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Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy

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Abstract

In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ±2.16) nm]#1 with a homogeneous distribution and high encapsulation efficiency (80.06 ±0.19)%. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.

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... Importantly, the same outcomes were not observed when either vitamin B 12 or folate were used as targeting agents [23,24]. Therefore, biotin has emerged as a remarkable active targeting ligand for nanocarriers [25][26][27][28][29]. Biotin has a valeric acid tail, through which it can be conjugated to other molecules to achieve biotinylation (Scheme 1A) [30]. ...
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... 8,9 Photodynamic therapy (PDT) is a method of joint use of light and special drugs (photosensitizers) for the treatment of diseased cells and tissue therapy. 10 The application of TiO 2 NPs in the field of antitumor therapy has aroused widespread concern. The field of molecular imaging has been gaining interest in the research world. ...
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