Nanomedicine (London, England) · 2026
Fluorescently labeled Angiopep-2-conjugated-PAMAM nanoparticles to evaluate drug brain-targeted delivery performance.
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Li Xingyue, Wang Jianxiang, Wang Yifei, Hu Fangfang, Yang Xin, Zhang Jingjing, Dong Haiyan, Lu Wen
Аннотация
AIM: To develop and characterize a targeted nano drug delivery system (nano-DDS), specifically fluorescently labeled Angiopep-2-conjugated PAMAM nanoparticles (FITC-APP NPs), and to evaluate its targeting efficiency and therapeutic potential both in vitro and in vivo.
MATERIALS AND METHODS: Angiopep-2 was chemically conjugated to PAMAM via MAL-PEG-NHS crosslinking chemistry, followed by covalent attachment of fluorescein isothiocyanate (FITC) to yield FITC-APP NPs. Using brain microvascular endothelial cells (BMEC), glioma cells (C6 cells), and HEK-293 cells as a negative control, cell adhesion, uptake, and transport behavior were assessed. The cytotoxicity and antitumor efficacy against C6 cells were evaluated comparatively with non-targeted FITC-PAMAM NPs.
RESULTS: FITC-APP NPs exhibited an average hydrodynamic diameter of 32.23 ± 0.62 nm and a zeta potential of -4.36 ± 0.10 mV. Compared with non-targeted FITC-PAMAM NPs, FITC-APP NPs demonstrated significantly higher adhesion, uptake, and transport rates in BMEC and C6 cells, whereas no significant differences were observed in HEK-293 cells. Furthermore, FITC-APP NPs exerted stronger inhibitory effects on C6 cells and displayed enhanced antitumor activity in animal models relative to FITC-PAMAM NPs.
CONCLUSION: These results not only provided data support for the targeting characteristics of FITC-APP NPs, but also provided a method reference for the targeting performance assessment of brain-targeted nano-DDS.
MATERIALS AND METHODS: Angiopep-2 was chemically conjugated to PAMAM via MAL-PEG-NHS crosslinking chemistry, followed by covalent attachment of fluorescein isothiocyanate (FITC) to yield FITC-APP NPs. Using brain microvascular endothelial cells (BMEC), glioma cells (C6 cells), and HEK-293 cells as a negative control, cell adhesion, uptake, and transport behavior were assessed. The cytotoxicity and antitumor efficacy against C6 cells were evaluated comparatively with non-targeted FITC-PAMAM NPs.
RESULTS: FITC-APP NPs exhibited an average hydrodynamic diameter of 32.23 ± 0.62 nm and a zeta potential of -4.36 ± 0.10 mV. Compared with non-targeted FITC-PAMAM NPs, FITC-APP NPs demonstrated significantly higher adhesion, uptake, and transport rates in BMEC and C6 cells, whereas no significant differences were observed in HEK-293 cells. Furthermore, FITC-APP NPs exerted stronger inhibitory effects on C6 cells and displayed enhanced antitumor activity in animal models relative to FITC-PAMAM NPs.
CONCLUSION: These results not only provided data support for the targeting characteristics of FITC-APP NPs, but also provided a method reference for the targeting performance assessment of brain-targeted nano-DDS.