Folate receptor-targeted fluorescent paramagnetic bimodal liposomes for tumor imaging

Abstract

Rationale and objective: Receptor-targeted delivery of imaging and therapeutic agents can lead to enhanced efficacy for both. Multimodality imaging offers unique advantages over traditional single modality imaging. Tumor marker folate receptor (FR)-targeted fluorescent paramagnetic bimodal liposomes were synthesized to co-deliver paramagnetic and fluorescence agents for magnetic resonance (MR) and optical bimodal imaging contrast enhancement. Materials and methods: Fluorescent and paramagnetic bimodal liposomes were synthesized with a mean diameter of 136 nm and a low polydispersity index. The liposomes incorporated folate-PEG 3350 -CHEMS for FR targeting, Gd(III)[N,N-Bis-stearylamidomethyl-N'-amidomethyl]diethylenetriamine tetraacetic acid (Gd-DTPA-BSA) for MR contrast, and calcein for fluorescence. To determine the specificity and efficiency of delivery, the liposomes were evaluated in FR-positive KB and HeLa cells and FR-negative A549 cells, which were analyzed by fluorescence microscopy, magnetic resonance imaging (MRI), and flow cytometry (FCM). Results: FR-specific and efficient cellular uptake of the FR-targeted bimodal liposomes was confirmed by fluorescence microscopy and by FCM. The mean fluorescence intensity (MFI) of KB cells treated with FR-targeted liposomes was 45× that of cells treated with nontargeted liposomes, and 18× that of cells treated with FR-targeted liposomes and excess folic acid (FA). The MFI of HeLa cells treated with targeted liposomes was 33× that of nontargeted liposomes, and was 16× that of the mixture of targeted liposomes and free FA. In contrast, the MFI of A549 cells treated with FR-targeted liposomes was nearly the same as those treated with nontargeted liposomes. The T 1 -weighted MR images of HeLa and KB cells incubated with FR-targeted liposomes had much higher signal intensity than those treated with nontargeted liposomes or free Gd-DTPA. Furthermore, the FR-targeting effect could be blocked by excess free FA. Conclusion: FR-targeted fluorescent paramagnetic bimodal liposomes provided a novel platform for bimodal tumor imaging and theranostic delivery.

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

“…Derivatized nanosystems, capable of diagnosis, drug delivery, and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine. 25,26 Interesting results have been obtained by using the BN peptide. 27 The 14-residue BN peptide, its eight-residue C-terminal peptide sequence (BN [7][8][9][10][11][12][13][14]), or other BN analogues acting as antagonists may be used to target BN receptor subtype 2, also known as gastrin releasing peptide receptor (GRPR).…”

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

“…This might be due to easier proton exchange between the bulk water and the Gd in NTLs and GTLs. 25,46 Confocal microscopy and flow cytometry analysis studies…”

“…This may be caused by the hydrophilicity of Gd⋅DTPA, which makes the molecules neither able to enter cells by diffusion nor bind to the cell surface. 25 Thus, Gd⋅DTPA was removed during the washing procedure of the cells, resulting in a relatively low MR signal. The results of axial scan of T 1 -weighted images of cell pellets were in accordance with that of coronal scan.…”

“…When introducing macromolecular carriers, signal enhancement to MRI is improved by shortening the T 1 relaxation time of water protons. 2,[23][24][25] Liposomes are by now one of the most successful nanomedicines, which have been applied to deliver a wide variety of chemical molecules, genes, CAs, and even nanoparticles. 26 Compared with other delivery systems (such as nanoparticles, micelles, and carbon nanotubes), liposomes show superior biocompatibility, biodegradability, relatively low toxicity, and improved control over size and surface functionality.…”

“…Some studies have shown that by anchoring ligands in liposome bilayers, the affinity and specificity of liposomal systems to specific targets could be enhanced. 24,25,29 Among the target-specific ligands, aptamers have appeared as promising candidates. 3,4,30 Therefore, GBI-10-targeted gadolinium-loaded liposomes (GTLs) were designed and prepared as a MRI CA for the diagnosis of tumor for the first time in this original study.…”