Evaluation of the Antitumor Effect and Immune Response of Micelles Modified with a Polysialic Acid-d-α-Tocopheryl Polyethylene Glycol 1000 Succinate Conjugate
- 18 August 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in AAPS PharmSciTech
- Vol. 22 (7), 1-14
- https://doi.org/10.1208/s12249-021-02047-1
Abstract
D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) has shown potential applications in cancer therapy owing to its attractive properties, including reversal of multi-drug resistance and synergistic effects with antitumor drugs. However, its associated shortcomings cannot be underestimated, including activation of the body’s immune response and acceleration of blood clearance of polyethylene glycolylated preparations. Polysialic acid (PSA) is a polysaccharide homopolymer, with the dual function of immune camouflage and tumor targeting. PSA and TPGS conjugates (PSA-TPGS) were synthesized to weaken the immune risks of TPGS. We developed PSA-TPGS and TPGS self-assembled mixed micelles and encapsulated the classical antineoplastic, docetaxel. The particle size of docetaxel-loaded mixed micelles was 16.3 ± 2.0 nm, with entrapment efficiency of 99.0 ± 0.9% and drug-loading efficiency of 3.20 ± 0.03%. Antitumor activity studies revealed that the mixed micelles showed better tumor inhibition than Tween 80 and TPGS micelles. Detection of the accelerated blood clearance (ABC) phenomenon demonstrated that insertion of PSA-TPGS into the micelles weakened the ABC phenomenon induced by TPGS. In summary, PSA-TPGS could be a potential nanocarrier to improve antitumor activity and weaken immune responses. Graphical abstractKeywords
This publication has 57 references indexed in Scilit:
- Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beaglesInternational Journal of Nanomedicine, 2012
- Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal modelsNanoscale Research Letters, 2011
- Biocompatibility of hydrophilic silica-coated CdTe quantum dots and magnetic nanoparticlesNanoscale Research Letters, 2011
- Anti-PEG IgM Response against PEGylated Liposomes in Mice and RatsPharmaceutics, 2010
- A novel size-tunable nanocarrier system for targeted anticancer drug deliveryJournal of Controlled Release, 2010
- Vitamin E succinate induced apoptosis and enhanced chemosensitivity to paclitaxel in human bladder cancer cells in vitro and in vivoCancer Science, 2009
- Tumor-associated macrophages (TAM) as major players of the cancer-related inflammationJournal of Leukocyte Biology, 2009
- Role of tumor-associated macrophages in tumor progression and invasionCancer and Metastasis Reviews, 2006
- Inflammation and cancerNature, 2002
- The role of tumour‐associated macrophages in tumour progression: implications for new anticancer therapiesThe Journal of Pathology, 2002