Enhanced transcytosis and therapeutic efficacy of paclitaxel nanoparticles: Pyridylboronic acid modification and sialic acid targeting

Efficient drug delivery and deeper penetration into tumors have become a primary focus of anti-tumor nanomedicine. In this study, pyridylboronic acid (BPA), as a targeting ligand for sialic acid, which is highly expressed on the surface of tumor cells, was conjugated with DSPE-PEG2k-NH₂ to synthesize DSPE-PEG2k-BPA and used to encapsulate PTX. The resultant PTX@DSPE-PEG2k-BPA nanoparticles (DPB NPs) showed a mean particle size of 189.0 ± 3.5 nm, with a high drug loading content of 48.75 % and a rod-like morphology. In contrast to PTX@DSPE-mPEG2k nanoparticles (DP NPs), DPB NPs displayed enhanced cellular uptake and targetability to 4T1 tumor cells. Interestingly, BPA modification could also enhance transcytosis through the endoplasmic reticulum-Golgi pathway, thus improving penetration and accumulation of nanoparticles in tumors. An in vivo study on 4T1 tumor-bearing mice demonstrated that DPB NPs achieved a faster and more accumulation in tumors than DP NPs after intravenous administration, led to significantly improved therapeutic efficacy with a higher tumor inhibition rate (74.27 % vs 50.58 %, p < 0.01). In conclusion, the modification of BPA presents a strategy for the development of drug delivery systems that exhibit dual functionalities: active targeting and transcytosis.