Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy

Christopher V. Synatschke, Takahiro Nomoto, Horacio Cabral, Melanie Förtsch, Kazuko Toh, Yu Matsumoto, Kozo Miyazaki, Andreas Hanisch, Felix H. Schacher, Akihiro Kishimura, Nobuhiro Nishiyama, Axel H.E. Müller, Kazunori Kataoka

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1161-1172
Number of pages12
JournalACS nano
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 25 2014
Externally publishedYes

Fingerprint

Photodynamic therapy
Micelles
Polyethylene glycols
glycols
therapy
micelles
ethylene
Tumors
tumors
coronas
drugs
blood circulation
polybutadiene
Terpolymers
lysine
Polybutadienes
Hemodynamics
Phase locked loops
Fluorescent Dyes
Self assembly

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Synatschke, C. V., Nomoto, T., Cabral, H., Förtsch, M., Toh, K., Matsumoto, Y., ... Kataoka, K. (2014). Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy. ACS nano, 8(2), 1161-1172. https://doi.org/10.1021/nn4028294

Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy. / Synatschke, Christopher V.; Nomoto, Takahiro; Cabral, Horacio; Förtsch, Melanie; Toh, Kazuko; Matsumoto, Yu; Miyazaki, Kozo; Hanisch, Andreas; Schacher, Felix H.; Kishimura, Akihiro; Nishiyama, Nobuhiro; Müller, Axel H.E.; Kataoka, Kazunori.

In: ACS nano, Vol. 8, No. 2, 25.02.2014, p. 1161-1172.

Research output: Contribution to journalArticle

Synatschke, CV, Nomoto, T, Cabral, H, Förtsch, M, Toh, K, Matsumoto, Y, Miyazaki, K, Hanisch, A, Schacher, FH, Kishimura, A, Nishiyama, N, Müller, AHE & Kataoka, K 2014, 'Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy', ACS nano, vol. 8, no. 2, pp. 1161-1172. https://doi.org/10.1021/nn4028294
Synatschke CV, Nomoto T, Cabral H, Förtsch M, Toh K, Matsumoto Y et al. Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy. ACS nano. 2014 Feb 25;8(2):1161-1172. https://doi.org/10.1021/nn4028294
Synatschke, Christopher V. ; Nomoto, Takahiro ; Cabral, Horacio ; Förtsch, Melanie ; Toh, Kazuko ; Matsumoto, Yu ; Miyazaki, Kozo ; Hanisch, Andreas ; Schacher, Felix H. ; Kishimura, Akihiro ; Nishiyama, Nobuhiro ; Müller, Axel H.E. ; Kataoka, Kazunori. / Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy. In: ACS nano. 2014 ; Vol. 8, No. 2. pp. 1161-1172.
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