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. 2020 Apr 3;18(1):57.
doi: 10.1186/s12951-020-00612-7.

Preparation, characterization and in vitro-in vivo evaluation of bortezomib supermolecular aggregation nanovehicles

Ming-Yue Chen  1   2   3 , Ze-Kuan Xiao  1   2   3 , Xue-Ping Lei  1   2   3 , Jie-Xia Li  1   2   3 , Xi-Yong Yu  1   2   3 , Jian-Ye Zhang  1   2   3 , Guo-Dong Ye  1   2   3 , Yu-Juan Guo  1   2   3 , Guangquan Mo  1   2   3 , Chu-Wen Li  1   2   3 , Yu Zhang  1   2   3 , Ling-Min Zhang  4   5   6 , Zhi-Qiang Lin  7 , Ji-Jun Fu  8   9   10
Affiliations

Preparation, characterization and in vitro-in vivo evaluation of bortezomib supermolecular aggregation nanovehicles

Ming-Yue Chen et al. J Nanobiotechnology. .

Abstract

Backgrounds: Intolerable toxicity and unsatisfactory therapeutic effects are still big problems retarding the use of chemotherapy against cancer. Nano-drug delivery system promised a lot in increasing the patients' compliance and therapeutic efficacy. As a unique nano-carrier, supermolecular aggregation nanovehicle has attracted increasing interests due to the following advantages: announcing drug loading efficacy, pronouncing in vivo performance and simplified production process.

Methods: In this study, the supermolecular aggregation nanovehicle of bortezomib (BTZ) was prepared to treat breast cancer.

Results: Although many supermolecular nanovehicles are inclined to disintegrate due to the weak intermolecular interactions among the components, the BTZ supermolecules are satisfying stable. To shed light on the reasons behind this, the forces driving the formation of the nanovehicles were detailed investigated. In other words, the interactions among BTZ and other two components were studied to characterize the nanovehicles and ensure its stability.

Conclusions: Due to the promising tumor targeting ability of the BTZ nanovehicles, the supermolecule displayed promising tumor curing effects and negligible systemic toxicity.

Keywords: Bortezomib (BTZ); Intermolecular interactions; Supermolecular nanovehicles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
a The particle size of BTZ-NP measured by dynamic light scattering method; b The surface zeta potential of BTZ-NP; c The particle size of BTZ-NP in saline during its storage at room temperature; d TEM images of the BTZ-NP (the scale bar represents 100 nm); e SEM images of the BTZ-NP (the scale bar represents 100 nm); f The drug release profiles of BTZ-NP in phosphate buffer solution; g and h The hemolysis pictures of BTZ-NP and the quantitative results
Fig. 2
Fig. 2
a1H-NMR spectra of BTZ, TA, PVP and the supermolecule BTZ-NP; b FTIR spectra of BTZ, TA, PVP and the supermolecule BTZ-NP; c The isothermal titration calorimetry profile of the TA in the titration syringe and the PVP in the sample cell; d The structure of the BTZ-NP supermolecular nanovehicles
Fig. 3
Fig. 3
a The BTZ-NP uptake by the 4T1 cells; b The viability curves of 4T1 cells after incubation with BTZ-NP or free BTZ for 24 h, measured by MTT method; c The 4T1 cell apoptosis detected by TEM (the scale bar represents 200 nm); d The live/dead assay of 4T1 cells exposed to PBS, BTZ-NP or free BTZ, measured by Calcein/PI; e The caspase 3 expression in 4T1 cells exposed to PBS, BTZ-NP or free BTZ, measured by the GreenNuc kit
Fig. 4
Fig. 4
a The distribution of DiR labelled BTZ-NP in tumor bearing mouse measured by near-infrared fluorescence imaging (the black circle indicates the tumor tissue); b The ICP-MS results of the boron element distribution in the main organs and the tumors (* indicates statistically different, p < 0.05); c The tumor growth profiles (* indicates statistically different, p < 0.05); d The statistic results of the tumor weights at the end of the experiment (* indicates statistically different, p < 0.05); e The body weight curves; f The picture of the tumor tissues at the end of the experiment (the circle implies no tumor tissue observed); g IHC staining of the tumor tissues (the scale bar represents 50 µm)
See this image and copyright information in PMC

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