Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Abstract

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.

Keywords: cancer therapy; pseudomonas exotoxin; targeted toxin.

Figure 2

(a) Small unilamellar targeted liposomes containing PE40 [93]; (b) Hybrid biofunctional nanocomplex based on radioactive 90Y bearing core-shell UCNP and functionalized with targeted toxin DARPin-PE40 [97].

Figure 1

The main factors affecting the efficiency of targeted toxin. Green up arrows—factors enhancing circulation time and tumor cell targeting. Red down arrow—reducing factor. FcRn is the neonatal Fc receptor.

Figure 3

(a) Light propagation through the tissues; (b) Genetically encoded PSs. 3D model (ribbon representation) of miniSOG (PDB entry 6GPV) and KillerRed (PDB entry 2WIQ) was made using DS ViewerPro 5.0 software.

Figure 4

Bioluminescence system based on luciferase, furimazine, and miniSOG. (a) Normalized emission spectrum of furimamide (NanoLuc_em) and normalized absorption (miniSOG_abs) and emission (miniSOG_em) spectra of miniSOG. (b) Scheme of BRET-mediated system for deep PDT [165,166].

Figure 5

Nanoagents based on KillerRed and upconversion nanoparticls (UCNP). The deep-penetrating near infrared (NIR) light is converted to yellow light that is able to excite KillerRed [116].