Aggregation polymorphism of photoactivatable Pt(iv) prodrugs as a strategy for the design of theranostic nanomaterials Vladislav Bykusov, Ilia Kuzmichev, Maxim Stepanov, Dmitry Bunin, Yuriy Luponosov, Yulia Isaeva, Askold Trul, Roman Akasov, Tatiana Egorova, Alexander Erofeev, Regina Kuanaeva, Yulia Maksimova, Maxim Abakumov, Aleksey Nikitin, Vladimir Kuzmin, Anton Egorov, Ivan Burtsev, Igor A. Rodin, Mikhail F. Vokuev, Elena Beloglazkina, Olga Krasnovskaya Dalton Transactions, 2026 The design of multifunctional theranostic nanomaterials, including the application of J-aggregates as photothermal (PTT) and photodynamic (PDT) therapy agents, is in high demand.
Pt(IV)-BODIPY Nanoparticles for Photoinduced Tumor Ablation and NIR Light-Activated Chemotherapy Vladislav Bykusov, Ilia Kuzmichev, Yulia A. Isaeva, Maxim Stepanov, Roman A. Akasov, Lin Huang, Si Gao, Kun Qian, Petr V. Gorelkin, Alexander S. Erofeev, Regina Kuanaeva, Aleksey Nikitin, Vita N. Nikitina, Vugara Mamed-Nabizade, Yulia Maksimova, Igor A. Rodin, Mikhail F. Vokuev, Alexander G. Martynov, Dmitry Bunin, Maxim A. Abakumov, Nelly S. Chmelyuk, Polina Lazareva, Vadim S. Pokrovsky, Irina Khan, Elena K. Beloglazkina, Olga O. Krasnovskaya ACS Applied Nano Materials, 2026 Phototheranostics, which combine light-induced therapeutic and diagnostic modalities in a single platform, is a novel approach in tumor treatment and diagnostics. The development of dual-action nanomaterials with photothermal activity and the ability to act as photoactivated chemotherapy, capable of the light-induced release of chemotherapeutic agents, is a challenging task. However, different nanosystems reported to date represent either photoactivated chemotherapy (PACT), agents of photothermal therapy (PTT), or the loading of a drug and photoabsorber in a single polymer carrier. Herein, we report a near-infrared-light-activatable theranostic nanoplatform CF3-Pt-NPs with dual antitumor action, PTT/PACT, which is also capable of fluorescent and photothermal imaging of tumor tissues, based on the photoactivated Pt(IV) prodrug CF3-Pt with BODIPY in the axial position. A barrier-free CF3 rotor moiety in the BODIPY core provides excellent photothermal efficacy for the nanoplatform, while both the Pt(IV) prodrug CF3-Pt and nanoparticles CF3-Pt-NPs based on it act as PACT agents by releasing cisplatin under 740 nm light irradiation. Metabolomic profiles of CF3-Pt-NP-treated MCF-7 cells confirmed strong thermal- and cisplatin-induced responses of cells. CF3-Pt-NPs demonstrated the ability to accumulate in vivo in tumors, with the degree of fluorescence in the tumor correlating well with platinum accumulation, thereby confirming the ability of CF3-Pt-NPs to reach the tumor intact. A strong photothermal effect in vivo was confirmed after both intratumoral and intravenous administration of CF3-Pt-NPs with 808 nm laser irradiation. This is the first theranostic nanoplatform with dual PTT/PACT antitumor action, which is also capable of fluorescent and photothermal imaging of tumor tissues.
Near-infrared neural stimulation with conjugated polymer nanoparticles Yulia A. Isaeva, Elizaveta D. Blagodarnaia, Nikolay A. Aseyev, Olga S. Idzhilova, Maxim E. Stepanov, Liya A. Poletavkina, Anastasia A. Vetyugova, Pavel M. Balaban, Sergey A. Ponomarenko, Yuriy N. Luponosov Journal of Macromolecular Science Part A Pure and Applied Chemistry, 2026 Conjugated organic nanomaterials are a promising class of compounds for creating biointerfaces due to their unique optoelectronic properties, biocompatibility and capacity for chemical modification. Materials that absorb light in the near-infrared (NIR) region of the spectrum are in particularly high demand, as they enable light to penetrate deeper into biological tissues with minimal scattering. This study presents the synthesis of a new conjugated polymer, P-IDIC-TF, which has a donor-acceptor structure based on an indaceno[1,2-b:5,6-b’]dithiophene fragment and exhibits effective light absorption in the red and NIR spectral ranges. Using the nanoprecipitation method, without surfactants or encapsulating agents, aqueous dispersions of polymer nanoparticles (NPs) with an average hydrodynamic diameter of 55 nm were obtained. NPs demonstrate high stability and pose no toxicity to cells while exhibiting high photothermal conversion capacity. When applied to rat primary cortical neurons, the NPs depolarize cell membranes when irradiated with 730 nm light. These results highlight the potential of such polymeric nanosystems as non-invasive, light-controlled nanoactuators, as well as artificial photosensitive pigments, for use in bioelectronics and biomedicine.
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, Ivan V. Dyadishchev, Askold A. Trul, Tatyana V. Egorova, Roman A. Akasov, Yuriy N. Luponosov 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.
Photoactivatable Cisplatin-Combretastatin-BODIPY Pt(IV) Prodrug for Dual-Action Light-Controlled Chemotherapy Daniil V. Spector, Georgy Karetnikov, Anna Bubley, Roman A. Akasov, Yulia A. Isaeva, Tatiana V. Egorova, Alexander G. Martynov, Dmitry Bunin, Dmitry A. Skvortsov, Daria Ipatova, Alexander S. Erofeev, Petr V. Gorelkin, Vugara Mamed-Nabizade, Vasilii S. Kolmogorov, Alexander N. Vaneev, Igor A. Rodin, Mikhail F. Vokuev, Yuri K. Grishin, Vitaly A. Roznyatovsky, Vita N. Nikitina, Elena K. Beloglazkina, Olga O. Krasnovskaya ACS Pharmacology and Translational Science, 2025 Herein, we designed, synthesized, and studied the activity of a novel dual-action red light-activatable Pt(IV) prodrug BDP-Pt-CA4 with a BODIPY fluorophore and CA4 in axial positions, capable of light-controlled release of two chemotherapeutic drugs: cisplatin and combretastatin A4 (CA4). To the best of our knowledge, this is the first example of a dual-action photoactive Pt(IV)-CA4 prodrug that releases two antiproliferative agents upon red light irradiation. The aim of this work was to demonstrate light-induced release of CA4 and cisplatin from the prodrug, occurring strictly on demand to reduce the overall toxicity of the drug and minimize the damaging effect on normal tissues. In addition to in vitro evidence of light-induced release of two chemotherapeutic agents, a controllable release of both drugs inside cancer cells was also proven. For the first time, a light-induced release of the tubulin polymerization inhibitor from a photoactivatable prodrug was observed via quantification of subtle changes in the mechanistic properties of cell surfaces via single-cell low-stress scanning ion conductance microscopy (SICM). Our results clearly demonstrate a perspective for photoactive Pt(IV) prodrugs, confirming an ability to release the platinum agent “on demand”, and to act as light-controlled dual-action chemotherapy.
Green Light Activated Dual-Action Pt(IV) Prodrug with Enhanced PDT Activity Daniil Spector, Vladislav Bykusov, Yulia Isaeva, Roman Akasov, Anastasia Zharova, Igor Rodin, Mikhail Vokuev, Yuri Grishin, Vita Nikitina, Alexander Martynov, Vladimir Kuzmin, Elena Beloglazkina, Olga Krasnovskaya 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, Vitaly A Roznyatovsky, Yuri Konstantinovich Grishin, Elena Kimovna Beloglazkina, Olga Olegovna Krasnovskaya 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.
Nanoformulation of the Photoactive Cisplatin Prodrug for Combined Photothermal Therapy and Bioimaging Daniil V. Spector, Vladislav Bykusov, Anastasia Zharova, Ilia Kuzmichev, Yulia A. Isaeva, Evgeny V. Khaydukov, Ekaterina Trifanova, Maxim Stepanov, Alexander S. Erofeev, Petr Gorelkin, Regina Kuanaeva, Vita N. Nikitina, Alexander Dubenskii, Yulia Maksimova, Dmitry Aleksandrovich Skvortsov, Daria Ipatova, Igor A. Rodin, Mikhail F. Vokuev, Alexander G. Martynov, Dmitry Bunin, Vadim S. Pokrovsky, Gulalek Babayeva, Tamara Uskova, Maxim A. Abakumov, Elena K. Beloglazkina, Roman A. Akasov, Olga O. Krasnovskaya ACS Applied Nano Materials, 2024 Cancer phototheranostics is a new mode of precise treatment based on fluorescent and photothermal imaging (PTI), combined with photodynamic (PDT) and photothermal therapy (PTT). Herein, we designed a photoactive Pt(IV) prodrug Pt-1 with BODIPY-based triplet photosensitizer as an axial ligand that exhibits cytotoxic effects through both PDT and photoactivated chemotherapy (PACT). Based on the Pt-1 prodrug, we developed a multifunctional theranostic nanoplatform Pt-NPs with combined PDT/PTT activity, capable of light-induced cisplatin release and suitable for photothermal and fluorescent tumor imaging. Upon 660 nm laser irradiation, Pt-NPs efficiently causes regional hyperpyrexia, with a photothermal conversion efficiency of 42.1%. Synergistically, Pt-NPs acts as a PDT type I agent. In vivo PTI studies have shown bright fluorescence of the CT-26 tumor after intravenous injection of Pt-NPs, indicating accumulation and retention of Pt-NPs in the tumor. This is the first example of PTT/PDT-active NPs based on Pt(IV) prodrug capable of photoinduced release of cisplatin. This strategy of the synergistic light-induced PDT/PTT/PACT action of Pt-NPs provides a new platform for the future design of phototheranostic agents for enhanced tumor treatment and imaging.
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, Elena A. Kotova, Tikhon S. Kurkin, Liya A. Poletavkina, Yulia A. Isaeva, Yuri N. Antonenko, Pavel M. Balaban, Sergey A. Ponomarenko 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.
