Jul 2026· Organic and biomolecular chemistry· Vol 24, pp. 5859-5866· 0 citations
Medicine
TL;DR
This work rationally design and synthesize two novel carbazole-tricyanofuran (TCF)-based donor-π-acceptor (D-π-A) PSs (1 and 2), which exhibit broad absorption, NIR fluorescence, and efficient reactive oxygen species (ROS) generation under 590 nm light irradiation.
Abstract
Photodynamic therapy (PDT) integrated with near-infrared (NIR) fluorescence imaging emerges as a promising theranostic approach for precise cancer management, yet the development of biocompatible, targetable, and highly efficient photosensitizers (PSs) is still in urgent demand. Herein, we rationally design and synthesize two novel carbazole-tricyanofuran (TCF)-based donor-π-acceptor (D-π-A) PSs (1 and 2), which exhibit broad absorption, NIR fluorescence, and efficient reactive oxygen species (ROS) generation through both type-I and type-II pathways under 590 nm light irradiation. To improve water solubility, biocompatibility, and tumor-accumulation ability, triglycol (TEG)-functionalized glucose is conjugated onto the PS skeletons to construct glycosylated nano-PSs (1G and 2G). The glucose moieties enable active cellular uptake through overexpressed glucose transporters (GLUTs) on cancer cells. Both 1G and 2G retain favorable NIR optical properties and robust ROS generation capability in aqueous media. In vitro studies demonstrate that 1G and 2G possess negligible dark cytotoxicity and can realize specific NIR fluorescence bioimaging in A549 and HeLa cancer cells. Notably, 2G exhibits excellent photodynamic antitumor efficiency, effectively killing cancer cells upon light irradiation via ROS-mediated cell death. This work provides a feasible glycosylation strategy for constructing NIR-emissive organic nano-photosensitizers, offering a promising candidate for glucose-facilitated cancer theranostics.
Photodynamic therapy (PDT) offers a promising approach for cancer treatment, but developing photosensitizers (PSs) with tumor targeting and near-infrared (NIR) imaging capabilities remains challenging. Herein, we designed two donor–π–acceptor (D–π–A) type photosensitizers, TC1 and TC2, by bridging electron-rich carbazole with electron-withdrawing tricyanofuran (TCF) via thiophene or EDOT moieties. Both PSs exhibited broad absorption, NIR fluorescence emission (>650 nm), and efficient type-I/II reactive oxygen species (ROS) generation under light irradiation. To improve aqueous dispersibility and breast cancer targeting, we conjugated PEGylated mannose to TC1 and TC2, yielding glycol-nanoparticles TC1M and TC2M. These nanoparticles maintained desirable NIR optical properties and ROS generation capacity while exhibiting excellent biocompatibility. Notably, mannose receptor-mediated endocytosis enabled selective uptake by MDA-MB-231 breast cancer cells over normal bEnd.3 cells, allowing targeted fluorescence imaging. Furthermore, TC2M demonstrated potent photodynamic activity, reducing cell viability to 23.15% at 20 µM under light irradiation through efficient intracellular ROS generation. This study presents mannose-functionalized glycol-nanoparticles as promising targeted theranostic agents for NIR imaging and PDT of breast cancer.
Yu Tang, Zhu-Ting Song, Lu-Lu Sun et al.· RSC Advances· 0 citations
The clinical efficacy of photodynamic therapy (PDT) is fundamentally limited by the scarcity of efficient photosensitizers (PSs) and the oxygen dependence of singlet-oxygen-mediated cytotoxicity. Here we report pentaperylene decaimide selenide (PPD-Se), a nanographene-derived photoelectronic material that functions as a high-performance Type-II photosensitizer. PPD-Se exhibits broadband absorption (300-650 nm), enhanced intersystem crossing enabled by a selenium-induced heavy-atom effect, a small ΔEST (0.50 eV), and a high 1O2 quantum yield (ΦΔ = 0.40). To address hypoxia-limited PDT, PPD-Se nanoparticles were covalently integrated with microalgae to construct an algae@PPD-Se biohybrid, in which PPD-Se is shielded from premature activation yet undergoes glutathione (GSH)-triggered release in the tumor microenvironment. Cleavage of disulfide linkages restores the photosynthetic activity of algae, enabling light-driven O2 production that alleviates local hypoxia and simultaneously boosts PPD-Se-mediated ROS generation. The biohybrid exhibits enhanced intracellular uptake, amplified ROS production, and potent apoptosis induction under white light-emitting diode (LED) irradiation (400-700 nm, 1 mW·cm-2). In vivo, algae@PPD-Se significantly downregulates HIF-1α, restores intra-tumoral oxygenation, and achieves marked tumor growth inhibition without observable systemic toxicity. This study introduces a dual-functional optoelectronic-biological PDT platform that couples a newly designed nanographene photosensitizer with photosynthetic oxygenation, offering a mechanistically driven strategy to overcome the oxygen dependency of PDT.
Gongcheng Ma, Nan Zhang, Hongrong Shi et al.· Advanced Healthcare Material...· 0 citations
Conventional photosensitizers (PSs) are hindered by aggregation-caused quenching, limited tissue-penetration depth and off-target toxicity, which restricts their clinical translation for photodynamic therapy (PDT). To tackle these bottlenecks, we constructed an all-in-one nanotheranostic system named F127@546, where a donor-acceptor-type fluorophore (IR-546) with twisted intramolecular charge-transfer (TICT) characteristics is encapsulated within the amphiphilic polymer Pluronic F127. This rational design not only substantially improves biocompatibility but also induces a prominent emission red shift from 605 nm to 900 nm, with an emission tail extending above 1000 nm to realize high-resolution deep-tissue NIR-II imaging. Beyond its NIR-II imaging capability, F127@546 acts as an effective dual-mode photosensitizer upon 660 nm laser irradiation to concurrently produce type-I and type-II reactive oxygen species (ROS). The generated ROS dissipates mitochondrial membrane potential and further initiates melanoma cell apoptosis. In vivo experiments were performed via intratumoral injection of F127@546. We verified that its photodynamic therapy exerted a remarkable inhibitory effect on tumors, accompanied by negligible systemic toxicity. This study provides a generalizable blueprint for fabricating multifunctional nanoplatforms that combine deep tissue imaging and synergistic photodynamic therapy, advancing the development of precision-oriented anti-tumor treatment.
Li Liu, H. Liao, Jingyu Deng et al.· Journal of materials chemist...· 0 citations
The escalating global cancer burden, particularly in low- and middle-income countries, necessitates safer and more effective therapeutic strategies. The toxicity and environmental issues of traditional heavy-metal-based quantum dots (QDs) have been addressed by green-synthesised QDs, which have become a promising platform for nanomedicine. In photodynamic treatment (PDT), photothermal therapy (PTT), and theranostic applications, the anticancer effectiveness of green-synthesized QDs that are derived from plant extracts, microbes, biomolecules, and biomass waste is critically assessed. Green synthesis techniques, such as hydrothermal and microwave-assisted methods, provide biocompatible QDs with good photostability, tunable optical characteristics, and decreased cytotoxicity. Mechanistically, these QDs generate reactive oxygen species (ROS), induce mitochondrial dysfunction, produce localized hyperthermia upon near-infrared irradiation, and activate apoptotic pathways (such as p53, Bax/Bcl-2, and caspase cascade), leading to selective cancer cell death. Preclinical in vitro and in vivo studies demonstrate potent tumor ablation through passive (EPR effect) and active targeting strategies. Despite these advances, some key setbacks hinder their clinical translation: lack of standardized synthesis protocols, batch-to-batch variability, limited long-term biosafety data, suboptimal targeting efficiency, and regulatory hurdles. Future perspectives include AI-driven optimization, smart theranostic platforms integrating multimodal imaging and therapy, and sustainable circular economy approaches using biowaste. Addressing these challenges through harmonized protocols and rigorous preclinical validation will be essential to realize the full potential of green-synthesized QDs as safe, multifunctional, and effective cancer nanomedicines.
G. Kah, Heidi Abrahamse· RSC Advances· 0 citations
The development of novel antibacterial strategies for the treatment of pathogenic bacterial infections is urgent. Photodynamic therapy (PDT) is considered a promising solution. However, near-infrared (NIR) type I photosensitizers are still lacking for deep-tissue infection treatment. Herein, we construct a series of donor-acceptor (D-A) NIR-conjugated polymers with type I PDT through precise molecular engineering and systematically elucidate the structure-activity relationship between D-A architecture and type I reactive oxygen species (ROS) generation capacity. First, three D-A polymers are synthesized by pairing fluorene with different acceptors, among which TQT (6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline)-based conjugated polymer (VCP3) exhibits the highest ROS generation. Subsequent donor engineering with TQT as an acceptor affords NIR-absorbing polymers. In particular, NIR-conjugated polymer NCP3, bearing 2,7-di(thiophen-2-yl)fluorene as a donor, demonstrates outstanding type I ROS generation ability. The resulting cationic NCP3 NPs achieve efficient photodynamic antibacterial performance for treating bacterial abscesses in vivo with favorable biosafety. This work provides robust molecular engineering guidelines for designing NIR type I photosensitizers toward deep-tissue antibacterial therapy.
Ling Li, Junqing Wang, Kai-Yan Yang et al.· Journal of Physical Chemistr...· 0 citations
The hypoxic tumor microenvironment (TME) of hepatocellular carcinoma (HCC) featured overexpressed hypochlorite (ClO-), which represented both a biochemical hallmark and a potential therapeutic trigger. Herein, POR-CA, a near-infrared (NIR) activatable prodrug constructed by conjugating cinnamic acid to a 4-(4-aminophenyl) porphyrin fluorophore, was reported. Exposure to ClO- produced a concentration-dependent decrease in near-infrared fluorescence, enabling fluorescence-quenching sensing under the tested conditions. Spectroscopic characterization confirmed rapid and sensitive ClO- responsiveness with favorable pH stability. Notably, the porphyrin backbone acted as an intrinsic photosensitizer to generate reactive oxygen species (ROS) under 660 nm laser irradiation for photodynamic therapy (PDT). HRMS provided evidence consistent with ClO--induced cleavage and formation of a TAPP-related fragment. POR-CA exhibited differential dark cytotoxicity in HepG-2 and LO-2 cells and light-dependent phototoxicity under the tested conditions. These results supported POR-CA as an in vitro proof-of-concept platform integrating ClO--responsive fluorescence-quenching sensing with light-dependent phototoxicity, while the contribution of the released cinnamic-acid-derived component remained to be established. Nonetheless, this molecular design perspective served as a valuable reference for subsequent translational optimization.
Jinglin Gao, Lili Jia, Yibiao Liu et al.· Journal of Photochemistry an...· 0 citations