consisting of a rigid and planar core of phenyl-flanked diketopyrrolopyrrole and "soft" branched alkoxy chains that endow the solubility in a variety of organic solvents. Intermolecular hydrogen bonding in PhDPP was revealed in nonpolar solvents above a threshold of concentration and below a critical point of temperature. The strong intermolecular interaction mainly contributed by the hydrogen-bonding and π-π interaction between PhDPP molecules promoted the formation of supramolecular polymeric structures in both solution and solid states and at interfaces. The supramolecular polymeric properties enabled solution-based processing of PhDPP under a variety of conditions into different structures including fibers and uniform thin films. The structure-property relationship that we established in the present system of PhDPP from the molecular to supramolecular level will be important to solution-process this type of H-bonding π-conjugated molecules for a variety of applications such as optoelectronic devices.

A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer.

Effectively activating macrophages that can 'eat' cancer cells is challenging. In particular, cancer cells secrete macrophage colony stimulating factor (MCSF), which polarizes tumour-associated macrophages from an antitumour M1 phenotype to a pro-tumourigenic M2 phenotype. Also, cancer cells can express CD47, an 'eat me not' signal that ligates with the signal regulatory protein alpha (SIRPα) receptor on macrophages to prevent phagocytosis. Here, we show that a supramolecular assembly consisting of amphiphiles inhibiting the colony stimulating factor 1 receptor (CSF-1R) and displaying SIRPα-blocking antibodies with a drug-to-antibody ratio of 17,000 can disable both mechanisms. The supramolecule homes onto SIRPα on macrophages, blocking the CD47-SIRPα signalling axis while sustainedly inhibiting CSF-1R. The supramolecule enhances the M2-to-M1 repolarization within the tumour microenvironment, and significantly improves antitumour and antimetastatic efficacies in two aggressive animal models of melanoma and breast cancer, with respect to clinically available small-molecule and biologic inhibitors of CSF-1R signalling. Simultaneously blocking the CD47-SIRPα and MCSF-CSF-1R signalling axes may constitute a promising immunotherapy.