Folic Acid-Adorned Curcumin-Loaded Iron Oxide Nanoparticles for Cervical Cancer

Abstract

Cancer is a deadly disease that has long plagued humans and has become more prevalent in recent years. The common treatment modalities for this disease have always faced many problems and complications, and this has led to the discovery of strategies for cancer diagnosis and treatment. The use of magnetic nanoparticles in the past two decades has had a significant impact on this. One of the objectives of the present study is to introduce the special properties of these nanoparticles and how they are structured to load and transport drugs to tumors. In this study, iron oxide (Fe₃O₄) nanoparticles with 6 nm sizes were coated with hyperbranched polyglycerol (HPG) and folic acid (FA). The functionalized nanoparticles (10-20 nm) were less likely to aggregate compared to non-functionalized nanoparticles. HPG@Fe₃O₄ and FA@HPG@Fe₃O₄ nanoparticles were compared in drug loading procedures with curcumin. HPG@Fe₃O₄ and FA@HPG@Fe₃O₄ nanoparticles' maximal drug-loading capacities were determined to be 82 and 88%, respectively. HeLa cells and mouse L929 fibroblasts treated with nanoparticles took up more FA@HPG@Fe₃O₄ nanoparticles than HPG@Fe₃O₄ nanoparticles. The FA@HPG@Fe₃O₄ nanoparticles produced in the current investigation have potential as anticancer drug delivery systems. For the purpose of diagnosis, incubation of HeLa cells with nanoparticles decreased MRI signal enhancement's percentage and the largest alteration was observed after incubation with FA@HPG@Fe₃O₄ nanoparticles.

Keywords: MRI; cervical cancer therapy; curcumin; iron oxide nanoparticles; polyglycerol; targeted delivery.

Figure 1

(A) Synthesis of HPG@Fe₃O₄ and FA@ HPG@Fe₃O₄ nanoparticles. (B) Schematic illustration of potential applications of folate-targeted for cervical cancer treatment.

Figure 2

SEM and TEM images of (A and C) Fe₃O₄ and (B and D) HPG@Fe₃O₄ nanoparticles. Size distribution analysis of (E) Fe₃O₄ and (F) HPG@Fe₃O₄ nanoparticles.

Figure 3

(A) FT-IR test results of HPG-coated nanoparticles treated with 5, 25, and 50% (top trace) folic acid. (B) TGA curves for Fe₃O₄ and HPG@Fe₃O₄ nanoparticles.

Figure 4

(A) Diagram of loading efficiency for encapsulation of curcumin on 5, 25, and 50% folic acid-coated nanoparticles. (B) In vitro release curve of curcumin release from polyglycerol-coated nanoparticles and 5, 25, and 50% folic acid-targeted nanoparticles.

Figure 5

HeLa cell line’s optical microscopy images related to (A) before and (B) after MTT treatment. L929 cell line’s optical microscopy images related to (C) before and after (D) MTT. The scale bar is 50 μm.

Figure 6

Viability of HeLa cells after exposure to nanoparticles for (A) 24, (B) 48, and (C) 72 h treatment times. Nanoparticles exert their cytotoxicity in a time- and concentration-dependent manner to reduce viability of cancer cells. The lowest viability is observed after 72 h and exposure to HGP@Fe₃O₄ nanoparticles.

Figure 7

Toxicity evaluation of nanoparticles on L929 fibroblasts as normal cells after (A) 24, (B) 48, and (C) 72 h treatment times. Based on the results, they demonstrate partial toxicity toward normal cells and their overall biocompatibility is promising.

Figure 8

FA@HPG@Fe₃O₄ uptake through HeLa cells. (A–C) Cellular uptake of nanoparticles by HeLa cells. (D) Schematic representation of FA-adorned HPG IONPs in internalizing in cells and release of curcumin for cervical cancer therapy.

Figure 9

(A) T2-weighted MRI phantom images of HeLa cells after incubation with nanocarriers at a concentration of 0.2 mg/mL (a, left) FA@HPG@Fe₃O₄ (25% w: w FA:polymer), (b) HPG@Fe₃O₄, (c) control sample, (d, right) Fe₃O₄ nanoparticles. (B) Signal intensity and increase in in vitro T2-weighted MRI.