Anti-melanoma effect of intratumoral injection of PD-L1-siRNA-loaded phenylboronic acid-modified chitooligosaccharide nanoparticles: a preliminary study / 国际药学研究杂志

ABSTRACT

Objective: To prepare phenylboronic acid-modified chitooligosaccharide(PBA-COS)nanoparticles(PBA-COS/ siPD-L1) loaded with PD-L1-siRNA(siPD-L1) and investigate the properties and in vivo anti -melanoma(B16F10) effect of the nanoparticles in mice. Methods: PBA-COS/siPD-L1 nanoparticles were prepared by the complex coacervation method. The particle size and Zeta potential of nanoparticles were investigated by dynamic light scattering. Agarose gel electrophoresis was used to evaluate the binding capacity of PBA-COS carriers to siRNA. The morphology of nanoparticles was observed by transmission electron microscope. In vitro cell uptake efficiency was analyzed by flow cytometry. The mouse subcutaneous B16F10 melanoma model was used to in- vestigate the in vivo effect of intratumoral injection of the nanoparticles on the tumor growth and metastasis. The apoptosis of tumor cells and the lung metastasis of tumors were analyzed and examined by TUNEL staining and HE staining, respectively. Results: The particle size of the PBA-COS/siPD-L1 nanoparticles was(101.9±1.89)nm and the Zeta potential was(25.6±1.52)mV. The nanoparticles were observed to be spherical under the transmission electron microscope. The nanoparticles were efficiently ingestible by B16F10 cells, and the intratumoral injection of the nanoparticles could inhibit tumor growth and lung metastasis of B16F10 melanoma in vivo in mice by inducing the B16F10 cell apoptosis. Conclusion: The intratumoral injection of PBA-OS/siPD-L1 nanoparticles could significantly inhibit tumor growth(the tumor inhibition rate was 42.4%, P<0.01)and lung metastasis of melanoma in mice.