Preparation and Properties of Tumor-Targeting MRI Contrast Agent Based on Linear Polylysine Derivatives.

Xuanrong Sun,Zhuomin Xu,Dabu Zhu,Yue Cai

doi:10.3390/molecules24081477

Xuanrong Sun, Zhuomin Xu + Show 2 more

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https://doi.org/10.3390/molecules24081477

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Abstract

We developed a tumor-targeted contrast agent based on linear polylysine (PLL) by conjugating a small molecular imaging agent, fluorescent molecule and targeting agent amino phenylboronic acid onto the amino groups of polylysine, which can specifically target monosaccharide sialic acid residues overexpressing on the surface of tumor cell membranes. Further, 3,4,5,6-Tetrahydrophthalic anhydride (DCA) was attached to the free amino groups of the polylysine to change to a negative charge at physiology pH to lower the cytotoxicity, but it soon regenerated to a positive charge again once reaching the acidic intratumoral environment and therefore increased cell uptake. Laser confocal microscopy images showed that most of the polymeric contrast agents were bound to the cancer cell membrane. Moreover, the tumor targeting contrast agent showed the same magnetic resonance imaging (MRI) contrasting performance in vitro as the small molecule contrast agent used in clinic, which made it a promising tumor-targeting polymeric contrast agent for cancer diagnosis.

Highlights

Cancer can be eradicated by chemotherapy, surgery and other methods in its early stages, but by the time it has metastasized, these methods almost never make a difference [1,2]
Magnetic resonance imaging (MRI), as a safe, rapid and accurate clinical diagnosis method causing no harm to the human body, plays a wide role in tumor diagnosis and treatment [4,5]
Due to a large amount of amine groups in the side chain, polylysine was selected as the backbone of the the contrast contrast agent agent and and was was fully fully utilized utilized to to conjugate conjugate functional functional groups such such as as small small molecule molecule contrast agents (Gd ),), fluorescent fluorescent dye dye (Rhodamine)

Summary

Introduction

Cancer can be eradicated by chemotherapy, surgery and other methods in its early stages, but by the time it has metastasized, these methods almost never make a difference [1,2]. Accurate diagnosis of early tumors can greatly improve the survival rate and quality of life of patients [3]. Magnetic resonance imaging (MRI), as a safe, rapid and accurate clinical diagnosis method causing no harm to the human body, plays a wide role in tumor diagnosis and treatment [4,5]. The application of small molecule gadolinium chelates in clinic has many disadvantages, such as nonspecificity, short survival time in vivo and low mobility [8]. Research on large molecule Gd chelates has become highly sought after

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