Aspergillus terreus camptothecin-sodium alginate/titanium dioxide nanoparticles as a novel nanocomposite with enhanced compatibility and anticancer efficiency in vivo

Abstract

Background: Camptothecin derivatives are one of the most prescribed anticancer drugs for cancer patients, however, the availability, efficiency, and water solubility are the major challenges that halt the applicability of this drug.

Methods: Biosynthetic potency of camptothecin by Aspergillus terreus, open a new avenue for commercial camptothecin production, due to their short-life span, feasibility of controlled growth conditions, and affordability for higher growth, that fulfill the availability of the scaffold of this drug.

Results: Camptothecin (CPT) was purified from the filtrates of A. terreus, and their purity was checked by HPLC, and its chemical structure was verified by LC/MS, regarding to the authentic one. To improve the anticancer efficiency of A. terreus CPT, the drug was conjugated with sodium alginate (SA)/Titanium dioxide nanoparticles (TiO₂NPs) composites, and their physicochemical properties were assessed. From the FT-IR profile, a numerous hydrogen bond interactions between TiO₂ and SA chains in the SA/TiO₂ nanocomposites, in addition to the spectral changes in the characteristic bands of both SA/TiO₂ and CPT that confirmed their interactions. Transmission electron microscopy analysis reveals the spherical morphology of the developed SA/TiO₂NPs nanocomposite, with the average particle size ~ 13.3 ± 0.35 nm. From the results of zeta potential, successful loading and binding of CPT with SA/TiO₂ nanocomposites were observed.

Conclusion: The in vivo study authenticates the significant improvement of the antitumor activity of CPT upon loading in SA/TiO₂ nanocomposites, with affordable stability of the green synthesized TiO₂NPs with Aloe vera leaves extract.

Keywords: Anticancer efficiency; Camptothecin; Sodium alginate; Titanium dioxide nanoparticles.

Fig. 1

The scheme of green synthesis of TiO₂NPs from the extract of Aloe Vera

Fig. 2

Chromatographic, spectroscopic analysis and chemical conjugation of camptothecin from the filtrates of Aspergillus terreus. After growing of the fungal culture, camptothecin was extracted and purified as described in Materials and Methods. The purity of extracted CPT of A. terreus was checked by HPLC (A), and its chemical structure was resolved from the LC/MS analysis (B). C Scheme of putative chemical conjugation of CPT-sodium alginate-titanium dioxide nanoparticles to form nanocomposite

Fig. 3

FT-IR spectra of TiO₂NPs (a), SA (b), SA/TiO₂ nanocomposite (c), CPT (d) and CPT-SA/TiO₂ nanocomposite (e)

Fig. 4

Transmission electron micrograph of TiO₂NPs (A), SA/TiO₂ nanocomposite (B) and CPT-SA/TiO₂ nanocomposite

Fig. 5

Zeta potential spectrum of TiO₂NPs (A), SA/TiO₂ nanocomposite, and CPT-SA/TiO₂ nanocomposite (C)

Fig. 6

The mean tumor volume as a function of the time post-treatment

Fig. 7

The percentage of surviving animals in the different groups as function of incubation time following tumor implantation

Fig. 8

Histopathological sections of negative control of Ehrlich ascites carcinoma and CPT treated Ehrlich ascites carcinoma at 200 × and 400 × by Olympus BX51 Microscope

Fig. 9

Histopathological sections of SA/TiO₂ nanocomposite treated Ehrlich ascites carcinoma at 200 × and 400 × , showing different degree of necrosis

Fig. 10

Histopathological sections of CPT-SA/TiO₂ treated Ehrlich ascites carcinoma at 200 × and 400 × , showing different degree of necrosis at lower dose and higher dose