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. 2016 Jul 26:11:3451-9.
doi: 10.2147/IJN.S105420. eCollection 2016.

Cabazitaxel-loaded human serum albumin nanoparticles as a therapeutic agent against prostate cancer

Na Qu  1 , Robert J Lee  2 , Yating Sun  1 , Guangsheng Cai  1 , Junyang Wang  1 , Mengqiao Wang  1 , Jiahui Lu  1 , Qingfan Meng  1 , Lirong Teng  1 , Di Wang  1 , Lesheng Teng  3
Affiliations

Cabazitaxel-loaded human serum albumin nanoparticles as a therapeutic agent against prostate cancer

Na Qu et al. Int J Nanomedicine. .

Abstract

Cabazitaxel-loaded human serum albumin nanoparticles (Cbz-NPs) were synthesized to overcome vehicle-related toxicity of current clinical formulation of the drug based on Tween-80 (Cbz-Tween). A salting-out method was used for NP synthesis that avoids the use of chlorinated organic solvent and is simpler compared to the methods based on emulsion-solvent evaporation. Cbz-NPs had a narrow particle size distribution, suitable drug loading content (4.9%), and superior blood biocompatibility based on in vitro hemolysis assay. Blood circulation, tumor uptake, and antitumor activity of Cbz-NPs were assessed in prostatic cancer xenograft-bearing nude mice. Cbz-NPs exhibited prolonged blood circulation and greater accumulation of Cbz in tumors along with reduced toxicity compared to Cbz-Tween. Moreover, hematoxylin and eosin histopathological staining of organs revealed consistent results. The levels of blood urea nitrogen and serum creatinine in drug-treated mice showed that Cbz-NPs were less toxic than Cbz-Tween to the kidneys. In conclusion, Cbz-NPs provide a promising therapeutic for prostate cancer.

Keywords: cabazitaxel; drug delivery; human serum albumin; nanoparticle; prostate cancer; toxicity.

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Figures

Figure 1
Figure 1
Physicochemical characterization of Cbz-NPs. Notes: (A) A schematic diagram of Cbz-NPs preparation. (B) Lyophilized NPs. (C) NPs redissolved in saline. (D) SEM image of Cbz-NPs. Abbreviations: Cbz-NPs, cabazitaxel-loaded human serum albumin nanoparticles; HSA, human serum albumin; SEM, scanning electron microscopy.
Figure 2
Figure 2
In vitro hemolysis assay of Cbz-Tween and Cbz-NPs. Notes: (A) HR (%) of various concentration of Cbz. (B) Images of RBCs treated with Cbz-Tween or Cbz-NPs. Data are expressed as mean ± SE (n=3). **P<0.01; ***P<0.001. Abbreviations: Cbz-NPs, cabazitaxel-loaded human serum albumin nanoparticles; HR (%), hemolysis ratio; RBC, red blood cells; SE, standard error.
Figure 3
Figure 3
The mean plasma concentration–time profiles for Cbz. Notes: (A) The concentration–time curve of Cbz in rat plasma after Cbz-NPs and Cbz-Tween administration. (B) The subtle differences at early time points are shown as an inset. Abbreviations: Cbz-NPs, cabazitaxel-loaded human serum albumin nanoparticles; h, hours.
Figure 4
Figure 4
Tissue distribution of Cbz to the organs after treatments with either Cbz-NPs or Cbz-Tween. Notes: (A) Heart, (B) liver, (C) spleen, (D) lung, (E) kidney, and (F) tumor. Data are expressed as mean ± SE (n=6). **P<0.01. Abbreviations: Cbz-NPs, cabazitaxel-loaded human serum albumin nanoparticles; h, hours; SE, standard error.
Figure 5
Figure 5
Antitumor activity of Cbz-NPs treatment on prostate cancer tumor-bearing mice compared to Cbz-Tween treatment. Notes: (A) Body weight of the mice during the experiment. (B) Antitumor effect of Cbz-NPs and Cbz-Tween tumor-bearing mice. (C) Images of the nude mice after intravenous injections of Cbz-Tween and Cbz-NPs, saline was used as a control. Data are expressed as mean ± SE (n=7). **P<0.01; ***P<0.001. Abbreviations: Cbz-NPs, cabazitaxel-loaded human serum albumin nanoparticles; SE, standard error.
Figure 6
Figure 6
The pathological hematoxylin and eosin staining analysis of tissue sections. Note: Arrows were used to indicate relevant areas of fat liver and spleen infiltration. Abbreviation: Cbz-NPs, cabazitaxel-loaded human serum albumin nanoparticles.
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