Aug 2026· Pharmaceutics· Vol 18, pp. 989· 0 citations· 95 references
Medicine
TL;DR
Liposome-encapsulated BODIPYs represent promising PDT agents by improving cellular uptake and eliciting robust antitumor activity through complementary cell death mechanisms, supporting the development of third-generation, tumor-targeted photosensitizers and warranting further preclinical investigation.
Abstract
Background: Photodynamic therapy (PDT) is a cancer treatment that combines a photosensitizer (PS), light, and oxygen to generate reactive oxygen species (ROS), leading to tumor cell death. PDT efficacy depends largely on PS accumulation within tumors, prompting the development of third-generation PSs and nanotechnology-based delivery systems. Among these, BODIPYs (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) are promising PSs due to their favorable photophysical properties, while liposomes improve drug delivery, cellular uptake, and sustained release profiles. This study describes the synthesis of two novel BODIPY derivatives differing in the position of a methyl ester group on the meso-phenyl ring, their incorporation into liposomes, and evaluation of PDT efficacy. Methods: Cellular uptake of BODIPY-loaded liposomes, intracellular ROS generation, apoptosis, necrosis, and lipid peroxidation were assessed by flow cytometry in colorectal and ovarian cancer cell lines. The antitumor activity of the liposomal formulations was further evaluated in both 2D and 3D models using MTT and clonogenic assays. The involvement of ferroptosis and necroptosis in PDT-induced cell death was also investigated. Results: Liposomal formulations significantly enhanced cellular uptake compared with free compounds. Following light activation, both formulations induced potent antitumor effects through multiple cell death mechanisms, including canonical and non-canonical pathways, and maintained strong efficacy in 3D tumor spheroids. Conclusions: Liposome-encapsulated BODIPYs represent promising PDT agents by improving cellular uptake and eliciting robust antitumor activity through complementary cell death mechanisms. Furthermore, the methyl ester substituent on the meso-phenyl ring provides a versatile platform for future conjugation with targeting ligands, supporting the development of third-generation, tumor-targeted photosensitizers and warranting further preclinical investigation.
Introduction Objective: Combination therapy is considered an effective strategy to improve cancer treatment outcomes. This study aimed to develop a Pluronic F127-based nano-codelivery system (FDC) encapsulating docetaxel (DTX) and chlorin e6 (Ce6) to enhance the efficacy of PDT using Ce6 and the chemotherapy effect of docetaxel (DTX).
METHODS
FDC was prepared by the thin film hydration method. Particle size, polydispersity index (PDI), zeta potential, drug loading efficiency, and 7‑day colloidal stability were characterized. Cellular uptake, reactive oxygen species (ROS) generation (using DCFH‑DA and SOSG probes), cytotoxicity (MTT assay), apoptosis (flow cytometry), and live/dead staining were evaluated in 4T1 breast cancer cells under light irradiation (630 nm, 29.8 mW/cm², 5 min). Statistical comparisons used Student's t‑test or one‑way ANOVA, with p < 0.05 considered significant.
RESULTS
FDC exhibited a uniform hydrodynamic diameter of 200.33 ± 7.71 nm, a PDI of 0.392 ± 0.03, high drug loading efficiency, and good stability over 7 days. Compared with free Ce6, FDC significantly enhanced cellular uptake of Ce6 and markedly increased ROS generation upon light irradiation (p < 0.01). Cytotoxicity assays, apoptosis analysis, and live/dead staining also showed that FDC plus light induced the strongest anti-tumor effect, showing better antitumor effect than free Ce6, free DTX, and the physical mixture of Ce6+DTX Discussion: The improved anti-tumor effect of FDC may be related to enhanced cellular uptake of Ce6 and the co-delivery of DTX and Ce6.
CONCLUSION
The FDC nano-co-delivery system represents a promising strategy for chemotherapy combined with photodynamic therapy against breast cancer.
Hua Cai, Yi Cen, Nannan Zhao et al.· Current Drug Delivery· 0 citations
A biochemical engineering approach for the development of photosensitizer-containing tumor cell targeted liposomes (TTLs) that may be used to enhance the efficacy of PDT are presented.
Mans Broekgaarden, R. V. Vught, S. Oliveira et al.· 0 citations
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.
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
This protocol presents methods for fabricating and characterising two distinct verteporfin (VP)-integrated lipid nanoparticle formulations and demonstrates knockout of up to approximately 326 slow-muscle fibres per zebrafish embryo via light activation and significant tumour growth suppression via X-ray-triggered doxorubicin release.
Yagiz A. Aksoy, Biyao Yang, G. Liew et al.· Journal of Visualized Experi...· 0 citations
A novel lipid droplet-targeted aggregation-induced emission photosensitizer CTC was designed and synthesized, providing a novel candidate and new insight for safe and efficient breast cancer PDT.
Yukun Zhang, Lidong Deng, Qiyan Li et al.· Bioorganic chemistry (Print)· 0 citations
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