Inter-micellar dynamics in block copolymer micelles: FRET experiments of macroamphiphile and payload exchange

Abstract

The co-formulation of micelles bearing different targeting groups and different payloads could allow the selective and contemporaneous treatment of various cell types with different drugs. The selectivity of such a system, however, would be compromized if macroamphiphiles and/or payloads would undergo inter-micellar exchange, homogenizing the bio-functionalization and the content of the co-formulated micelles. Here we have investigated the occurrence of exchange phenomena in micelles of poly(propylene sulfide)–poly(ethylene glycol) (PPS–PEG) block copolymers, employing fluorophores (dansyl groups) and quenchers (dabsyl groups) either as terminal groups in macroamphiphiles or as encapsulated hydrophobic payloads. Upon exchange, the increased proximity between dansyl and dabsyl groups would significantly increase the quenching efficiency. Our results showed that even employing a rather hydrophilic block copolymer (PPS 10–PEG 44) no significant macroamphiphile exchange could be detected within 24 h from preparation. The payload exchange was temperature-dependent and could be substantially avoided for days if appropriately low storage temperatures are used. We also present an improved experimental procedure for the synthesis of vinyl sulfone-terminated PEG and PPS–PEG and for the conjugation of these structures with labels or possibly bioactive groups.