A Tumor-Targeting Near-Infrared Heptamethine Cyanine Photosensitizer with Twisted Molecular Structure for Enhanced Imaging-Guided Cancer Phototherapy

Abstract

In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.

Anionic Cyanine J‐Type Aggregate Nanoparticles with Enhanced Photosensitization for Mitochondria‐Targeting Tumor Phototherapy

“…Notably, the temperature increase of C3T-X NPs only has a little reduction during four heating and cooling cycles (100 min) (Figure S19), strongly indicating the better photostability of C3T-X NPs than that reported from ICG. [30] This conclusion was further confirmed by the photostability tests of ICG and C3T-Pc NPs under white light irradiation (0.3 W cm À 2 ), as shown in Figure S20.…”

Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor‐Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity

“…Next, we calculated the photothermal conversion efficiency (PCE) of ER‐Cy‐ po NO 2 based on a heating‐cooling cycle experiment. [ 18,33 ] The PCE of ER‐Cy‐ po NO 2 was 47.5% (Figure S21, Supporting Information), which was much higher than most previously reported heptamethine cyanines (PCE, 3–40%). [ 18 ] For the photodynamic study, we determined the 1 O 2 generation using a singlet oxygen sensor green (SOSG) probe as an indicator.…”

“…[ 18,33 ] The PCE of ER‐Cy‐ po NO 2 was 47.5% (Figure S21, Supporting Information), which was much higher than most previously reported heptamethine cyanines (PCE, 3–40%). [ 18 ] For the photodynamic study, we determined the 1 O 2 generation using a singlet oxygen sensor green (SOSG) probe as an indicator. ER‐Cy‐ po NO 2 had the strongest fluorescence intensity with SOSG.…”

“…According to previous reports, [ 18,29 ] heptamethine cyanine dyes containing two N ‐alkyl side chains with three carbons in length, was shown to have excellent accumulation in tumors. Thus, we introduced two benzenesulfonamide groups (ER‐targeting moiety) into two N ‐alkyl side chains (three carbons) of heptamethine cyanine dyes to achieve ER‐specific accumulation in tumors ( Figure a).…”

“…In recent years, a class of multifunctional heptamethine cyanines have been developed by our group [14][15][16][17] as well as others. [18][19] These cyanine dyes exhibit tumor-targeting, near-infrared (NIR) imaging, or/and simultaneous phototherapy properties without relying on large polymers or heavy metal-based nanomaterials. They can preferentially accumulate in a variety of cancer cells and tumor xenografts through organic-anion-transporting polypeptide transporters (OATPs), which are often overexpressed on the surface of cancer cells.…”