Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy

TLDR: The cytotoxicity profile on cancer cell line and in vitro drug uptake were evaluated both with and without an external magnetic field used as targeting agent and uptake promoter, displaying that magnetic targeting implies advantageous therapeutic effects, that is amplified drug uptake and increased anticancer activity throughout the tumor mass.

About: This article is published in European Journal of Pharmaceutics and Biopharmaceutics.The article was published on 2014-11-01 and is currently open access. It has received 53 citations till now. The article focuses on the topics: Nanocarriers & Drug delivery.

Figures

Fig. 1 - SEM images of IC-SPIONs.

Fig. 5. - Cell viability % (MTS assay) on colon cancer cells (HCT116) of: doxorubicin hydrochloride (a), IC-SPIONs (b), DoxoIC-SPIONs (c) and all the samples previously mentioned in the presence and in the absence of the external magnet (d). Incubation times was 24 and 48 h. The results are reported as the mean ± SD (n = 6). ∗p = 0.0016, ∗∗p = 0.00018.

Table 1. Molar derivatization degree values of EDA, Sq and PEG linked to inulin and molecular weight (Mw) and dispersity of the correspondent copolymers.

Fig. 4. - Drug release of Doxo-IC-SPIONs and doxorubicin hydrochloride in PBS solution at pH 7.4 (a) and at pH 5.5 (b).

Fig. 3. - Photographs of IC-SPIONs water dispersion before (a) during (b) and after (c) the application of an external magnetic field overnight. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Table 2. - DLS data and zeta potential values of IC-SPIONs and Doxo-IC-SPIONs samples in aqueous medium at a final copolymer concentration of 0.2 mg/mL.

Frequently asked questions

Q1. What are the contributions in "Inulin-based polymer coated spions as potential drug delivery systems for targeted cancer therapy" ?

This paper deal with the synthesis and characterization of PEGylated squalene-grafted-inulin amphiphile capable of self-assembling and self-organizing into nanocarriers once placed in aqueous media. Inulin was firstly modified in the side chain with primary amine groups, followed in turn by conjugation with squalenoyl derivatives through common amidic coupling agents and PEGylation by imine linkage. The system was characterized in terms of hydrodynamic radius, zeta potential, shape and drug loading capacity. 

Q2. What was the zeta potential of the IC-SPIONs?

It was found that the IC-SPIONs possessed positively charged surfaces with values of zeta potential of 21 ± 8 mV, probably due to the presence of protonated amines onto the nanoparticle surface. 

Q3. What is the role of doxorubicin in the drug delivery system?

Doxorubicin was used as anticancer drug model because it is also endowed with fluorescence properties, which can be exploited to evaluate its uptake into cells by means of fluorescence microscopy. 

Q4. What was the effect of the doxorubicin loading on the nanoparticles?

Being hydrophobic interactions concentration dependent phenomena, during the first step nanoparticles had available a large number of doxorubicin molecules which gave rise to compacted nanoparticles with high drug payload. 

Q5. How many IC-SPIONs were incubated for 24 h?

In particular, IC-SPIONs at concentration of 0.27 mg/mL and Doxo-IC-SPIONs at the same concentration, which corresponds to 50 μM in doxorubicin hydrochloride, were incubated for 24 h and 48 h either in the presence of a magnetic field or not. 

Q6. How long did it react with the solution of 1,1′,2-tris-nor?

It was then added at 0 °C within 20 min to the solution of 1,1′,2-tris-nor-squalene aldehyde, previously prepared, and left to react for 2 h at 0 °C with stirring. 

Q7. What is the effect of the IC-SPIONs on HCT116 cells?

the cytotoxic effect on HCT116 cells increases by about 50% when cells were incubated with Doxo-IC-SPIONs for 24 h in the presence of the external magnet, while the effectiveness was lower if compared with the same dose of free doxorubicin hydrochloride. 

Q8. What is the purpose of this paper?

This paper deal with the synthesis and characterization of PEGylated squalene-grafted-inulin amphiphile capable of self-assembling and self-organizing into nanocarriers once placed in aqueous media. 

Q9. What is the stoichiometric condition used to convert the SqCOOH?

The stoichiometric conditions employed (moles of SqCOOH-C27/moles of amino pendant groups in INU-EDA = 0.1; moles of EDC-HCl/moles of SqCOOH-C27 = 1.2 and moles of NHS/moles of SqCOOH-C27 = 1.2) were fixed to obtain a quantitative conversion of the SqCOOHC27 carboxylic functions to amide. 

Q10. What is the molar derivatization degree of the INU-Sq-?

INU-Sq-PEG2000 copolymer was characterized by means of 1H NMR spectroscopy, which confirmed the introduction of PEG2000 chains on the INU-Sq backbone and allowed the calculation of the molar derivatization degree (DDPEG%). 

Q11. What is the effect of the external magnet on cells?

It is interesting to note that, in agreement with the cytotoxicity results above reported, the number of cells incubated with the external magnet appeared drastically reduced after 48 h of incubation (see line C of Fig. 6c), endorsing the hypothesis that the presence of the external magnetic force improves nanoparticles uptake. 

Q12. How did the squalenoyl derivative get its synthesis?

This copolymer was easily obtained by in turn conjugating squalenoyl derivative and semitelechelic aldehyde terminated PEG chains of average weight molecular weight 2000, without employing drastic synthetic conditions.