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. 2023 Apr 18;15(4):1269.
doi: 10.3390/pharmaceutics15041269.

Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity

Hui Li  1   2 , Wei Qiao  2 , Yizhe Shen  2 , Huashan Xu  2 , Yuan Fan  1   2 , Yuxiang Liu  2 , Yadi Lan  2 , Yan Gong  2 , Fuxue Chen  2 , Shini Feng  2
Affiliations

Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity

Hui Li et al. Pharmaceutics. .

Abstract

Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor.

Keywords: biomimetic; boron nitride; cancer cell membrane; drug delivery; homologous targeting.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The preparation of CM@BN/DOX complexes.
Figure 2
Figure 2
Characterization of CM@BN/DOX. (a) TEM image of boron nitride (BN). (b) TEM image of CM@BN. (c) The protein profiles of the BV2 cell membrane fragments and CM@BN. (d) Hydro-dynamic size of BN, CCM, CM@BN, and CM@BN/DOX. (e) Zeta potentials of BN, CCM, CM@BN, and CM@BN/DOX. (f) XPS spectrum of BN. (g) XPS spectrum of CM@BN. (h) Stability of CM@BN/DOX in PBS (pH = 7.4).
Figure 3
Figure 3
Biocompatibility in vitro. (a) The cytotoxicity of BN and CM@BN on various cell lines using concentrations ranging from 0 to 100 μg/mL for a 24-h period. (b,c) The hemolysis of red blood cells that were incubated with Triton X-100, PBS, BN, and CM@BN/DOX.
Figure 4
Figure 4
Drug loading and release. (a) Amount of doxorubicin (DOX) loaded on BN and CM@BN. (b) DOX release from BN/DOX and CM@BN/DOX complexes at different conditions. Data expressed as means ± SD, *** p < 0.001.
Figure 5
Figure 5
Cellular uptake. (a) Confocal laser scanning microscopy (CLSM) images of BV2 cells co-cultured with free DOX, BN@DOX, and CM@BN/DOX for 2 h. Scale bar = 20 µm. (b) Analysis of free DOX, BN/DOX, and CM@BN/DOX uptake by BV2 cells by flow cytometry (FCM). (c) Quantitative analysis of cellular uptake by FCM. Data are expressed as means ± SD, *** p < 0.001.
Figure 6
Figure 6
Homologous targeting of CM@BN/DOX. (a) Confocal laser scanning microscopy images of BV2, HeLa, GMI-R1, and Ast cells incubated with CM@BN/DOX for 2 h. Scale bar = 20 µm. (b) The intracellular uptake of CM@BN/DOX by BV2, HeLa, GMI-R1, and Ast cells using FCM (blank group was represented as grey). (c) Quantitative analysis. Data are presented as means ± SD, *** p < 0.001.
Figure 7
Figure 7
In vitro antitumor activity. (a) The viability of BV2 cells following treatment with varying concentrations of free DOX, BN/DOX, and CM@BN/DOX by the CCK-8 method. (b) The cytotoxicity of BV2 cells exposed to various treatments (green: living cells; red: dead cells). Scale bar = 100 µm. (c) The impact of varying concentrations of CM@BN/DOX on the cell viability of four different types of cells: BV2, HeLa, GMI-R1, and Ast. (d) The cytotoxicity of BV2, HeLa, GMI-R1, and Ast cells after treatment with CM@BN/DOX. Scale bar = 100 µm. Data are expressed as means ± SD, * p < 0.05, *** p < 0.001.
Figure 8
Figure 8
In vitro antitumor activity. (a,c) Cellular apoptosis of BV2 cells dealt with various reagents by FCM. (b,d) Cellular apoptosis of BV2, HeLa, GMI-R1, and Ast cells treated with CM@BN/DOX by FCM. Data are expressed as means ± SD, *** p < 0.001.
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