A new strategy to enhance targeting properties of polymeric nanoparticles

Nanoparticles (NPs) made up of amphiphilic block copolymers have attracted significant attention in the field of innovative anticancer therapies. The most common approach to improve selectively their accumulation in tumor tissues remains surface decoration with target moieties recognizing specific receptors that are over-expressed on cancer cells. The purpose of this work is to improve the targeting ability of NPs (Figure 1) prepared by self-assembling of copolymers based on poly(ethylene glycol) (PEG) as the hydrophilic block and poly(?-caprolactone) (PCL) as the hydrophobic one. Initial tailoring of PEG is performed through a method that allows selective introduction of target molecules at only one end [1]. A new strategy is developing, through synthesis of a polyrotaxane [2]. A polyrotaxane (Figure 2) is an interlocked molecular architecture consisting of a polymer, macrocycles as cyclodextrins (CDs), and stoppers, i.e., molecules with steric hindrance that do not allow CDs to get off. ?-CDs locked in the PEG block imparts a more organized (brush-like) conformation to chains and, as a consequence, should make molecules on the surface more accessible. The adopted strategy consists in synthesizing a polyrotaxane bearing ?-CDs only on PEG block. The polyrotaxane copolymer was characterized through FTIR, 1HNMR, 13CNMR and DOSY spectroscopy, TGA and DSC thermal analysis, and gel permeation chromatography (GPC). In particular, GPC confirms the copolymer conformation through the Mark-Houwink ? coefficient.