From Small Molecules to Polymers: Developing Non-Fullerene Acceptors for Efficient NIR Photothermal Cancer Therapy Yulia A. Isaeva, Elizaveta D. Blagodarnaia, Anastasia A. Vetyugova, Maxim E. Stepanov, Liya A. Poletavkina, et al. Polymers, 2025 Developing organic photothermal agents that are highly stable and have tunable electronic properties is important for advancing low-invasive cancer therapy. In this study, we present the synthesis and evaluation of three conjugated photothermal agents inspired by non-fullerene Y-series acceptors: the small molecule BTPT-OD, as well as two of its polymer derivatives with regular (r-BTPT) and irregular (ir-BTPT) structures. All of the compounds absorb light effectively in the red and near-infrared spectral ranges, with absorption maxima from 734 to 746 nm, and form stable nanoparticles (NPs) via nanoprecipitation, ranging in size from 13 to 39 nm. NPs exhibited negative surface charges, with ζ-potentials of −12.9, −15.5, and −17.9 mV for BTPT-OD, r-BTPT, and ir-BTPT NPs, respectively. Irradiation at a wavelength of 730 nm revealed that r-BTPT and ir-BTPT polymer NPs exhibited a 22- to 40-fold greater phototoxicity against A-549, Sk-Br-3, and MCF-7 human carcinoma cells than the non-polymeric analogue BTPT-OD. The measured photothermal conversion efficiencies ranged from 24 to 27 ± 5%. At the same time, the intracellular ROS generation quantified by the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) assay was low, allowing us to propose heat-mediated photothermal therapy as a more significant cell death predictor than ROS-mediated photodynamic therapy. This work is one of the first to compare small and polymeric non-fullerene acceptor materials for phototherapy purposes, demonstrating the advantages of using polymers.
Green Light Activated Dual-Action Pt(IV) Prodrug with Enhanced PDT Activity Daniil Spector, Vladislav Bykusov, Yulia Isaeva, Roman Akasov, Anastasia Zharova, et al. Chemmedchem, 2025 Light induced release of cisplatin from Pt(IV) prodrugs is a promising tool for precise spatiotemporal control over the antiproliferative activity of Pt‐based chemotherapeutic drugs. A combination of light‐controlled chemotherapy (PACT) and photodynamic therapy (PDT) in one molecule has the potential to overcome crucial drawbacks of both Pt‐based chemotherapy and PDT via a synergetic effect. Herein we report green‐light‐activated Pt(IV) prodrug GreenPt with BODIPY‐based photosentitizer in the axial position with an incredible high light response and singlet oxygen generation ability. GreenPt demonstrated the ability to release cisplatin under low‐dose green light irradiation up to 1 J/cm2. The investigation of the photoreduction mechanism of GreenPt prodrug using DFT modeling and ΔG0 PET estimation revealed that the anion‐radical formation and substituent photoinduced electron transfer from the triplet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light‐induced release of cisplatin. Green‐light‐activated BODIPY‐based photosentitizers 5 and 8 demonstrated outstanding photosensitizing properties with an extraordinary phototoxicity index (PI)>1300. GreenPt prodrug demonstrated gradual intracellular accumulation and light‐induced phototoxicity with PI>100, thus demonstrating dual action through light‐controlled release of both cisplatin and a potent BODIPY‐based photosensitizer.
Platinum(iv) prodrugs with heavy-atom-free BODIPY in axial position: instant photoactivation, enhanced biosafety and improved phototoxicity Daniil Victorovich Spector, Anastasia Olegovna Zharova, Yulia A Isaeva, Mikhail F Vokuev, Igor A Rodin, et al. Mendeleev Communications, 2025 Two new photoactivable Pt<sup>IV</sup> prodrugs bearing heavy-atomfree BODIPY in the axial position and differing in the linker length were prepared using CuAAC cycloaddition. Under 530 nm green light, both prodrugs produce singlet oxygen and are capable of a rapid cisplatin release in the presence of sodium ascorbate. Investigation of antiproliferative activity demonstrated excellent biosafety of these prodrugs, as well as outstanding phototoxicity under 530 nm low-dose green light.
Nanoparticles of Push-Pull Triphenylamine-Based Molecules for Light-Controlled Stimulation of Neuronal Activity Yuriy N. Luponosov, Alexander N. Solodukhin, Nikolay A. Aseyev, Tatyana I. Rokitskaya, Darya E. Kolotova, et al. ACS Biomaterials Science and Engineering, 2024 Organic semiconductor materials with a unique set of properties are very attractive for interfacing biological objects and can be used for noninvasive therapy or detection of biological signals. Here, we describe the synthesis and investigation of a novel series of organic push-pull conjugated molecules with the star-shaped architecture, consisting of triphenylamine as a branching electron donor core linked through the thiophene π-spacer to electron-withdrawing alkyl-dicyanovinyl groups. The molecules could form stable aqueous dispersions of nanoparticles (NPs) without the addition of any surfactants or amphiphilic polymer matrixes with the average size distribution varying from 40 to 120 nm and absorption spectra very similar to those of human eye retina pigments such as rods and green cones. Variation of the terminal alkyl chain length of the molecules forming NPs from 1 to 12 carbon atoms was found to be an efficient tool to modulate their lipophilic and biological properties. Possibilities of using the NPs as light nanoactuators in biological systems or as artificial pigments for therapy of degenerative retinal diseases were studied both on the model planar bilayer lipid membranes and on the rat cortical neurons. In the planar bilayer system, the photodynamic activity of these NPs led to photoinactivation of ion channels formed by pentadecapeptide gramicidin A. Treatment of rat cortical neurons with the NPs caused depolarization of cell membranes upon light irradiation, which could also be due to the photodynamic activity of the NPs. The results of the work gave more insight into the mechanisms of light-controlled stimulation of neuronal activity and for the first time showed that fine-tuning of the lipophilic affinity of NPs based on organic conjugated molecules is of high importance for creating a bioelectronic interface for biomedical applications.
