Vitamin E-rich Nanoemulsion Enhances the Antitumor Efficacy of Low-Dose Paclitaxel by Driving Th1 Immune Response

Ye, Jun; Dong, Wei; Yang, Yanfang; Hao, Huazhen; Liao, Hengfeng; Wang, Bangyuan; Han, Xue; Jin, Yiqun; Xia, Xuejun; Liu, Yuling

doi:10.1007/s11095-017-2141-3

Cited by 20 publications

(17 citation statements)

References 40 publications

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“…The orthotopic 4T1 murine TNBC model was used to compare the antitumor efficiency of various PTX formulations [ 31 ]. Briefly, female BALB/c mice (6–8 weeks old) were inoculated subcutaneously into the right mammary gland with 100 µL of 4T1 cell suspension (1 × 10 6 4T1 cells).…”

Section: Methodsmentioning

confidence: 99%

Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations

Yang

et al. 2021

J Nanobiotechnol

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Background Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. Results Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. Conclusions The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy. Graphic abstract

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Section: Methodsmentioning

confidence: 99%

Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations

Yang

et al. 2021

J Nanobiotechnol

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“…The entrapment efficiency of baicalein was determined by a minicolumn centrifugation method 25 . The minicolumn filled with Sephadex G50 was loaded with 0.2 mL nanoparticles and centrifuged at 500 rpm for 1 min (LDZ5-2; Beijing Medical Centrifuge Factory, Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Dong

Zhou

et al. 2020

Acta Pharmaceutica Sinica B

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Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

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“…In different mouse models, vitamin E or its analogs [alpha-tocopheryloxyacetic acid (α-TEA) and α-tocopheryl succinate (α-TOS)] have been demonstrated to promote a shift towards a T H 1 response. In fact, vitamin E supplementation can increase the production of T H 1 cytokines following influenza infection in mice (Han et al, 2000), enhance the immune response to a specific antigen and the production of cytokines promoting the cell-mediated T H 1 immune response (Radhakrishnan et al, 2013), and increase the secretion of T H 1 cytokines but decrease the secretion of T H 2 cytokines in RAW264.7 cells of macrophage origin (Ye et al, 2017). The analog α-TEA was shown to increase the production of intratumoral IFN-γ and decrease IL-4 levels in a mouse tumor model (Hahn et al, 2011), stimulate autophagy and enhance cross-priming of CD8 + T cells (Y.…”

Section: Vitaminsmentioning

confidence: 99%

Targeting the tumor immune microenvironment with “nutraceuticals”: From bench to clinical trials

Masuelli

Benvenuto

Focaccetti

et al. 2021

Pharmacology & Therapeutics

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Vitamin E-rich Nanoemulsion Enhances the Antitumor Efficacy of Low-Dose Paclitaxel by Driving Th1 Immune Response

Abstract: Vitamin E-rich nanoemulsion has great potential for the treatment of breast cancers with a low dose of paclitaxel via driving Th1 immune response.

Cited by 20 publications

References 40 publications

Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations

Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Targeting the tumor immune microenvironment with “nutraceuticals”: From bench to clinical trials

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