We report on the utilization of mixed diblock copolymer micelles as an integrated multifunctional platform for the cancer cell-targeted delivery of chemotherapeutic drugs and magnetic resonance (MR) imaging contrast enhancement under in vitro and in vivo conditions. Two types of amphiphilic diblock copolymers, PCL-b-P(OEGMA-FA) and PCL-b-P(OEGMA-Gd), consisting of a hydrophobic poly(ε-caprolactone) (PCL) block and a hydrophilic poly(oligo(ethylene glycol) monomethyl ether methacrylate) (POEGMA) block, covalently attached with folic acid (FA) and DOTA-Gd (Gd) moieties, respectively, were synthesized via the combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP), and “click” post-functionalization. Mixed micelles co-assembled from PCL-b-P(OEGMA-FA) and PCL-b-P(OEGMA-Gd) possess hydrophobic PCL cores for loading chemotherapeutic drugs and hydrophilic POEGMA outer coronas functionalized with FA and Gd complexes for synergistic functions of targeted delivery and MR imaging contrast enhancement. As-prepared nanosized mixed micelles are capable of physically encapsulating paclitaxel, a well-known hydrophobic anticancer drug, with a loading content of ∼5.0 w/w%, exhibiting controlled release of up to ∼60% loaded drugs over a duration of ∼130 h. In vitrocell viability assays revealed that drug-free mixed micelles are almost non-cytotoxic up to a concentration of 0.2 g L−1, whereas paclitaxel-loaded ones can effectively kill HeLa cells at the same concentration. In vitro MR imaging experiments indicated dramatically increased T1 relaxivity (26.29 s−1mM−1) for mixed micelles compared to that of small molecule counterpart, alkynyl-DOTA-Gd (3.12 s−1mM−1). Further in vivo MR imaging experiments in rabbits revealed considerably enhanced signal intensity, prominent positive contrast enhancement, improved accumulation and retention, and extended blood circulation duration for FA-labeled mixed micellar nanoparticles within the rabbit liver, as compared to those for FA-free mixed micelles and small molecule alkynyl-DOTA-Gd complex. These preliminary results indicate that the reported mixed micellar nanocarriers possess synergistically integrated functions of cancer-targeted drug delivery and controlled release, and MR imaging contrast enhancement, which augurs well for their potential application as a novel type of theranostic platform.

We report on the utilization of mixed diblock copolymer micelles as an integrated multifunctional platform for the cancer cell-targeted delivery of chemotherapeutic drugs and magnetic resonance (MR) imaging contrast enhancement under in vitro and in vivo conditions. Two types of amphiphilic diblock copolymers, PCL-b-P(OEGMA-FA) and PCL-b-P(OEGMA-Gd), consisting of a hydrophobic poly(ε-caprolactone) (PCL) block and a hydrophilic poly(oligo(ethylene glycol) monomethyl ether methacrylate) (POEGMA) block, covalently attached with folic acid (FA) and DOTA-Gd (Gd) moieties, respectively, were synthesized via the combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP), and “click” post-functionalization. Mixed micelles co-assembled from PCL-b-P(OEGMA-FA) and PCL-b-P(OEGMA-Gd) possess hydrophobic PCL cores for loading chemotherapeutic drugs and hydrophilic POEGMA outer coronas functionalized with FA and Gd complexes for synergistic functions of targeted delivery and MR imaging contrast enhancement. As-prepared nanosized mixed micelles are capable of physically encapsulating paclitaxel, a well-known hydrophobic anticancer drug, with a loading content of ∼5.0 w/w%, exhibiting controlled release of up to ∼60% loaded drugs over a duration of ∼130 h. In vitrocell viability assays revealed that drug-free mixed micelles are almost non-cytotoxic up to a concentration of 0.2 g L−1, whereas paclitaxel-loaded ones can effectively kill HeLa cells at the same concentration. In vitro MR imaging experiments indicated dramatically increased T1 relaxivity (26.29 s−1mM−1) for mixed micelles compared to that of small molecule counterpart, alkynyl-DOTA-Gd (3.12 s−1mM−1). Further in vivo MR imaging experiments in rabbits revealed considerably enhanced signal intensity, prominent positive contrast enhancement, improved accumulation and retention, and extended blood circulation duration for FA-labeled mixed micellar nanoparticles within the rabbit liver, as compared to those for FA-free mixed micelles and small molecule alkynyl-DOTA-Gd complex. These preliminary results indicate that the reported mixed micellar nanocarriers possess synergistically integrated functions of cancer-targeted drug delivery and controlled release, and MR imaging contrast enhancement, which augurs well for their potential application as a novel type of theranostic platform.