Near-Infrared Activated Cyanine Dyes As Agents for Photothermal Therapy and Diagnosis of Tumors

Abstract

Today, it has become apparent that innovative treatment methods, including those involving simultaneous diagnosis and therapy, are particularly in demand in modern cancer medicine. The development of nanomedicine offers new ways of increasing the therapeutic index and minimizing side effects. The development of photoactivatable dyes that are effectively absorbed in the first transparency window of biological tissues (700-900 nm) and are capable of fluorescence and heat generation has led to the emergence of phototheranostics, an approach that combines the bioimaging of deep tumors and metastases and their photothermal treatment. The creation of near-infrared (NIR) light-activated agents for sensitive fluorescence bioimaging and phototherapy is a priority in phototheranostics, because the excitation of drugs and/or diagnostic substances in the near-infrared region exhibits advantages such as deep penetration into tissues and a weak baseline level of autofluorescence. In this review, we focus on NIR-excited dyes and discuss prospects for their application in photothermal therapy and the diagnosis of cancer. Particular attention is focused on the consideration of new multifunctional nanoplatforms for phototheranostics which allow one to achieve a synergistic effect in combinatorial photothermal, photodynamic, and/or chemotherapy, with simultaneous fluorescence, acoustic, and/or magnetic resonance imaging.

Keywords: cyanines; near infrared; photothermal therapy.

Fig. 1

Depth of light penetration of human tissues

Fig. 2

Visible and infrared absorption spectra of biological tissues (adapted from [9])

Fig. 3

General structure of cyanine dyes (A); structure of indocyanine green (ICG) (B); excitation and emission spectra of ICG (C)

Fig. 4

Nanosystems for the delivery of ICG to tumor cells. A – folic acid-functionalized multilayer lipid nanoparticles loaded with ICG [76]; B – chitosan nanospheres with encapsulated gold nanorods and ICG [77]; C – wolfram oxide nanorods with surface-bound ICG [78]; D – polyallylamine hydrochloride–phosphoric acid salt nanospheres loaded with ICG and functionalized with anti-human epidermal growth factor receptor (EGFR) antibodies [57]; E – self-organized nanoparticles consisting of human serum albumin (HSA), paclitaxel (PTX), and ICG [79]

Fig. 5

Structures of cyanine dyes (ICG analogs)

Fig. 6

Multifunctional platforms based on ICG dye analogs for phototheranostics. A – upconverting nanoparticles with bovine serum albumin (BSA) incorporating Rose Bengal and IR825 [109]; B – heparin and folic acid-based nanoparticles loaded with IR780 [58]; C – conjugates of human serum albumin (HSA) and CySCOOH [91]; D – gadolinium nanoparticles coated with a BSA-Cypate conjugate [113]