Synthesis of manganese-incorporated polycaplactone-poly (glyceryl methacrylate) theranostic smart hybrid polymersomes for efficient colon adenocarcinoma treatment.

ABSTRACT

In the current study, a multifunctional nanoscale vesicular system (polymersome) with the ability to accumulate in the site of action, control drug release and integrate diagnostic and therapeutic functions was developed. The theranostic polymersome was engineered as a promising dual-functional nanoplatform, which can be used for tumor therapy and magnetic resonance imaging (MRI). In this regard, the amphiphilic diblock copolymer of poly(ε-caprolactone)-block-poly(glyceryl methacrylate)[(PCL-b-PGMA)] was synthesized by combined ring-opening polymerization (ROP), and reversible addition-fragmentation chain-transfer (RAFT) polymerization techniques followed by hydrolysis of the pendant oxiran rings to hydroxyl groups. Because of the amphiphilic properties and desirable hydrophobic/hydrophilic balance of the synthesized copolymer, it could self-assemble to form a polymersomal structure in an aqueous environment (with diameters about 100-145 nm). The hydrophilic anticancer drug, doxorubicin (DOX) and hydrophobic paramagnetic Mn (phenanthroline)2 complex, being well-represented on T1-weighted magnetic resonance imaging (MRI), were encapsulated in the hydrophilic core (33%±2.3 efficiency) and hydrophobic bilayer membrane (100 %efficient) of a polymersome system, respectively to provide PCL-PGMA@Mn(phen)2/DOX NPs. It was found that adding aptamer AS1411 to NPs surfaces enhanced their specificity and selectivity towards colorectal cancer cells expressing nucleolin (HT29 and C26). In vivo evaluation after intravenous administration of the prepared platform was performed using subcutaneous C26 tumor-bearing Balb/C mice. The obtained results demonstrated that the prepared targeted platform provided a reduced systemic toxicity in terms of body weight loss and mortality while showing efficient tumor regression. Furthermore, the prepared theranostic platform afforded MRI imaging capability for tumor monitoring. It could be concluded that the biocompatible PCL-PGMA magnetic DOX-loaded polymersomes could serve as a versatile multifunctional system for simultaneous tumor imaging and therapy.