Multicompartment Micelles with Adjustable Poly(ethylene glycol) Shell for Efficient in Vivo Photodynamic Therapy

Abstract

We describe the preparation of well-defined multicompartment micelles from polybutadiene-block-poly(1-methyl-2-vinyl pyridinium methyl sulfate)-block-poly(methacrylic acid) (BVqMAA) triblock terpolymers and their use as advanced drug delivery systems for photodynamic therapy (PDT). A porphyrazine derivative was incorporated into the hydrophobic core during self-assembly and served as a model drug and fluorescent probe at the same time. The initial micellar corona is formed by negatively charged PMAA and could be gradually changed to poly(ethylene glycol) (PEG) in a controlled fashion through interpolyelectrolyte complex formation of PMAA with positively charged poly(ethylene glycol)-block-poly(L-lysine) (PLL-b-PEG) diblock copolymers. At high degrees of PEGylation, a compartmentalized micellar corona was observed, with a stable bottlebrush-on-sphere morphology as demonstrated by cryo-TEM measurements. By in vitro cellular experiments, we confirmed that the porphyrazine-loaded micelles were PDT-active against A549 cells. The corona composition strongly influenced their in vitro PDT activity, which decreased with increasing PEGylation, correlating with the cellular uptake of the micelles. Also, a PEGylation-dependent influence on the in vivo blood circulation and tumor accumulation was found. Fully PEGylated micelles were detected for up to 24 h in the bloodstream and accumulated in solid subcutaneous A549 tumors, while non- or only partially PEGylated micelles were rapidly cleared and did not accumulate in tumor tissue. Efficient tumor growth suppression was shown for fully PEGylated micelles up to 20 days, demonstrating PDT efficacy in vivo.

Giant tubular and toroidal vesicles from self-assembled triblock copolymer–polyaniline complexes in water

“…The additives range from small molecules to block copolymers through metal ions and homopolymers [14][15][16] . As the result of complexation of flexible chain block copolymer and homopolymer additives, complex morphologies such as compartmentalized micellar shells and cores has been reported in previous studies 14 .…”

Polymeric Nanostructures for Imaging and Therapy

“…(B) Complexation with PLL- b -PEG diblock copolymers and subsequent crosslinking of PMAA with PLL yields PEGylated micelles (BVqMAA/PLL- b -PEG). Reprinted with permission from Reference 272. Copyright 2014 American Chemical Society.…”

Biomedical applications of nano-titania in theranostics and photodynamic therapy

“…85,86 For deep tissue penetration, the near infrared (NIR) light range (620-850 nm) is more favored because of the less harmful and maximum penetration properties. This bottleneck develops the concept for hydrophilic nano-PSs, such as micelles, liposomes, low density lipoproteins, [102][103][104][105] etc. 88 Photosensitive nanocomposites like TiO 2 nanoparticles could be administered systemically to the living tissue and upon attaining a certain concentration in the desired location, visible light or NIR light is passed through the subject tissue.…”