Drug-Loaded and Superparamagnetic Iron Oxide Nanoparticle Surface-Embedded Amphiphilic Block Copolymer Micelles for Integrated Chemotherapeutic Drug Delivery and MR Imaging

Abstract

We report on the fabrication of organic/inorganic hybrid micelles of amphiphilic block copolymers physically encapsulated with hydrophobic drugs within micellar cores and stably embedded with superparamagnetic iron oxide (SPIO) nanoparticles within hydrophilic coronas, which possess integrated functions of chemotherapeutic drug delivery and magnetic resonance (MR) imaging contrast enhancement. Poly(ε-caprolactone)-b-poly(glycerol monomethacrylate), PCL-b-PGMA, and PCL-b-P(OEGMA-co-FA) amphiphilic block copolymers were synthesized at first by combining ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and post- modification techniques, where OEGMA and FA are oligo(ethylene glycol) monomethyl ether methacrylate and folic acid-bearing moieties, respectively. A model hydrophobic anticancer drug, paclitaxel (PTX), and 4 nm SPIO nanoparticles were then loaded into micellar cores and hydrophilic coronas, respectively, of mixed micelles fabricated from PCL-b-PGMA and PCL-b-P(OEGMA-co-FA) diblock copolymers by taking advantage of the hydrophobicity of micellar cores and strong affinity between 1,2-diol moieties in PGMA and Fe atoms at the surface of SPIO nanoparticles. The controlled and sustained release of PTX from hybrid micelles was achieved, exhibiting a cumulative release of ~61% encapsulated drugs (loading content, 8.5 w/w%) over ~130 h. Compared to that of surfactant-stabilized single SPIO nanoparticles (r(2) = 28.3 s(-1) mM(-1) Fe), the clustering of SPIO nanoparticles within micellar coronas led to considerably enhanced T(2) relaxivity (r(2) = 121.1 s(-1) mM(-1) Fe), suggesting that hybrid micelles can serve as a T(2)-weighted MR imaging contrast enhancer with improved performance. Moreover, preliminary experiments of in vivo MR imaging were also conducted. These results indicate that amphiphilic block copolymer micelles surface embedded with SPIO nanoparticles at the hydrophilic corona can act as a new generation of nanoplatform integrating targeted drug delivery, controlled release, and disease diagnostic functions.

Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment

“…[2,3] Also, they can improve the solubility of poorly water-soluble anticancer drugs by encapsulating them into the hydrophobic reservoirs. [4,5] However, despite their advantages in tumor treatment, there are still obstacles limiting clinical applications such as low tumor targetability and poor stability in vivo. [6] In attempts to surmount the problems of conventional polymeric nanoparticles (PNPs), natural polysaccharides such as chitosan, chondroitin, dextran and hyaluronic acid (HA) have been studied as the drug delivery carrier for tumor treatment because they have the benefits of being biocompatible, biodegradable and non-inflammatory.…”

Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability and Biocompatibility of Superparamagnetic Iron Oxide Nanoparticles

“…From the slope of 1/T2 vs particle concentration curves, we estimated CNA-IONP relaxivities to be 70, 63 and 73/s/mM Fe in water, PBS and cell culture medium, respectively. Previous research showed that IONPs have T2 relaxivities around 30 /s/mM Fe (18, 43, 64). Contrast efficiency was considerably enhanced by CNA-IONPs compared with Citrate-IONPs.…”

Advanced Functional Nanomaterials for Theranostics

“…[90] It has been shown that Gadolinium can be chelated with SPIONs for T1- and T2-weighted contrast MRI and this imaged U87-MG tumors in vivo. [91] SPIONs can also serve as a drug delivery platform for MRI guided therapy [92–96] . Interestingly, besides T2-weighted imaging, some Fe 3 O 4 based SPIONs were developed with T1-weighted contrast.…”