Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment

Abstract

The biogenic aliphatic polyamines (spermine, spermidine, and putrescine) are responsible for numerous cell functions, including cell proliferation, the stabilization of nucleic acid conformations, cell division, homeostasis, gene expression, and protein synthesis in living organisms. The change of polyamine concentrations in the urine or blood is usually related to the presence of malignant tumors and is regarded as a biomarker for the early diagnosis of cancer. Therefore, the detection of polyamine levels in physiological fluids can provide valuable information in terms of cancer diagnosis and in monitoring therapeutic effects. In this review, we summarize the recent advances in fluorescent methods for polyamine detection (supramolecular fluorescent sensing systems, fluorescent probes based on the chromophore reaction, fluorescent small molecules, and fluorescent nanoparticles). In addition, tumor polyamine-suppressing strategies (such as polyamine conjugate, polyamine analogs, combinations that target multiple components, spermine-responsive supramolecular chemotherapy, a combination of polyamine consumption and photodynamic therapy, etc.) are highlighted. We hope that this review promotes the development of more efficient polyamine detection methods and provides a comprehensive understanding of polyamine-based tumor suppressor strategies.

Keywords: detection; polyamines; suppressor strategies; tumor.

Figure 1

(a) Chemical structures of polyamines and their homologs. (b) A cartoon diagram of the polyamine fluorescence detection and polyamine suppression strategy in tumor treatment.

Figure 1

(a) Chemical structures of polyamines and their homologs. (b) A cartoon diagram of the polyamine fluorescence detection and polyamine suppression strategy in tumor treatment.

Scheme 1

A roadmap for the most common polyamine-monitoring methods.

Figure 2

Schematic illustration of the mechanism for sensing spermine, based on supraamphiphiles [44].

Figure 3

Proposed mechanism of the fluorescent probes for spermine and 1-adamantanamine, based on the supramolecular system formed between 2 and CB[7] [45].

Figure 4

Schematic representation of the three-component supramolecular sensing assembly for spermine, spermidine, and cadaverine [46].

Figure 5

Schematic representation of the three-component supramolecular sensing assay for spermine (and spermidine) [47].

Figure 6

Competitive/synergetic complexation among CB[7], γ-CD, spermine and pyrene [51].

Figure 7

The possible sensing mechanism between compound 6 and polyamines [62].

Figure 8

The possible sensing mechanism between compound 7 and polyamines [63].

Figure 9

The possible sensing mechanism between compound 8 and the polyamines [64].

Figure 10

Chemical structures of fluorescent probes 9 and 10 [65,66].

Figure 11

Chemical structures of polyamine analogs 11a–11f [73].

Figure 12

Chemical structures of the naphthalimide-polyamine conjugates, 12a–d, 13a–c and 14a–b [74].

Figure 13

Chemical structures of the flavonoid polyamine conjugates, 15a–15f [77].

Figure 14

Chemical structures of the naphthoquinone-polyamine conjugates, 16a–16c [81].

Figure 15

Supramolecular chemotherapy using oxaliplatin and CB[7] and its competitive release and replacement by spermine [86].

Figure 16

Supramolecular chemotherapy, based on host–guest complexation between carboxylated pillar[6]arene and oxaliplatin [91].

Figure 17

The combination of photodynamic therapy with a putative depletion of polyamines on cancer treatment with compound 17 [95].