Search Results (27)

Breast cancer remains a leading cause of cancer-related mortality worldwide, with treatment resistance, recurrence, and metastasis significantly limiting the effectiveness of conventional therapies. Photodynamic therapy (PDT) has emerged as a minimally invasive and highly selective approach, utilizing photosensitizer-generated reactive oxygen species (ROS) to achieve precise tumor cytotoxicity while preserving surrounding healthy tissue. However, clinical translation of PDT remains constrained by critical biological barriers within the tumor microenvironment, including tumor hypoxia, limited light penetration, poor photosensitizer stability, and inefficient cellular uptake. Antigen-targeted liposomal nanocarriers offer a compelling solution by enabling targeted drug delivery and tumor-specific photosensitizer accumulation, prolonged systemic circulation, and enhanced cellular internalization. Their multifunctional architecture uniquely supports combinational therapeutic strategies, integrating PDT with chemotherapy, photothermal therapy, gene therapy, X-ray-induced photodynamic therapy (X-PDT) and immune checkpoint blockade, thereby amplifying antitumor efficacy and overcoming drug resistance mechanisms. This review comprehensively summarizes recent advances in liposome-based PDT for breast cancer, highlighting multimodal therapeutic integration. Special emphasis is placed on preclinical and emerging clinical outcomes, pilot-scale manufacturing considerations, and strategies to minimize immune clearance. Full article

Background: The combination of photodynamic therapy (PDT) and immunotherapy has been explored as an innovative approach to enhance efficacy against tumors. However, PDT shows limited effectiveness in treating deep-seated tumors, as light and lasers do not sufficiently penetrate tissue. Methods: Herein, we introduced a nanocarrier (NP_VR) via self-assembly, using an amphiphilic copolymer to co-deliver the hydrophobic photosensitizer verteporfin (VP) and the immunoadjuvant imiquimod (R837). Results: Our X-ray-induced photodynamic therapy (X-PDT) mechanism induced NP_VR to generate a large amount of cytotoxic reactive oxygen species (ROS), which directly killed cancer cells. Moreover, the released R837 facilitated immunogenic cell death following the X-PDT process and promoted the maturation of dendritic cells (DCs), thereby eliciting immune responses against malignant triple-negative breast cancer (TNBC). In animal experiments, the combined therapy using NP_VR showed a tumor growth inhibition rate of ~70%. Conclusions: This novel strategy opens new avenues to designing next-generation nanomedicines for use in immunotherapy and other combination therapies. Full article

Context: X-ray-induced photodynamic therapy (X-PDT) is an emerging modality for deep-tumor treatment, leveraging radiosensitizing nanoprobes to enhance therapeutic effects. Problem: However, the efficacy of X-PDT is critically dependent on the incident X-ray energy, and the selection of an optimal spectrum remains a significant clinical challenge. Motivation: A systematic approach to optimizing X-ray energy is crucial for maximizing dose enhancement and translating X-PDT’s potential into effective clinical outcomes. Aim: This study therefore aims to identify the optimal X-ray energy for X-PDT by systematically evaluating the dose enhancement provided by nanoprobes across a range of clinically relevant energies. Proposed Methodology: We developed a Geant4-based Monte Carlo model to simulate the absorbed dose in a tumor phantom, both with and without X-PDT nanoprobes, under various X-ray energies (20–160 kVp). The dose enhancement ratio (DER) was calculated to quantify the sensitization effect. To validate our model, the simulated dose data were directly correlated with in vivo experimental tumor growth inhibition (TGI) rates. Main Results: The absorbed dose peaks at shallow depths (<1.0 mm), and the 60 kVp X-ray beam yielded the highest peak dose and the maximum DER. Furthermore, the absorbed dose calculated in the model incorporating nanoprobes showed a stronger correlation with experimental TGI than the model without them, confirming the simulation’s predictive value. Conclusions: There is an optimized X-ray excitation energy value for maximizing the therapeutic effect for X-PDT. The simulation method provides a potential way to optimize the treatment protocols for X-PDT. But accurate simulation needs to be carried out in combination with more biological modeling. Full article

Silica nanoparticles (SiNPs) are widely explored as biocompatible platforms for the delivery of photosensitizers in photodynamic therapy (PDT). In this work, porphyrins bearing amine (PNH₂) or carboxyl (PCOOH) groups were covalently conjugated onto functionalized SiNP surfaces via carbodiimide-mediated amide coupling, yielding the silica–porphyrin nanohybrids H-PNH₂ and H-PCOOH. Successful surface functionalization was confirmed by Fourier-transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. Photophysical studies demonstrated that both nanohybrids retained efficient singlet oxygen (¹O₂) generation. In vitro biological assays revealed a strong dependence of photodynamic activity on the nature of the conjugated porphyrin, with H-PCOOH exhibiting markedly enhanced photocytotoxicity with respect to the free porphyrins, while H-PNH₂ showed an attenuated light-dose response. Notably, H-PCOOH induced pronounced cell death at low light doses (1 J/cm²), with a half-maximal inhibitory concentration (IC₅₀) below 0.3 µM. These findings highlight the potential of silica–porphyrin nanohybrids as efficient photosensitizers for PDT applications. Full article

Talaporfin sodium (mono-L-aspartyl chlorin e6; NPe6), a second-generation photosensitizer, is clinically used in photodynamic therapy (PDT). It accumulates preferentially in tumors and exhibits deep tissue penetration, rapid systemic clearance, and minimal photosensitivity. However, treatment of deep-seated malignancies remains challenging. Here, we demonstrate that talaporfin sodium undergoes physicochemical reactions with X-rays to generate reactive oxygen species, a mechanism analogous to that of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX in radiodynamic therapy (RDT). To evaluate its therapeutic efficacy, we employed a pancreatic cancer xenograft model using MIA PaCa-2 cells in mice. Talaporfin sodium was administered intravenously 2 h before X-ray exposure, followed by fractionated X-ray irradiation (3 Gy daily for 3 consecutive days). Talaporfin-mediated RDT significantly inhibited tumor growth compared with radiation therapy alone. Furthermore, an exploratory RNA-seq analysis of xenografts revealed transcriptional signatures of stress and immune activation, suggesting that talaporfin-mediated RDT enhances oxidative and immunogenic responses within the tumor microenvironment. These findings highlight the potential of talaporfin sodium as a clinically translatable radiosensitizer for RDT, offering a promising strategy for the treatment of deep-seated cancers such as pancreatic carcinoma. Full article

Gadolinium (Gd)-based nanomaterials have attracted a considerable amount of attention in cancer treatment research due to their applicability in radiotherapy. However, the clinical translation of Gd-based nanomaterials is limited by their high density and poor dispersibility in aqueous media, thereby necessitating surface functionalization with biocompatible polymers. In this study, gadolinium tungstate (Gd₂(WO₄)₃) nanoflakes (GW Nfs) were functionalized with poly(glycerol) (PG) to enhance their dispersibility and stability in aqueous media. Due to their high-Z elemental composition, the GW Nfs generated reactive oxygen species (ROS) under X-ray irradiation, with improved dispersibility induced by PG functionalization further enhancing ROS productivity compared to GW Nfs. Furthermore, PG-GW loaded with the photosensitizer chlorin e6 (Ce6) demonstrated strong photocytotoxicity at Ce6 concentrations as low as 0.2 μg mL⁻¹ under light irradiation. Taken together, these results demonstrate that PG-GW/Ce6 is a promising nanomaterial for photodynamic therapy while also offering prospects for bimodal photon cancer therapy with X-rays. Full article

The efficacy of X-ray-induced photodynamic therapy (X-PDT) for deep tumors is often hindered by conventional scintillators, typically rare-earth nanoparticles plagued by long-term toxicity and suboptimal scintillation yields. Here, we introduce a copper iodide (Cu-I) cluster, Cu₂I₂(PPh₃)₂(pz), composed of earth-abundant elements, as an efficient and biocompatible energy transducer for X-PDT. A theranostic nanoplatform, CuI@PcNP, was engineered by co-encapsulating the Cu-I cluster and a phthalocyanine photosensitizer (Pc4OH) within a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2K) matrix, which confers excellent physiological stability. This nano-architecture ensures nanoscale proximity between the cluster (donor) and photosensitizer (acceptor), facilitating efficient (58%) Förster resonance energy transfer (FRET) while overcoming aggregation-induced quenching. Upon X-ray irradiation, the platform effectively converted X-rays to visible light, activating Pc4OH to generate potent reactive oxygen species (ROS) and inducing significant dose-dependent cytotoxicity in human hepatocellular carcinoma (HepG2) cells. In a murine hepatoma model, enabling image-guided X-PDT that resulted in a 77.4% tumor inhibition rate with negligible systemic toxicity. Collectively, this work pioneers the integration of phthalocyanine with Cu-I clusters, providing a stable and versatile nanoplatform for image-guided X-PDT. Full article

Hydroxypropyl methylcellulose (HPMC) is a biocompatible polymer widely used in topical formulations due to its suitable rheological behavior, film-forming capacity, and good compatibility with different active pharmaceutical ingredients. The present study demonstrates the potential of HPMC-based gels for dermal delivery of porphyrinic photosensitizers, aiming to enhance the efficiency of photodynamic therapy (PDT) in potential skin cancer applications. HPMC-based gel incorporating two previously synthesized porphyrinic photosensitizers, named 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), was developed and carefully characterized regarding its rheological behavior, texture, and in vitro activity. Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), atomic force microscopy (AFM), fluorescence, and UV-Vis spectroscopy were carried out to evaluate the structural and morphological changes induced by the incorporation of the porphyrins in the HPMC gel matrix. The gels were subsequently evaluated by pharmacotechnical analysis, including pH (7.2 for both HPMC-P2.1 and HPMC-P2.2), viscosity, spreadability, texture profile analysis, and drug content uniformity. Rheological behavior confirmed the pseudoplastic behavior, suggesting a structured system with a gel-like consistency, while physical measurements demonstrated the stability and preserved functionality of the photosensitizers within the HPMC matrix. In vitro studies revealed an efficient cellular internalization of selected porphyrins into human epidermoid carcinoma cells, a critical requirement for topical PDT applications. The study highlights the capability of HPMC gels to serve as effective delivery platforms for porphyrin-based photosensitizers, supporting their application in localized skin cancer treatment through PDT. Full article

In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of the poor penetration of visible light into tissues, which limits the efficacy of PDT in the treatment of deep-seated tumors. It is essential to optimize FRET efficiency by maximizing the overlap integral between donor emission and acceptor absorption and lengthening the duration of the donor emission. In this study, we optimized energy transfer between a scintillator (Sc) as a donor and a PS as an acceptor. Terbium (Tb) and Gadolinium (Gd) as Scs and Rose RB as a PS were chosen. The study of energy transfer between Tb, Gd and RB in solution and chelated on AGuIX NPs proved to be FRET-like. RB was conjugated directly onto AGuIX NPs (i.e., AGuIX Ln@RB), and the use of a spacer arm (i.e., AGuIX Ln@spacer arm-RB) increased FRET efficiency. Singlet oxygen production by these NPs was observed under UV–visible illumination and X-ray irradiation. The in vitro bioassay demonstrated 52% cell death of U-251MG derived from human malignant glioblastoma multiforme at a concentration of 1 μM RB after illumination and irradiation (2 Gy, 320 kV, 10 mA, 3 Gy/min at 47 cm). In addition, the RB-coupled NRP-1-targeting peptide (i.e., K(RB)DKPPR) was conjugated onto AGuIX NPs by a thiol-maleimide click chemistry reaction, and an affinity in the nM range was observed. Full article

Background/Objectives: Radiotherapy is a widely applied first-line clinical treatment modality of cancer. Copper–cysteamine (Cu-Cy) nanoparticles represent a new type of photosensitizer that demonstrates significant anti-tumor potential by X-ray-induced photodynamic therapy. Iodide is a high-Z element with superior X-ray absorption ability and has the β-decay radiotherapeutic nuclide, ¹³¹I, which emits Cherenkov light. In this study we aimed to investigate the X-ray-induced photodynamic therapy potential of iodinated Cu-Cy (Cu-Cy-I) nanoparticles and also explore the local treatment efficacy of ¹³¹I-labeled Cu-Cy-I ([¹³¹I]Cu-Cy-I) nanoparticles. Methods: The synthesis of [¹³¹I]Cu-Cy-I nanoparticles was performed with [¹³¹I]I⁻ anions. The in vitro radiobiological effects on tumor cells incubated with Cu-Cy-I nanoparticles by X-ray irradiation were investigated. The in vivo tumor growth-inhibitory effects of the combination of Cu-Cy-I nanoparticles with X-ray radiotherapy and [¹³¹I]Cu-Cy-I nanoparticles were evaluated with 4T1 tumor-xenografted mice. Results: The in vitro experiment results indicated that the X-ray irradiation with the presence of Cu-Cy-I nanoparticles produced a higher intracellular reactive oxygen species (ROS) level and more DNA damage of 4T1 cells and showed a stronger tumor cell killing ability compared to X-ray irradiation alone. The in vivo experimental results with 4T1 breast carcinoma-bearing mice showed that the combination of an intratumoral injection of Cu-Cy-I nanoparticles and X-ray radiotherapy enhanced the tumor growth-inhibitory effect and prolonged the mice’s lives. Conclusions: Cu-Cy-I nanoparticles have good potential as new radiosensitizers to enhance the efficacy of external X-ray radiotherapy. However, the efficacy of local treatment with [¹³¹I]Cu-Cy-I nanoparticles at a low ¹³¹I dose was not verified. The effective synthesis of smaller sizes of nanoparticles is necessary for further investigation of the radiotherapy potential of [¹³¹I]Cu-Cy-I nanoparticles. Full article

X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF₃) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF₃-FMN NPs has been developed, enabling the production of colloidal, spherical NPs with an approximate diameter of 100 nm, low polydispersity, and a high fluorescence quantum yield of 0.42. It has been demonstrated that CeF₃-FMN NPs exhibit pH-dependent radiation-induced redox activity when exposed to X-rays. This activity results in the generation of reactive oxygen species, which is associated with the scintillation properties of cerium and the transfer of electrons to FMN. The synthesized NPs have been demonstrated to exhibit minimal cytotoxicity towards normal cells (NCTC L929 fibroblasts) but are more toxic to tumor cells (epidermoid carcinoma A431). Concurrently, the synthesized NPs (CeF₃ and CeF₃-FMN NPs) demonstrate a pronounced selective radiosensitizing effect on tumor cells at concentrations of 10⁻⁷ and 10⁻³ M, resulting in a significant reduction in their clonogenic activity, increasing radiosensitivity for cancer cells by 1.9 times following X-ray irradiation at a dose of 3 to 6 Gy. In the context of normal cells, these nanoparticles serve the function of antioxidants, maintaining a high level of clonogenic activity. Functional nanoscintillators on the basis of cerium fluoride can be used as part of the latest technologies for the treatment of tumors within the framework of X-PDT. Full article

The Ce_0.5Y_0.35Tb_0.15F₃ nanoparticles with a CeF₃ hexagonal structure were synthesized using the co-precipitation technique. The average nanoparticle diameter was 14 ± 1 nm. The luminescence decay curves of the Ce_0.5Y_0.35Tb_0.15F₃ nanoparticles (λ_em = 541 nm, ⁵D₄–⁷F₅ transition of Tb³⁺) conjugated with Radachlorin using polyvinylpyrrolidone coating as well as without Radachlorin were detected. Efficient nonradiative energy transfer from Tb³⁺ to the Radachlorin was demonstrated. The maximum energy transfer coefficients for the nanoparticles conjugated with Radachlorin via polyvinylpyrrolidone and without the coating were 82% and 55%, respectively. The average distance between the nanoparticle surface and Radachlorin was R₀ = 4.5 nm. The best results for X-ray-induced cytotoxicity were observed for the NP-PVP-Rch sample at the lowest Rch concentration. In particular, after X-ray irradiation, the survival of A549 human lung carcinoma cells decreased by ~12%. Full article

Radiotherapy, in which X-rays are commonly used, is one of the most effective procedures for treating cancer. However, some cancer cells become resistant to radiation therapy, leading to poor prognosis. Therefore, a new therapeutic method is required to prevent cancer cells from acquiring radiation resistance. Photodynamic therapy (PDT) is a cancer treatment that uses photosensitizers, such as porphyrin compounds, and low-powered laser irradiation. We previously reported that reactive oxygen species (ROS) derived from mitochondria induce the expression of a porphyrin transporter (HCP1) and that laser irradiation enhances the cytotoxic effect. In addition, X-ray irradiation induces the production of mitochondrial ROS. Therefore, radioresistant cancer cells established with continuous X-ray irradiation would also overexpress ROS, and photodynamic therapy could be an effective therapeutic method. In this study, we established radioresistant cancer cells and examined the therapeutic effects and mechanisms with photodynamic therapy. We confirmed that X-ray-resistant cells showed overgeneration of mitochondrial ROS and elevated expression of HCP1, which led to the active accumulation of porphyrin and an increase in cytotoxicity with laser irradiation. Thus, photodynamic therapy is a promising treatment for X-ray-resistant cancers. Full article

In oncology, tremendous research has been conducted on the use of alternative minimally invasive techniques for cancer treatment and diagnosis. The use of biophotonic techniques as a standalone treatment or together with conventional imaging techniques has gained interest among researchers in recent years, while biophotonic therapies such as photothermal and photodynamic therapies tend to bring the use of non-ionizing radiation in therapy back into the spotlight due to the progressive development of optical instrumentation, enhancement agents, molecular probes, light sources and nanocarriers. Thus, the coupling of non-ionizing with ionizing radiation (IR) and the combination of nanomedicine with nuclear medicine procedures are considered to be revolutionary strategies to optimize the therapeutic efficacy of biophotonic modalities and to develop theranostic applications for the better diagnosis and treatment of cancer. Recently, the low-intensity Cerenkov light emitted by tissues as a byproduct of the IR–biostructure interaction has been suggested as an effective internal light source that can trigger phototherapy and guide radiotherapy dosimetry using Cerenkov imaging. This review also provides an overview of in vitro and in vivo studies regarding the use of Cerenkov radiation produced by X-rays or radionucleotides and combined with nanoparticles as a hybrid method to induce enhanced photothermal and photodynamic therapies. Full article

Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 (⁶⁸Ga) as an unsealed radioactive source has been proposed as an alternative strategy to X-ray-induced photodynamic therapy (X-PDT). This new strategy still aims to produce a photodynamic effect with the use of nanoparticles, namely, AGuIX. Recently, we replaced Gd from the AGuIX@ platform with Terbium (Tb) as a nanoscintillator and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) as a photosensitizer (referred to as AGuIX@Tb-P1). Although Cerenkov luminescence from ⁶⁸Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free ⁶⁸Ga could substitute X-rays of X-PDT to obtain a cytotoxic phototherapeutic effect. Results were compared with those obtained with AGuIX@Gd-P1 nanoparticles. We showed, by Monte Carlo simulations, the contribution of Tb scintillation in P1 activation by an energy transfer between Tb and P1 after Cerenkov radiation, compared to the Gd-based nanoparticles. We confirmed the involvement of the type II PDT reaction during ⁶⁸Ga-mediated Cerenkov luminescence, id est, the transfer of photon to AGuIX@Tb-P1 which, in turn, generated P1-mediated singlet oxygen. The effect of ⁶⁸Ga on cell survival was studied by clonogenic assays using human glioblastoma U-251 MG cells. Exposure of pre-treated cells with AGuIX@Tb-P1 to ⁶⁸Ga resulted in the decrease in cell clone formation, unlike AGuIX@Gd-P1. We conclude that CR-PDT could be an alternative of X-PDT. Full article