Photodynamic Therapy Of Cancer Research Articles

Hyaluronic acid-modified metal–organic framework for two-photon imaging-guided photodynamic therapy in triple negative breast cancer

Zr-based metal–organic frameworks (MOFs) using thiazolothiazole as an organic ligand exhibit excellent two-photon excited fluorescence performance, particularly in the generation of reactive oxygen species. In this study, a ZrTc nanoMOF was designed and modified with hyaluronic acid (HA) to provide good biocompatibility and cancer cell-specific targeting. In triple negative breast cancer (TNBC), the optimized composite ZrTc@HA exhibited considerable two-photon activity and excellent light-triggered O2·− generation ability at an excitation wavelength of 780 nm. ZrTc@HA can be used as a diagnostic probe for fluorescence imaging and as a therapeutic agent for photodynamic therapy (PDT) with no remarkable toxicity in vitro or in a subcutaneous tumor model in vivo. In summary, we developed a promising two-photon-activated ZrTc@HA for PDT in TNBC, with immense potential for advancements in monotherapy and synergistic phototherapy.

Photodynamic Therapy for Colorectal Cancer: An Update and a Look to the Future.

This review provides an update on the current state of photodynamic therapy (PDT) for colorectal cancer (CRC) and explores potential future directions in this field. PDT has emerged as a promising minimally invasive treatment modality that utilizes photosensitizers and specific light wavelengths to induce cell death in targeted tumor tissues. In recent years, significant progress has been made in understanding the underlying mechanisms, optimizing treatment protocols, and improving the efficacy of PDT for CRC. This article highlights key advancements in PDT techniques, including novel photosensitizers, light sources, and delivery methods. Furthermore, it discusses ongoing research efforts and potential future directions, such as combination therapies and nanotechnology-based approaches. By elucidating the current landscape and providing insights into future directions, this review aims to guide researchers and clinicians in harnessing the full potential of PDT for the effective management of CRC.

Design and Synthesis of BODIPY-Hetero[5]helicenes as Heavy-Atom-Free Triplet Photosensitizers for Photodynamic Therapy of Cancer.

Designing heavy-atom-free triplet photosensitizers (PSs) is a challenge for the efficient photodynamic therapy (PDT) of cancer. Helicenes are twisted polycyclic aromatic hydrocarbons (PAHs) with an efficient intersystem crossing (ISC) that is proportional to their twisting angle. But their difficult syntheses and weak absorption profile in the visible spectral region restrict their use as heavy-atom-free triplet PSs for PDT. On the other hand, boron-containing PAHs, BODIPYs are highly recognized for their outstanding optical properties. However, planar BODIPY dyes has low ISC and thus they are not very effective as PDT agents. We have designed and synthesized fused compounds containing both BODIPY and hetero[5]helicene structures to develop red-shifted chromophores with efficient ISC. One of the pyrrole units of the BODIPY core was also replaced by a thiazole unit to further enhance the triplet conversion. All the fused compounds have helical structure, and their twisting angles are also increased by substitutions at the boron centre. The helical structures of the BODIPY-hetero[5]helicenes were confirmed by X-ray crystallography and DFT structure optimization. The designed BODIPY-hetero[5]helicenes showed superior optical properties and high ISC with respect to [5]helicene. Interestingly their ISC efficiencies increase proportionally with their twisting angles. This is the first report on the relationship between the twisting angle and the ISC efficiency in twisted BODIPY-based compounds. Theoretical calculations showed that energy gap of the S1 and T1 states decreases in BODIPY-hetero[5]helicene as compared to planar BODIPY. This enhances the ISC rate in BODIPY-hetero[5]helicene, which is responsible for their high generation of singlet oxygen. Finally, their potential applications as PDT agents were investigated, and one BODIPY-hetero[5]helicene showed efficient cancer cell killing upon photo-exposure. This new design strategy will be very useful for the future development of heavy-atom-free PDT agents.

Furin Enzyme-Responsive siRNA Delivery System for Efficient Anti-Hypoxia-Assisted Cancer Photodynamic Therapy

Furin Enzyme-Responsive siRNA Delivery System for Efficient Anti-Hypoxia-Assisted Cancer Photodynamic Therapy

Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques.

Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms of phthalocyanines for therapeutic applications. In the current work, polyvinylpyrrolidone (PVP) and micellar formulations were compared for encapsulating and monomerizing a water-soluble zinc phthalocyanine bearing four non-peripheral triethylene glycol chains (Pc1). 1H NMR spectroscopy combined with UV-vis absorption and fluorescence spectroscopy revealed that Pc1 exists as a mixture of regioisomers in monomeric form in dimethyl sulfoxide but forms dimers in an aqueous buffer. PVP, polyethylene glycol castor oil (Kolliphor RH40), and three different triblock copolymers with varying proportions of polyethylene and polypropylene glycol units (termed P188, P84, and F127) were tested as micellar carriers for Pc1. 1H NMR chemical shift analysis, diffusion-ordered spectroscopy, and 2D nuclear Overhauser enhancement spectroscopy was applied to monitor the encapsulation and localization of Pc1 at the polymer interface. Kolliphor RH40 and F127 micelles exhibited the highest affinity for encapsulating Pc1 in the micellar core and resulted in intense Pc1 fluorescence emission as well as efficient singlet oxygen formation along with PVP. Among the triblock copolymers, efficiency in binding and dimer dissolution decreased in the order F127 > P84 > P188. PVP was a strong binder for Pc1. However, Pc1 molecules are rather surface-attached and exist as monomer and dimer mixtures. The results demonstrate that NMR combined with optical spectroscopy offer powerful tools to assess parameters like drug binding, localization sites, and dynamic properties that play key roles in achieving high host-guest compatibility. With the corresponding adjustments, polymeric micelles can offer simple and easily accessible drug delivery systems optimizing phthalocyanines' properties as efficient photosensitizers.

T4 Phage Display Technology for Enhanced Photodynamic Therapy of Breast Cancer

T4 Phage Display Technology for Enhanced Photodynamic Therapy of Breast Cancer

Photodynamic Therapy of Breast Cancer in Animal Models and Their Potential Use in Clinical Trials-Role of the Photosensitizers: A Review.

In this article, we reviewed the use of photodynamic therapy (PDT) for breast cancer (BC) in animal models. These in vivo models imitate the cancer disease progression, aid diagnosis, as well as create opportunities to assess treatment during the approval process for the new drug. BC ranks first among women's cancers. Nowadays, there are many diagnostic methods and therapy options for BC but the majority of them have severe side effects. This article discusses the advantages and some disadvantages of the use of small and large animals used for BC models. A literature review showed that the majority of studies have used large animal models, and recently there has been more interest in developing BC in small animal models. BC cell lines such as MCF-7, BT-474, MDA-MB-231, and 4T1 are commercially available for two-dimensional and three-dimensional in vitro cell cultures and subcutaneous models. The purpose of this article is to discuss the performance of PDT in animal models and its further clinical implications. PDT is known to be a non-invasive therapy, which uses monochromatic light and energy to excite photosensitizers (PSs) for the generation of reactive oxygen species as the required factors. Herein, we discuss the use of five photosensitizers in BC models such as chlorin e6 (Ce6), methylene blue, indocyanine green, 5-aminolevulinic acid, and meta-tetra(hydroxyphenyl)chlorin. The database PubMed and Scopus were searched for keywords: 'photodynamic therapy', 'breast cancer', 'animal model', 'clinical studies', and 'photosensitizer(s)'. The PDT search results in animal experiments and its effect on a living organism indicate the possibility of its application in clinical trials on women with local and disseminated BC. The availability and accessibility of small and large BC animal models enable the progress and trial of cancer drugs for innovative technologies and new diagnostics and treatments.

Highly Efficient Photosensitizers with Molecular Vibrational Torsion for Cancer Photodynamic Therapy.

The development of highly effective photosensitizers (PSs) for photodynamic therapy remains a great challenge at present. Most PSs rely on the heavy-atom effect or the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) effect to promote ISC, which brings about additional cytotoxicity, and the latter is susceptible to the interference of solvent environment. Herein, an immanent universal property named photoinduced molecular vibrational torsion (PVT)-enhanced spin-orbit coupling (PVT-SOC) in PSs has been first revealed. PVT is verified to be a widespread intrinsic property of quinoid cyanine (QCy) dyes that occurs on an extremely short time scale (10-10 s) and can be captured by transient spectra. The PVT property can provide reinforced SOC as the occurrence of ISC predicted by the El Sayed rules (1ππ*-3nπ*), which ensures efficient photosensitization ability for QCy dyes. Hence, QTCy7-Ac exhibited the highest singlet oxygen yield (13-fold higher than that of TCy7) and lossless fluorescence quantum yield (ΦF) under near-infrared (NIR) irradiation. The preeminent photochemical properties accompanied by high biosecurity enable it to effectively perform photoablation in solid tumors. The revelation of this property supplies a new route for constructing high-performance PSs for achieving enhanced cancer phototherapy.

Investigation of Postoperative Delirium and Subsyndromal Delirium in Photodynamic Therapy (PDT) for Esophageal Cancer with Laserphyrin

Investigation of Postoperative Delirium and Subsyndromal Delirium in Photodynamic Therapy (PDT) for Esophageal Cancer with Laserphyrin

From cell membrane to mitochondria: Time-dependent AIE photosensitizer for fluorescence imaging and photodynamic anticancer therapy

Aggregation-induced emission photosensitizers (AIE-PSs) targeting different subcellular organelles with time-dependent manner are highly promising for clinical applications but rarely reported. Herein, we designed and synthesized the near-infrared (NIR) emission AIE-PS (CTQ-S) with broad absorption and excellent type I reactive oxygen species (ROS) generation efficiency that was superior to the widely used PS (Rose Bengal and Chlorine 6). With short-term incubation, CTQ-S anchored on the cell membrane (Rr: 0.843, Rr is for Pearson correlation coefficient) and gradually entered the mitochondria (Rr: 0.937) of cancer cells, showing excellent time-dependent fluorescence fluorescent imaging effect. Furthermore, CTQ-S realized the selective photodynamic therapy (PDT) effect in a time-dependent manner under white light irradiation. This work provided a new way for cancer cells fluorescence imaging and PDT.

Nanoscale Multivariate Metal–Organic Frameworks Amplify Oxidative Stress for Efficient Photodynamic Therapy of Cancer

Nanoscale Multivariate Metal–Organic Frameworks Amplify Oxidative Stress for Efficient Photodynamic Therapy of Cancer

Photophysics of Glycosylated Ring‐Fused Chlorin Complexes and Their Photosensitizing Effects on Cancer Cells

AbstractThe future of photodynamic therapy (PDT) as a promising cancer treatment relies on the development of new selective and effective photosensitizers (PS) with improved photophysical and biochemical qualities. Herein, we present the synthetic procedure, photophysical properties and photosensitizing effects of novel glycosylated 4,5,6,7‐tetrahydropyrazolo[1,5‐a]pyridine] fused chlorin agents featuring either glucose, galactose, or N‐acetyl glucosamine. It is shown that both the proto‐ and Zn2+‐ion forms of the ring‐stabilized glycochlorins exhibit the required photophysical properties in terms of triplet excited states and singlet oxygen generation, the latter more than 50 % in organic solvents such as CHCl3. Employing the rat AY‐27 and human T24 cancer cell models, it was found that these are superior to the corresponding unglycosylated chlorin in biological activity, and moreover, the proto form is 2–3 times superior to the Zn‐stabilized variant. Provisional flow cytometry and cell localization studies of the proto‐form indicate both necrotic and apoptotic biological activity, and that the photosensitizer localizes in the mitochondria, cell membrane and lysosomes. However, the localization into the lysosomes is dominating and increases substantially with time. We anticipate the findings will aid in the development of photosensitizers for targeted cancer PDT.

Photodynamic Therapy of Oral Cancer and Novel Liposomal Photosensitizers

Photodynamic therapy facilitates the selective destruction of cancer tissue by utilizing a photosensitizer drug, the light near the absorbance wavelength of the drug, and oxygen. Methylene Blue, 5-aminolevulinic acid (the precursor of the photosensitizer, protoporphyrin IX), porphyrin, Foscan, Chlorin e6, and HPPH have been used successfully as photosensitizers in the treatment of oral verrucous hyperplasia, oral leukoplakia, oral lichen planus, and head and neck squamous cell carcinoma. “Theranostic” liposomes can deliver a contrast agent for magnetic resonance imaging and a photosensitizer for the image-guided photodynamic therapy of head and neck cancer. Liposomes incorporating photosensitizers can be targeted to cell surface markers overexpressed on cancer cells. Novel porphyrinoids have been developed in our laboratories that are highly effective as photosensitizers. Tribenzoporphyrazines encapsulated in cationic liposomes have produced IC50 values up to 50 times lower compared to the free photosensitizers. It is anticipated that targeting these drugs to cancer stem cells, using upconversion nanoparticles for the near-infrared irradiation of tumors to activate the photosensitizers, and overcoming tumor hypoxia will enhance the efficacy of photodynamic therapy of tumors accessible to light sources.

Internalization-Responsive Poly(lactic-co-glycolic acid) Nanoparticles for Image-Guided Photodynamic Therapy against HER2-Positive Breast Cancer

Oncotheranostic nanoagents are powerful artificial tools that significantly outperform traditional antitumor therapies. Among the wide variety of nanoagents, poly(lactic-co-glycolic acid) (PLGA) nanoparticles have proven to be one of the most successful candidates for translation into clinical practice. Here, we present PLGA nanoparticles for HER2-targeted diagnostic and photodynamic therapy with proven efficacy in vivo. Namely, we developed an oncotheranostic platform that is based on PLGA nanoparticles and possesses red/green light dual-activated diagnostic/therapeutic properties for HER2-targeted photodynamic therapy of aggressive breast cancer. PLGA nanoparticles were loaded with a red light-activated dye Nile Blue with pronounced solvatochromic properties for diagnostic applications and with a green light-activated photodynamic sensitizer Rose Bengal for photodynamic therapy. Targeted delivery was ensured by the noncovalent decoration of nanoparticles with anti-HER2 antibodies, which can be readily adapted for large-scale biotechnological production. In vitro and in vivo studies proved the effectiveness of red light-mediated HER2-specific imaging and green light-induced cytotoxicity of anti-HER2 PLGA. Interestingly, these particles fluoresced only after cellular internalization, which minimizes background signals inside the organism, thus facilitating real-time diagnostics. The particles allowed efficient and selective visualization of the HER2-positive primary tumor node and metastases spread and led to complete remission in BALB/c Nu/Nu mice with the HER2-positive xenografts after a single session of photodynamic therapy.

Biocompatible Aza-BODIPY-Biotin Conjugates for Photodynamic Therapy of Cancer.

With an objective to develop efficient photosensitizers to cancerous tissues, we synthesized two novel biocompatible sensitizers based on aza-BODIPYs incorporated with heavy atoms and biotin moieties. The bioconjugates DPR2a and DPR2b exhibited a favorable absorption range (600-750 nm) with excellent triplet-state quantum yields (up to 79%) and singlet oxygen generation yields (up to 75%). In vitro photobiological investigations employing MDA-MB-231 breast cancer cell lines exhibited rapid cellular uptake, negligible dark toxicity, and high photocytotoxicity. The mechanism of cell death of these systems was predominantly due to the mitochondrial damage, leading to apoptosis mediated via the generation of singlet oxygen-triggered reactive oxygen species. The in vivo studies with the representative conjugate DPR2a employing female NOD/SCID mice models showed inhibition in tumor growth and significantly decreased tumor volume post photodynamic therapy (PDT) treatment. Our results validate that both DPR2a and DPR2b with iodine incorporation exhibit favorable and superior photophysical and photobiological aspects and demonstrate thereby their potential applications in imaging and PDT of cancer.

Shining a Light on Prostate Cancer: Photodynamic Therapy and Combination Approaches.

Prostate cancer is a major health concern worldwide, and current treatments, such as surgery, radiation therapy, and chemotherapy, are associated with significant side effects and limitations. Photodynamic therapy (PDT) is a promising alternative that has the potential to provide a minimally invasive and highly targeted approach to treating prostate cancer. PDT involves the use of photosensitizers (PSs) that are activated by light to produce reactive oxygen species (ROS), which can induce tumor cell death. There are two main types of PSs: synthetic and natural. Synthetic PSs are classified into four generations based on their structural and photophysical properties, while natural PSs are derived from plant and bacterial sources. Combining PDT with other therapies, such as photothermal therapy (PTT), photoimmunotherapy (PIT), and chemotherapy (CT), is also being explored as a way to improve its efficacy. This review provides an overview of conventional treatments for prostate cancer, the underlying principles of PDT, and the different types of PSs used in PDT as well as ongoing clinical studies. It also discusses the various forms of combination therapy being explored in the context of PDT for prostate cancer, as well as the challenges and opportunities associated with this approach. Overall, PDT has the potential to provide a more effective and less invasive treatment option for prostate cancer, and ongoing research is aimed at improving its selectivity and efficacy in clinical settings.

Recent progress on near-infrared fluorescence heptamethine cyanine dye-based molecules and nanoparticles for tumor imaging and treatment.

Recenly, near-infrared fluorescence heptamethine cyanine dyes have shown satisfactory values in bioengineering, biology, and pharmacy especially in cancer diagnosis and treatment, owing to their excellent fluorescence property and biocompatibility. In order to achieve broad application prospects, diverse structures, and chemical properties of heptamethine cyanine dyes have been designed to develop novel functional molecules and nanoparticles over the past decade. For fluorescence and photoacoustic tumor imaging properties, heptamethine cyanine dyes are equipped with good photothermal performance and reactive oxygen species production properties under near-infrared light irradiation, thus holding great promise in photodynamic and/or photothermal cancer therapies. This review offers a comprehensive scope of the structures, comparisons, and applications of heptamethine cyanine dyes-based molecules as well as nanoparticles in tumor treatment and imaging in current years. Therefore, this review may drive the development and innovation of heptamethine cyanine dyes, significantly offering opportunities for improving tumor imaging and treatment in a precise noninvasive manner. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

CD44-mediated tumor homing of hyaluronic acid nanogels for hypoxia-activated photodynamic therapy against tumor

In this study, unique hypoxia-activated hyaluronic acid nanogels (HANGs) were reported for CD44-targeted delivery of photosensitizers (chlorin e6, Ce6) for diagnostic imaging and photodynamic therapy (PDT) of cancers. Through the use of a hypoxia-responsive cross-linker (AZO-CDI), the HANGs were prepared by chemically cross-linking primary amine groups-functionalized hyaluronic acid (HA). Under normoxic condition, fluorescence of Ce6 conjugated on the HANGs was highly quenched, and level of reactive oxygen species (ROS) generated from the HANGs was rather low after laser irradiation. However, under hypoxic condition, the HANGs underwent rapid disassociation, and fluorescence of Ce6 conjugated on the HANGs was recovered, triggering high-level singlet oxygen generation after laser irradiation. Due to the presence of HA, the HANGs showed much higher cellular uptake by CD44-positive cancer cells (A549 cells) than that by CD44-negative cancer cells (HepG2 cells). In addition, the HANGs could generate higher level of ROS in A549 cells because of improved cancer cell uptake. This excellent tumor-targeting and singlet oxygen-generating ability of the HANGs was favorable to hypoxia-activated PDT of CD44-positive cancers with significant inhibition of tumor growth within the whole treatment period. Taken together, the HANGs are safe and effective tools in treating CD44-positive cancers.

Synthesis of Heavy-Atom-Free Triplet Photosensitizers Based on Organoboron Complexes

AbstractA new class of organoboron complexes have been developed as heavy-atom-free triplet photosensitizers. A methodology was developed for the synthesis of an indolocarbazole–imine boron difluoride (IIBD) dye and its dimer from a 6-formylindolocarbazole. The IIBD dye was then coupled with a BODIPY dye through the C-2 or C-8 position of the latter to synthesize two dyads. Both dyads showed superior photophysical properties to those of the IIBD dyes. The relative triplet conversion efficiencies of these dyes were determined by measuring their singlet-oxygen (1O2) generation capacities. All the synthesized dyes showed high 1O2 generation compared with the BODIPY dye PM567. The dyad linked through the C-2 position of the BODIPY core showed the highest 1O2 generation efficiency, which could be useful for photodynamic therapy of cancers.

Mesenchymal Stem Cell Membrane-Coated TPCS2a-Loaded Nanoparticles for Breast Cancer Photodynamic Therapy.

Despite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because of its selectivity and low off-target effects. However, the hydrophobicity of photosensitizers (PSs) impairs their solubility and limits the circulation in the bloodstream, thus representing a major challenge. The use of polymeric nanoparticles (NPs) to encapsulate the PS may represent a valuable strategy to overcome these issues. Herein, we developed a novel biomimetic PDT nanoplatform (NPs) based on a polymeric core of poly(lactic-co-glycolic)acid (PLGA) loaded with the PS meso-tetraphenylchlorin disulfonate (TPCS2a). TPCS2a@NPs of 98.89 ± 18.56 nm with an encapsulation efficiency percentage (EE%) of 81.9 ± 7.92% were obtained and coated with mesenchymal stem cells-derived plasma membranes (mMSCs) (mMSC-TPCS2a@NPs, size of 139.31 ± 12.94 nm). The mMSC coating armed NPs with biomimetic features to impart long circulation times and tumor-homing capabilities. In vitro, biomimetic mMSC-TPCS2a@NPs showed a decrease in macrophage uptake of 54% to 70%, depending on the conditions applied, as compared to uncoated TPCS2a@NPs. Both NP formulations efficiently accumulated in MCF7 and MDA-MB-231 BC cells, while the uptake was significantly lower in normal breast epithelial MCF10A cells with respect to tumor cells. Moreover, encapsulation of TPCS2a in mMSC-TPCS2a@NPs effectively prevents its aggregation, ensuring efficient singlet oxygen (1O2) production after red light irradiation, which resulted in a considerable in vitro anticancer effect in both BC cell monolayers (IC50 < 0.15 µM) and three-dimensional spheroids.