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Poly(ethylene glycol) Corona Chain Length Controls End-Group-Dependent Cell Interactions of Dendron Micelles.

ABSTRACT: To systematically investigate the relationship among surface charge, PEG chain length, and nano-bio interactions of dendron-based micelles (DMs), a series of PEGylated DMs with various end groups (-NH₂, -Ac, and -COOH) and PEG chain lengths (600 and 2000 g/mol) are prepared and tested in vitro. The DMs with longer PEG chains (DM_2K) do not interact with cells despite their positively charged surfaces. In sharp contrast, the DMs with shorter PEG chains (DM₆₀₀) exhibit charge-dependent cellular interactions, as observed in both in vitro and molecular dynamics (MD) simulation results. Furthermore, all DMs with different charges display enhanced stability for hydrophobic dye encapsulation compared to conventional linear-block copolymer-based micelles, by allowing only a minimal leakage of the dye in vitro. Our results demonstrate the critical roles of the PEG chain length and polymeric architecture on the terminal charge effect and the stability of micelles, which provides an important design cue for polymeric micelles.

SUBMITTER: Hsu HJ

PROVIDER: S-EPMC4334293 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Poly(ethylene glycol) Corona Chain Length Controls End-Group-Dependent Cell Interactions of Dendron Micelles.

Hsu Hao-Jui HJ Sen Soumyo S Pearson Ryan M RM Uddin Sayam S Král Petr P Hong Seungpyo S

Macromolecules 20140930 19

To systematically investigate the relationship among surface charge, PEG chain length, and nano-bio interactions of dendron-based micelles (DMs), a series of PEGylated DMs with various end groups (-NH2, -Ac, and -COOH) and PEG chain lengths (600 and 2000 g/mol) are prepared and tested in vitro. The DMs with longer PEG chains (DM2K) do not interact with cells despite their positively charged surfaces. In sharp contrast, the DMs with shorter PEG chains (DM600</sub ...[more]

PMID: 25709141

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Project description:The use of pH-responsive polymeric micelles is a promising approach to afford the targeted, pH-mediated delivery of hydrophobic drugs within the low-pH tumour milieu and intracellular organelles of cancer cells. However, even for a common pH-responsive polymeric micelle system-e.g., those utilising poly(ethylene glycol)-b-poly(2-vinylpyridine) (PEG-b-PVP) diblock copolymers-there is a lack of available data describing the compatibility of hydrophobic drugs, as well as the relationships between copolymer microstructure and drug compatibility. Furthermore, synthesis of the constituent pH-responsive copolymers generally requires complex temperature control or degassing procedures that limit their accessibility. Herein we report the facile synthesis of a series of diblock copolymers via visible-light-mediated photocontrolled reversible addition-fragmentation chain-transfer polymerisation, with a constant PEG block length (90 repeat units (RUs)) and varying PVP block lengths (46-235 RUs). All copolymers exhibited narrow dispersity values (Đ ≤ 1.23) and formed polymeric micelles with low polydispersity index (PDI) values (typically <0.20) at physiological pH (7.4), within a suitable size range for passive tumour targeting (<130 nm). The encapsulation and release of three hydrophobic drugs (cyclin-dependent kinase inhibitor (CDKI)-73, gossypol, and doxorubicin) were investigated in vitro at pH 7.4-4.5 to simulate drug release within the tumour milieu and cancer cell endosome. Marked differences in drug encapsulation and release were observed when the PVP block length was increased from 86 to 235 RUs. With a PVP block length of 235 RUs, the micelles exhibited differing encapsulation and release properties for each drug. Minimal release was observed for doxorubicin (10%, pH 4.5) and CDKI-73 exhibited moderate release (77%, pH 4.5), whereas gossypol exhibited the best combination of encapsulation efficiency (83%) and release (91% pH 4.5) overall. These data demonstrate the drug selectivity of the PVP core, where both the block molecular weight and hydrophobicity of the core (and accordingly the hydrophobicity of the drug) have a significant effect on drug encapsulation and release. These systems remain a promising means of achieving targeted, pH-responsive drug delivery-albeit for select, compatible hydrophobic drugs-which warrants their further investigation to develop and evaluate clinically relevant micelle systems.

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Dataset Information

Poly(ethylene glycol) Corona Chain Length Controls End-Group-Dependent Cell Interactions of Dendron Micelles.

Publications

Poly(ethylene glycol) Corona Chain Length Controls End-Group-Dependent Cell Interactions of Dendron Micelles.

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