Multifunctional Magneto-Fluorescent Nanocarriers for Dual Mode Imaging and Targeted Drug Delivery

Abstract

The authors describe a novel multifunctional magneto-fluorescent MFCSNPs-FA-CHI-5FU nanocarrier that consists of magneto-fluorescent nanoparticles (MFCSNPs) targeted with folic acid (FA), modified with chitosan (CHI), and loaded with a 5-flouoruracil (5-FU) in dual mode imaging and targeted drug delivery. Multifunctional magneto-fluorescent nanocarriers show multicolor emission and superparamagnetic behavior which are advantageous for bioimaging and magnetic resonance (MR) imaging, respectively. In-vitro drug release studies show a pH-activated drug release with 92% of loaded 5-FU released in 30 h and MR imaging exhibiting excellent dose-dependent signal enhancement in T 2-weighted images. This suggests that MFCSNPs-FA-CHI-5FU nanocarriers can be used as T 2-weighted negative contrast agents in cancer diagnosis. In-vitro cytotoxicity and anticancer activity of the synthesized MFCSNPs-FA-CHI-5FU nanocarriers were evaluated on three cancer cell lines having different percentages of folate receptors viz. A375, MCF-7, and HeLa cells. The results show a very sensitive drug targeting response. Confocal laser scanning microscopy imaging (CLSM) displays targeted cellular internalization of MFCSNPs-FA-CHI-5FU nanocarriers in cancer cells. The biocompatibility of MFCSNPs-FA-CHI-5FU nanocarriers was ascertained ex-vivo by hemolysis and serum stability studies. The in vivo biodistribution studies were evaluated by radiolabeling MFCSNPs-FA-CHI-5FU nanocarriers with 99m technetium (99mTc). Thus, the synthesized nanocarriers, a dual mode imaging probe, show great potential in targeted drug delivery to improve the existing cancer theranostics.

Synthesis, Principles, and Properties of Magnetite Nanoparticles for In Vivo Imaging Applications—A Review

“…The use of ligands to decorate SPION surfaces is generally considered, such as transferrin [106] or other specific peptides (TWEAK) [107], to target glioblastoma. However, in general, a variety of tumor cell-specific ligands used to decorate the magnetic nanoparticles are reported in recent literature reports, targeting breast cancer cells (with anti-human epidermal growth factor receptor-2 single-chain antibody fragments) [108], squamous cell carcinoma [109,110], and hepatocellular carcinoma (using single-chain antibodies for the epidermal growth factor receptor) [111]. In this latter report, the tumor proliferation was elegantly inhibited through the targeting of nanomedicine that silenced the PBOV1 (prostate and breast cancer overexpressed gene 1) gene (recognized as promoting hepatocellular carcinoma proliferation).…”

“…In fact, near-infrared fluorescent imaging modality has a relatively good potential for tumor detection along with tissue penetration with less background scattering (compared to conventional fluorescent probes). Thus, combinations with MRI that can provide deeper anatomical information, arise as a very interesting option [108,109,110,113]. Others trends than the combination of MRI with optical imaging are also developed for other diagnosis applications, mainly combining MRI and positron emission tomography (PET) [115], or MRI and X-ray imaging [116,117].…”

Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles

“…The treated cells were washed with PBS before being fixed with 4% paraformaldehyde in PBS for 2 h at room temperature. The cells were then dehydrated in a graded ethanol series (30,50,70, and 98%; 30 min each) before drying in a laminar chamber overnight.…”

“…Attaching FA (blue and green lines), the peaks at 562, 600, and 1022 cm −1 decreased, whereas the peaks at 750-985, 1250, 1445, 1494, and 1560-1650 cm −1 increased ( Figure 6D), which discloses FA on the surface. The most important peaks are those that appeared at 1560-1650 cm −1 which are associated with forming amide I and amide II bands by means of the reaction between the amino groups (-NH2) of FA and carboxylic acid groups (-COOH) of GA [50]. Thus, the carboxylic groups are responsible for interaction with FA.…”

Modulating the Delivery of 5-Fluorouracil to Human Colon Cancer Cells Using Multifunctional Arginine-Coated Manganese Oxide Nanocuboids with MRI Properties

“…Structurally, 5-FU is a pyrimidine analogue that blocks the action of thymidylate synthase and inhibits DNA synthesis, leading to cytotoxicity and cell death. However, its high metabolic rate and short half-life (10–20 min) require continuous administration of high doses to maintain the serum concentration, which results in severe toxicities such as hematological, myelosuppression, neural, and gastrointestinal adverse effects. , In addition, conventional formulations of 5-FU show uncontrolled biodistribution. Uncontrolled biodistribution means the inconsistent or nonspecific circulation of drug molecules after administration into a biological system.…”