Background: We previously developed cabazitaxel (CTX)-loaded human serum albumin nanoparticles (NPs-CTX) via a self-assembly method, and these NPs showed efficacy in prostate cancer therapy. Many studies have shown that the levels of folic acid (FA) receptor on the surface of various tumor cells are high. Therefore, FA-modified NPs-CTX may have enhanced antitumor effects compared with unmodified NPs-CTX. Methods: NPs-CTX were first prepared via self-assembly, and FA was conjugated on the surface of NPs-CTX through the -NH2 groups of the NPs to produce FA-NPs-CTX. The FA-NPs-CTX were evaluated in tumor cells with high FA receptor (FR) expression in vitro and in vivo. Results: Both NPs-CTX and FA-NPs-CTX exhibited good stability and morphology. Drug release from the NPs was not affected by FA conjugation. Compared with CTX dissolved in a mixture of Tween 80 and 13% ethanol (w/w) at a ratio of 1:4 (v/v) (Tween-CTX), the two nanoformulations had lower lytic activity against normal red blood cells. However, FA-NPs-CTX showed greater inhibition of tumor cells with overexpressed FR, compared with NPs-CTX, in the cytotoxicity experiments. Moreover, the cellular uptake of FA-NPs-CTX was enhanced through FR-mediated endocytosis in HeLa cells in vitro and HeLa xenograft tumors in vivo. Although Tween-CTX exhibited tumor growth inhibition similar to FA-NPs-CTX in vivo, this inhibition also caused adverse side effects; the median lethal dose (LD50) of Tween-CTX to mice was 5.68 mg/kg, while FA-NPs-CTX-treated mice survived at doses exceeding 400 mg/kg. Conclusion: The results showed that FA-NPs-CTX caused inhibition of tumor growth in a manner similar to that of Tween-CTX; however, the safety and tolerability of CTX were greatly improved by FA conjugation compared with those of Tween-CTX. In summary, FA-NPs-CTX have great potential in CTX delivery, and this formulation is a promising candidate for the treatment of cancers with high FR levels.

Microfluidic technology (MF) has improved the formulation of nanoparticles (NPs) by achieving uniform particle size distribution, controllable particle size, and consistency. Moreover, because liquid mixing can be precisely controlled in the pores of the microfluidic chip, maintaining high mixing efficiency, MF exerts higher of NP encapsulation efficiency (EE) than conventional methods. MF-NPs-cabazitaxel (CTX) particles (MF-NPs-CTX) were first prepared by encapsulating CTX according to MF. Folate (FA)- Polyethylene glycol (PEG)-NPs-CTX particles (FA-PEG-NPs-CTX) were formulated by connecting FA to MF-NPs-CTX to endow NPs with targeted delivery capability. Accordingly, the mean particle size of FA-PEG-NPs-CTX increased by approximately 25 nm, as compared with MF-NPs-CTX. Upon morphological observation of FA-PEG-NPs-CTX and MF-NPs-CTX by transmission electron microscopy (TEM), all NPs were spherical and particle size distribution was uniform. Moreover, the increased delivery efficiency of CTX in vitro and its strong tumor inhibition in vivo indicated that FA-PEG-NPs-CTX had a powerful tumor-suppressive effect both in vitro and in vivo. In vivo imaging and pharmacokinetic data confirmed that FA-PEG-NPs-CTX had good drug delivery efficiency. Taken together, FA-PEG-NPs-CTX particles prepared using MF showed high efficient and targeted drug delivery and may have a considerable driving effect on the clinical application of targeting albumin NPs.

Cabazitaxel (CTX) is a promising anticancer drug. In this study, CTX-loaded human serum albumin (HSA) nanoparticles (MF-NPs-CTX) were prepared by a microfluidic (MF) method and were evaluated for tumor inhibition in PC-3 and HeLa cells in vitro and in vivo. The in vitro experiments showed that MF-NPs-CTX had higher drug loading content (DLC) as compared with NPs prepared by the bottom-up (BU) method (BU-NPs-CTX). Besides, MF-NPs-CTX exhibited uniform particle size distribution, high stability, sustained drug release, and high biosafety, in vivo imaging studies demonstrated that MF-NPs-CTX accumulated preferentially at the tumor site, compared to BU-NPs-CTX. The enhanced tumor uptake also increased the therapeutic efficacy of MF-NPs-CTX. Both MF-NPs-CTX and tween-CTX exhibited good tumor inhibition effect in vivo. MF-NPs-CTX had better biosafety and biocompatibility than tween-CTX. These results demonstrated that high CTX loading of MF-NPs-CTX has potential in the clinical treatment of tumors.