Fabrication of Conjugated Amphiphilic Triblock Copolymer for Drug Delivery and Fluorescence Cell Imaging

An elegant integration of light-emitting segments into the structure of polymeric delivery systems endows the resulting self-assembled nanovehicles with the diagnostic ability toward an enhanced therapeutic efficiency. A variety of polyfluorene (PF)-based binary delivery systems were designed and developed successfully, but PF-based ternary formulations remain rarely explored, likely due to the synthetic challenge. To develop a universal synthesis strategy toward linear conjugated amphiphilic triblock copolymer for cancer theranostics, herein we focused on the functionalization of the PF terminus for further chain extension and prepared well-defined PF-based amphiphilic triblock copolymers, PF-bpoly(epsilon-caprolactone)-b-poly(oligo(ethylene glycol) monomethyl ether methacrylate) (PF-b-PCL-b-POEGMA), by integrated state-of-the-art polymer chemistry techniques, including Suzuki reaction, ring-opening polymerization, atom transfer radical polymerization, and click coupling. The resulting conjugated amphiphilic triblock copolymers can self-assembe into core-shell-corona (CSC) micelles with PF block constructing the inner hydrophobic core for fluorescent tracking, PCL segment forming the hydrophobic middle shell for drug encapsulation, and POEGMA moiety building the hydrophilic outer corona for particulate stabilization. Interestingly, the CSC micelles with hydrophobic PCL middle layer show a greater drug loading capacity as well as a higher fluorescence quantum yield (Phi) relative to the core-shell micelles self-assembled from the control of PF-b-POEGMA diblock copolymers without PCL sequence due to having more hydrophobic spaces and better separation of PF sequence provided simultaneously by the PCL central block. The efficient cellular uptake of the anticancer drug doxorubicin-loaded CSC micelles together with the in vitro cytotoxicity against the HeLa cells makes the conjugated amphiphilic triblock copolymers developed herein a promising platform for simultaneous cell image and drug delivery, thus offering great potential for cancer theranostics.