Oktay Uzun

Molecular Recognition Induced Self-Assembly of Diblock Copolymers: Microspheres to Vesicles

Random diblock copolymer scaffolds grafted with diamidopyridine (DAP) hydrogen bonding recognition units self-assembled to furnish microspheres when mixed with monoblock copolymers decorated with complementary recognition elements. Through choice of block length, microspheres of various sizes could be produced. The relative length of the two blocks plays a crucial role in determining the formation of aggregates. PEG-b-P(S-co-S(DAP)) diblock copolymer was used to fabricate recognition induced pegylated microspheres, by non-covalent crosslinking with monoblock copolymer functionalized with complementary thymine (Thy) units. These self-assembled microspheres can be efficiently crosslinked via photochemical [2pi(s) + 2pi(s)] cycloaddition with the resultant morphology change into vesicular structures.

Duplex strand formation using alternating copolymers

The regular arrangement of complementary diaminopyridine-thymine (DAP-THY) on alternating copolymers permits cooperative binding events and the effective formation of well-controlled micrometre-scale aggregates.

Replenishable drug depot to combat post-resection cancer recurrence

Local drug presentation made possible by drug-eluting depots has demonstrated benefits in a vast array of diseases, including in cancer, microbial infection and in wound healing. However, locally-eluting depots are single-use systems that cannot be refilled or reused after implantation at inaccessible sites, limiting their clinical utility. New strategies to noninvasively refill drug-eluting depots could dramatically enhance their clinical use. In this report we present a refillable hydrogel depot system based on bioorthogonal click chemistry. The click-modified hydrogel depots capture prodrug refills from the blood and subsequently release active drugs locally in a sustained manner. Capture of the systemically-administered refills serves as an efficient and non-toxic method to repeatedly refill depots. Refillable depots in combination with prodrug refills achieve sustained release at precancerous tumor sites to improve cancer therapy while eliminating systemic side effects. The ability to target tissues without enhanced permeability could allow the use of refillable depots in cancer and many other medical applications.