The combination of the Ce6/PP123 NCs with a novel wearable OLED is a promising platform for effective and safe PDT in cancer treatment and shows optimal spectral characteristics and the highest therapeutic efficacy in vitro.
Abstract
Photodynamic therapy (PDT) is a minimally invasive cancer treatment strategy. Despite numerous studies confirming its potential advantages, the clinical translation of this technique remains limited owing to the impracticality of using conventional light sources and the instability of photosensitizers. This study presents a novel PDT approach that utilizes organic light‐emitting diodes (OLEDs) as compact, low‐thermal, wearable, and flexible light sources to activate chlorin e6 (Ce6)‐loaded Pluronic nanocapsules (Ce6/Plu NCs) for anticancer therapy. Here, different types of Pluronic polymers are used and optimized to synthesize ∼120 nm‐diameter Ce6/Plu NCs. Among the formulated systems, the Ce6/PP123 NCs show optimal spectral characteristics and the highest therapeutic efficacy in vitro, and efficient tumor accumulation after intravenous injection and significant antitumor efficacy upon OLED irradiation with minimal off‐target toxicity in vivo. Tissue‐attachable OLEDs for PDT can be placed in close proximity to tumor tissue for efficient light delivery. The combination of the Ce6/PP123 NCs with a novel wearable OLED is a promising platform for effective and safe PDT in cancer treatment.
This review highlights mechanisms, recent advances, and translational challenges of natural PS‐based nanotherapeutics across multiple cancers, emphasizing strategies to improve delivery, selectivity, and therapeutic outcomes for next‐generation PDT.
Nanomedicine has reshaped healthcare, especially in targeted drug delivery systems (DDSs) and diagnostics, addressing the limitations of traditional cancer therapies. Integration of photodynamic therapy (PDT) with nanoparticle‐based DDSs has significantly improved the targeted accumulation and pharmacokinetic properties of photosensitizers within tumor cells, enabling selective tumor cell death while sparing healthy tissues. This study developed chitosan‐sericin polyelectrolyte nanoparticles (CSSN NPs) via the Flash nanocomplexation (FNC) technique to enhance the 5‐aminolevulinic acid (5‐ALA) delivery, a precursor of protoporphyrin IX (PpIX), and evaluated their potential in PDT against the MCF‐7 breast cancer cell line. The 5‐ALA‐loaded CSSN NPs exhibited a hydrodynamic diameter ≤100 nm, a positive surface charge, and an encapsulation efficiency of ∼92% with a controlled release profile in acidic environments. In vitro assays demonstrated a ∼40% reduction in cell viability compared with free 5‐ALA, further confirmed by elevated red fluorescence observed in the Calcein/Propidium iodide assay. Confocal microscopy revealed strong PpIX red fluorescence and increased perinuclear accumulation, indicating effective cellular uptake. PpIX phototoxicity was validated by reactive oxygen species induction upon irradiation. These innovative biopolymer‐based DDSs demonstrate considerable potential in enhancing the therapeutic efficacy of 5‐ALA and improving PDT outcomes, setting the stage for future advancements in targeted cancer therapies.
Athira Narayanan, Benedetta di Chiara Stanca, Daniela Pinheiro et al.· Visual Information Expert Wo...· 0 citations
Cancer phototherapies, such as photodynamic therapy (PDT) and photothermal therapy (PTT), are often limited by poor tumor accumulation, insufficient penetration, and lack of real-time adaptability to the tumor microenvironment. To address these challenges, we developed an intelligent nanoscale theranostic nanoplatform, TDNHM-Au@IR780, based on a DNA tetrahedron (TDN) functionalized with gold nanoparticles (AuNPs) and the near-infrared dye IR780. The platform is further equipped with MUC1-targeting aptamers and catalytic hairpin assembly (CHA) circuits responsive to the tumor biomarker miRNA-21. Upon encountering miRNA-21 in the tumor microenvironment, the nanoparticles undergo in situ aggregation via CHA, dynamically switching from small, penetrative particles to larger aggregates that enhance retention. Under 808 nm laser irradiation, the aggregated system exhibits strong plasmonic coupling, achieving a high photothermal conversion efficiency of 45.8% and significantly amplified singlet oxygen generation. In vitro and in vivo studies using 4T1 breast cancer models demonstrate effective tumor-targeted accumulation, excellent biocompatibility, and potent synergistic photothermal/photodynamic effects. This nanoscale, dynamically responsive strategy is particularly well-suited for image-guided precision phototherapy of breast cancer, offering a promising avenue for nanomedicine-based oncology.
Zhuoran Lin, Wenjing Wu, Hang Zhao et al.· ACS Applied Nano Materials· 0 citations
Urothelial carcinoma is a common urinary malignancy with high recurrence, easy progression to muscle-invasive disease, and resistance to conventional therapies. To address the clinical challenges of poor drug retention, low bioavailability, severe toxicity, and the inability of monotherapy to inhibit tumor recurrence and metastasis, a smart responsive nanoplatform (PMP@ED/Ba) based on mesoporous polydopamine (MPDA) was designed and constructed. This platform uses a thermosensitive phase-change material as a gatekeeper to co-load erdafitinib (FGFR inhibitor) and baicalein (antioxidant). Systematic characterizations confirmed the successful fabrication of the nanocomposite with uniform spherical morphology. Under 808 nm NIR irradiation, PMP@ED/Ba exhibited good concentration- and power-dependent heating and photothermal stability, with a photothermal conversion efficiency of 26.3%. The PCM gatekeeper enabled NIR triggered on-demand drug release, preventing premature leakage. DPPH/ABTS assays demonstrated potent non-enzymatic antioxidant activity, efficiently depleting ROS. Hemocompatibility and cytotoxicity tests confirmed good biocompatibility. In vitro and in vivo studies showed that PMP@ED/Ba plus NIR irradiation significantly suppressed T24 tumor growth through synergistic photothermal-chemotherapy, inducing extensive apoptosis and necrosis without major organ toxicity. This smart platform provides an efficient, low-toxicity strategy for locoregional treatment of urothelial carcinoma.
Fayou Zhou, Jun Wang, Rui Xu et al.· Colloids and Surfaces B: Bio...· 0 citations
Photodynamic therapy (PDT) faces significant challenges in treating solid tumors due to the hypoxic tumor microenvironment and high degree of tumor heterogeneity. To address this issue, this study employed a strategy of acceptor planarization coupled with tunable terminal aryl modulation to design and synthesize a series of type I photosensitizers (DPP‐1–DPP‐3) with systematically tuned push–pull character and electronic structures. Among them, DPP‐3 exhibits outstanding near‐infrared emission and hypoxia‐tolerant reactive oxygen species generation. Building on this core module, we integrated a biomarker‐responsive unit into DPP‐3 to construct an intelligent theranostic probe, DPP‐CE. This probe retains high photodynamic activity both before and after activation, ensuring reliable therapeutic efficacy independent of local activation efficiency, while its near‐infrared fluorescence signal is specifically activated only within the tumor microenvironment, enabling imaging‐guided precise treatment. Both in vitro and in vivo experiments demonstrate that DPP‐CE allows high‐contrast fluorescence imaging of tumors and effectively inhibits tumor growth under both normoxic and hypoxic conditions, while showing good biosafety. This work not only provides a new strategy for developing high‐performance type I photosensitizers, but also offers a modular approach that integrates a therapeutic core with a biomarker‐responsive unit, paving the way toward programmable theranostic platforms adaptable to tumor heterogeneity.
Xuemei Dong, Lingan Zeng, Yunlong Liu et al.· Advanced Healthcare Material...· 1 citation
In this study, we investigated the tumor-accumulating efficacy of photodynamic therapy (PDT) mediated by an aluminum chloride phthalocyanine-loaded nanoemulsion (AlClPc-NE) against breast cancer (MCF-7 and MDA-MB-231) and non-tumorigenic (MCF-10A) cell lines. The optimized AlClPc-NE formulation exhibited a mean hydrodynamic diameter of 168 nm, zeta potential of − 29 mV, low polydispersity (0.25), encapsulation efficiency of 81.10%, and estimated stability of 12 months. The system effectively preserved the drug photoactivity, achieving a robust singlet oxygen quantum yield (ΦΔ = 0.52). In vitro assays confirmed excellent dark biocompatibility of the nanocomposites. Upon irradiation, AlClPc-PDT exhibited potent phototoxicity. Crucially, a selective therapeutic window was observed 24 h post-treatment at a light density of 1000 mJ/cm2, significantly reducing tumor cell viability by over 50% while preserving non-tumorigenic MCF-10A cells. This enhanced efficacy is attributed to the optimized cellular internalization and specific subcellular localization promoted by nanoemulsions. Translating these findings to an in vivo orthotopic breast cancer model, AlClPc-PDT significantly suppressed tumor progression, reducing the tumor mass by approximately 50%. Ultimately, the AlClPc-NE platform emerged as a highly localized therapeutic strategy, prioritizing tumor eradication while limiting the potential side effects in healthy tissues. A stable AlClPc-loaded nanoemulsion with high encapsulation efficiency and preserved photoactivity was successfully developed for photodynamic therapy applications. AlClPc-NE promoted enhanced cellular internalization and selective phototoxicity against breast cancer cells while preserving non-tumorigenic cells 24 h post-treatment. The nanoemulsion maintained the photosensitizer in an active monomeric state, achieving a high singlet oxygen quantum yield (ΦΔ = 0.52). In vivo photodynamic therapy mediated by AlClPc-NE significantly suppressed orthotopic breast tumor progression, reducing the tumor burden by approximately 50% under these conditions. A stable AlClPc-loaded nanoemulsion with high encapsulation efficiency and preserved photoactivity was successfully developed for photodynamic therapy applications. AlClPc-NE promoted enhanced cellular internalization and selective phototoxicity against breast cancer cells while preserving non-tumorigenic cells 24 h post-treatment. The nanoemulsion maintained the photosensitizer in an active monomeric state, achieving a high singlet oxygen quantum yield (ΦΔ = 0.52). In vivo photodynamic therapy mediated by AlClPc-NE significantly suppressed orthotopic breast tumor progression, reducing the tumor burden by approximately 50% under these conditions.
C. C. Jayme, D. S. Fernandes, F. S. Matsuo et al.· Discover Nano· 0 citations
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