Combination Of Photodynamic Therapy Research Articles

Research progress of photodynamic therapy in antitumor therapies

Abstract. As one of the leading causes of disease death globally, conventional treatments for cancers have been developed, including surgery, chemotherapy, radiotherapy etc. However, some drawbacks restrain their therapeutic effects. Consequently, researchers have been struggling to develop novel strategies to cure tumors. Photodynamic therapy (PDT) is a significant means that utilizes light as well as photosensitizers to kill tumor cells. In PDT, a photosensitizer absorbs a photon and transfer to states with higher energy, then energy is released and generates free radicals and ground-state molecular oxygen by two distinct types of reaction to exert therapeutic functions. This review concentrates on the antitumor principles and mechanisms of PDT, common photosensitizers, combination of PDT and other cancer therapies and its effects on several typical cancers.

Research progress of photodynamic therapy in the anti-tumor field

Abstract. Photodynamic therapy (PDT), which is based on activating photosensitizers by light of a certain wavelength to produce anti-tumor effects, has attracted much attention because of its non-invasiveness and high selectivity for tumors. In many tumor diseases with high mortality rates, PDT has achieved better therapeutic effects when combined with a variety of therapies and has become one of the most important methods for treating a variety of cancers. In this review, we have collected research on the application of PDT in cancer and its combination with chemotherapy, immunotherapy, and nanomaterials in recent years, aiming to show that the combination of PDT with other therapies deserves further exploration

Disruption of Ferroptosis Inhibition and Immune Evasion with Tumor-Activatable Prodrug for Boosted Photodynamic/Chemotherapy Eradication of Drug-Resistant Tumors.

Breast cancer is a malignant tumor that threatens the life and health of women worldwide. As the first-line chemotherapy drug for breast cancer, doxorubicin (DOX) can inhibit the synthesis of RNA and DNA, and it exhibits strong inhibitory activity against breast cancer. However, drug-induced systemic toxicity and drug resistance can occur with DOX treatment. In this work, TSPO protein is identified as a promising target for overcoming drug resistance and we designed a novel BT-DOX/PDP conjugate to solve these problems in drug chemotherapy. It is found that BT-DOX/PDP can effectively downregulate TSPO1 protein and sensitize MCF-7/Adr to DOX. Furthermore, due to its positive charge, BT-DOX/PDP is readily loaded into puerarin (PUE), the resulting BT-DOX/PDP@PUE exhibited minimal systemic toxicity but enhanced antitumor activity in animal models, as compared with BT-DOX/PDP. This study demonstrates the advantages of combined chemotherapy and photodynamic therapy in overcoming drug resistance, which may be applied in the design of other photodynamic therapy-based conjugates to enhance antitumor therapy.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid and Fractional CO2 Laser for the Management of Recalcitrant Plantar Warts

SignificancePlantar warts, benign lesions on the soles of the feet, are caused by the human papillomavirus (HPV) infecting keratinocytes. Complete eradication of these warts is challenging, often leading to recurrences. This study evaluates the combined clinical efficacy of topical 5-aminolevulinic acid (5-ALA) photodynamic therapy (PDT) and fractional carbon dioxide (CO2) laser treatment for recalcitrant plantar warts. ApproachData from 10 patients with recalcitrant plantar warts were analyzed. Initially, thickened hyperkeratotic tissue was removed using a super-pulsed CO2 laser. This was followed by fractional laser application, after which a 20% 5-ALA cream was applied occlusively for 4 hours. Patients then received He-Ne laser irradiation for 30 minutes at an energy density of 100 mW/cm², with treatments spaced 4 weeks apart. ResultsThe study included 10 participants aged 24 to 53 years (mean age: 33.4 ± 8.09 years). In total, 40 lesions were treated across 1 to 9 PDT sessions, with an average of 5.2 ± 2.86 sessions per patient. Complete clearance was achieved in 3 patients (30%), 4 patients (40%) showed an excellent response (≥80% improvement), while 2 patients had a partial response. One patient (10%) showed <50% improvement. The overall clearance rate was 70% (28 out of 40 lesions). Aside from temporary pain during the procedure and mild erythema post-treatment, one patient developed localized proliferative scarring. After a one-year follow-up, only one patient experienced recurrence. ConclusionsThe combination of 5-ALA PDT and fractional CO2 laser therapy shows promise as an effective and safe alternative for treating persistent plantar warts.

Synthesis of heavy-atom-free thienoisoindigo dye as near-infrared photosensitizer for type I photodynamic therapy and photoacoustic imaging

Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-AD) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O2-•) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy.

Combined use of 5-ALA-induced protoporphyrin IX and chlorin e6 for fluorescence diagnostics and photodynamic therapy of skin tumors.

Different types of photosensitizers (PSs) have different dynamics and intensities of accumulation, depending on the type of tumor or different areas within the same tumor. This determines the effectiveness of fluorescence diagnostics and photodynamic therapy (PDT). This paper studies the processes of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) and chlorin e6 (Ce6) accumulation in the central and border zones of a tumor after combined administration of two PSs into the patient's body. Fluorescence diagnostic methods have shown that sublingual administration of 5-ALA leads to the more intense accumulation of PpIX in a tumor compared to oral administration. Differences have been identified in the dynamics of 5-ALA-induced PpIX and Ce6 accumulation in the central and border zones of the tumor, as well as normal tissues. Ce6 accumulates mainly in the central zone of the tumor while PpIX accumulates in the border zone of the tumor. All patients with combined PDT experienced complete therapeutic pathomorphosis and relapse-free observation.

Dual-Mode Reactive Oxygen Species-Stimulated Carbon Monoxide Release for Synergistic Photodynamic and Gas Tumor Therapy.

Controllable carbon monoxide (CO) release simulated by light-generated reactive oxygen species (ROS) represents a promising approach for cancer therapy but is hampered by low CO release rate and low ROS generation of conventional photosensitizers in hypoxia tumor microenvironments. In this study, we developed a highly efficient nanoplatform (TPyNO2-FeCO NPs) through co-encapsulating organic AIE photosensitizers (PSs) and CO prodrug (Fe3(CO)12), which are capable of light-triggered robust ROS generation and CO release for synergistic photodynamic therapy (PDT) and CO gas therapy. The success of this nanoplatform leverages the design of a PS, TPyNO2, with exceptional type I and type II ROS generation capabilities, achieved through the introduction of the α-photoinduced electron transfer (α-PET) process. With the incorporation of a 4-nitrobenzyl unit as a typical PET donor, the intramolecular α-PET process not only suppresses the radiative decay to redirect the excited-state energy to intersystem crossing for more triplet-state formation but also promotes electron separation and transfer processes for radical-type ROS generation. The resultant TPyNO2 demonstrates superior singlet oxygen, superoxide anion, and hydroxyl radial generation capabilities in the aggregate state. Upon light irradiation, TPyNO2-FeCO NPs release CO via the type I and type II dual-mode ROS-mediated processes in a controlled and targeted manner, overcoming the limitations of conventional CO release systems. TPyNO2-FeCO NPs also demonstrate a self-accelerating ROS-CO-ROS loop as the released CO induces intracellular oxidative stress, depolarizes mitochondria membrane potentials, and inhibits ATP production, leading to further intracellular ROS generation. Both in vitro and in vivo experiments validated the excellent antitumor performance of the combined PDT and CO gas therapy. This study provides valuable insights into the development of advanced PSs and establishes TPyNO2-FeCO NPs as promising nanoplatforms for safe and effective antitumor applications.

Liposomal chlorin e6-mediated photodynamic therapy induces cell pyroptosis and promotes anti-tumor immune effects in breast cancer

Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE.staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches.

Study on the Synergistic Mechanism of Photodynamic Therapy Combined With Ferroptosis Inducer to Induce Ferroptosis in Cholangiocarcinoma.

Photodynamic therapy (PDT) induced lipid peroxidation reaction can lead to necrosis and apoptosis of extrahepatic cholangiocarcinoma (ECC) cells, reducing the tumor load. However, the depth of action of PDT is shallow, and its therapy efficacy is weak, making it difficult to achieve eradication even with multiple treatments. This study aims to investigate the mechanism and main pathways of ferroptosis in cholangiocarcinoma under Hematoporphyrin-mediated photodynamic therapy, and to compare the effects of different ferroptosis inducers on photodynamic therapy-induced ferroptosis in cholangiocarcinoma. To provide an experimental basis for selecting appropriate ferroptosis-inducing agents and synergizing with photodynamic therapy during the clinical perioperative period. The Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of cholangiocarcinoma cells following PDT. Flow cytometry was used to detect apoptotic cell percentage and cell cycle changes to assess the enhanced photodynamic production of reactive oxygen species (ROS) by different ferroptosis inducers, confocal imaging was used to de-assay ROS content. Western blot analysis was employed to detect the expression of GPX4 、FSP1、ASCL4 and SLC7A11. Furthermore, a fluorescence spectrophotometric assay was used to quantify the alterations in lipid peroxides (MDA, LPO, GSH, and Fe2+). The combination of PDT with Lenvatinib or Erastin resulted in increased ROS levels, and decreased GSH content, tumor cells were inhibited in the G2 phase, and the proportion of apoptotic cells increased. Additionally, GPX4, FSP1, and SLC7A11 protein expression decreased, whereas ASCL4 increased This was accompanied by heightened levels of Fe2+, LPO, and MDA. Induction of the ferroptosis pathway was observed to enhance the therapeutic efficacy of PDT. Our findings suggest that Erastin or Lenvatinib can enhance the induction of ferroptosis in cholangiocarcinoma cells by photodynamic therapy by increasing intracellular ROS and inhibiting intracellular antioxidant pathways.

Enhanced anticancer efficacy of photodynamic therapy in combination with immunotherapy

Photodynamic therapy (PDT) is known to trigger immunogenic cell death (ICD), leading to an anticancer effect even in untreated metastatic cancer, a phenomenon called the “abscopal effect”. Furthermore, ICD induction activates an immune response, which may synergize with immunotherapy. The objective of our research was to evaluate the anticancer efficacy of combining PDT with immunotherapy. To assess in vivo anticancer efficacy and the abscopal effect, we implanted CT26 cells on both flanks of BALB/c mice. The mice were categorized into five different groups: 1) PBS, 2) immunotherapy alone, 3) PDT alone, 4) immunotherapy administered 3 days after PDT, and 5) immunotherapy administered immediately after PDT. The observed antitumor effects on the primary tumor followed this order: immunotherapy administered immediately after PDT > immunotherapy administered 3 days after PDT > PDT alone > immunotherapy alone > PBS. In metastatic tumors that were not directly treated, immunotherapy administered immediately after PDT was also the most effective. In conclusion, our study confirms that the combination of PDT with immunotherapy enhances anticancer efficacy against both primary and metastatic tumors. Additionally, administering immunotherapy immediately after PDT is more effective than delayed administration.

Porphyrin-engineered nanoscale metal-organic frameworks: enhancing photodynamic therapy and ferroptosis in oncology.

Photodynamic therapy and ferroptosis induction have risen as vanguard oncological interventions, distinguished by their precision and ability to target vulnerabilities in cancer cells. Photodynamic therapy's non-invasive profile and selective cytotoxicity complement ferroptosis' unique mode of action, which exploits iron-dependent lipid peroxidation, offering a pathway to overcome chemoresistance with lower systemic impact. The synergism between photodynamic therapy and ferroptosis is underscored by the depletion of glutathione and glutathione peroxidase four inhibitions by photodynamic therapy-induced reactive oxygen species, amplifying lipid peroxidation and enhancing ferroptotic cell death. This synergy presents an opportunity to refine cancer treatment by modulating redox homeostasis. Porphyrin-based nanoscale metal-organic frameworks have unique hybrid structures and exceptional properties. These frameworks can serve as a platform for integrating photodynamic therapy and ferroptosis through carefully designed structures and functions. These nanostructures can be engineered to deliver multiple therapeutic modalities simultaneously, marking a pivotal advance in multimodal cancer therapy. This review synthesizes recent progress in porphyrin-modified nanoscale metal-organic frameworks for combined photodynamic therapy and ferroptosis, delineating the mechanisms that underlie their synergistic effects in a multimodal context. It underscores the potential of porphyrin-based nanoscale metal-organic frameworks as advanced nanocarriers in oncology, propelling the field toward more efficacious and tailored cancer treatments.

Strongly quenched activatable theranostic nanogel for precision imaging-guided photodynamic therapy and enhanced immunotherapy

Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings. In this study, we developed a near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and combined immunotherapy for rapidly growing tumors. Although NIR fluorescence and phototoxicity of NATNgel are strongly quenched, these can be selectively activated inside target tumor cells. A high tumor-to-background ratio (7.31 ± 1.40) in NIR fluorescence imaging could be achieved in NATNgel-treated mice, enabling real-time image-guided PDT. The combination of PDT and anti-PD-1 antibody therapy resulted in complete tumor regression. Histopathological evaluation of major organs and blood chemistry analysis revealed no side effects of the combined treatment regimen. In addition, the combination treatment completely suppressed the growth of rechallenged tumors. Overall, NATNgel is a safe and promising theranostic material for precision imaging-guided PDT and enhanced immunotherapy.

The Effects of Photodynamic Therapy with Low-Level Diode Laser Compared with Doxorubicin on HT-29 Colorectal Adenocarcinoma Cells Viability.

Background and Objective: Colorectal adenocarcinoma is considered one of the major causes of cancer-related lethality among other type of malignancies. Given the several limitations and adverse outcomes of conventional therapeutic regimens against colorectal cancer, the focus of many investigations has been attributed to the introduction of a novel combined regimen with harmless agents. The purpose of the present study was to investigate the effect of combined doxorubicin (DOX) treatment and photodynamic therapy (PDT) on colorectal adenocarcinoma cells. Material and Methods: HT-29 cells were exposed to different concentrations of DOX, low-level (630 nm) diode laser, and methylene blue (MB) as a photosensitizer substrate separately and a combination of them. The cytotoxic effect of the DOX, laser, MB, and their combination and the IC50 value for each treatment group were calculated by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT). The malondialdehyde (MDA) content as a biomarker of the lipid peroxidation process and liberated lactate dehydrogenase (LDH) enzyme into supernatant was determined. Results: The results of our study evidenced that a combination of photodynamic light (laser plus MB) and DOX caused a significant reduction in the percentage of HT-29 viable cells compared with control and other treatment groups. In addition, this mentioned combination led to a considerable decrease in IC50 of DOX. Increased cell membrane lipid peroxidation and cell destruction processes in the combination therapy group were proven through significant elevation of MDA content and LDH activity in the medium, respectively. Conclusion: The findings of the present study suggested that DOX combined with PDT had a better therapeutic impact on HT-29 colorectal adenocarcinoma cells. Hence, the simultaneous application of PDT along with antineoplastic drugs improves the chemosensitivity of cancerous cells via the disruption of their membrane and triggering death processes that lead to the decrease of chemotherapeutic agents required doses and undesirable effects.

Carboxymethyl chitosan-based nanoparticles of acid response for the synergistic anti-tumor effect of PDT and chemotherapy

The combination of multiple anti-tumor methods has shown significant application potential in overcoming the limitations of monotherapy. Photodynamic therapy (PDT) and chemotherapy combination is a promising strategy for reducing drug resistance and side effects. Here, inspired by the acidic environment of tumors, carboxymethyl chitosan-based pH-responsive nanovesicles were developed to co-deliver the chemotherapeutic drug doxorubicin (DOX) and photosensitizer 5-aminolevulinic acid (5-ALA). The in vitro drug release studies revealed that drugs could be responsively released when nanoparticles were triggered by the acidic environment. The controlled-release behavior improved drug retention and reduced the administration time. Our nanoparticles could significantly enhance the killing effect of drugs on tumor cells and increase intracellular levels of reactive oxygen species (ROS) compared to monotherapy, effectively achieving the effects of combined chemotherapy and PDT. The loaded DOX could kill tumor cells and the loaded 5-ALA could enhance the content of protoporphyrin IX (PpIX), resulting in excess ROS production to improve the effects of PDT. In summary, our nanoparticles could co-deliver the drugs and exert synergistical anti-tumor of PDT and chemotherapy by suppressing tumor cell proliferation and facilitating cell apoptosis.

A BODIPY-Ferrocene Conjugate for the Combined Photodynamic Therapy and Chemodynamic Therapy with Improved Antitumor Efficiency.

Photodynamic therapy (PDT) can destroy tumor cells by generating singlet oxygen (1O2) under light irradiation, which is limited by the hypoxia of the neoplastic tissue. Chemodynamic therapy (CDT) can produce toxic hydroxyl radical (⋅OH) to eradicate tumor cells by catalytic decomposition of endogenous hydrogen peroxide (H2O2), the therapeutic effect of which is highly dependent on the concentration of H2O2. Herein, we propose a BODIPY-ferrocene conjugate with a balanced 1O2 and ⋅OH generation capacity, which can serve as a high-efficiency antitumor agent by combining PDT and CDT. The ferrocene moieties endow the as-prepared conjugates with the ability of chemodynamic killing of tumor cells. Moreover, combined PDT/CDT therapy with improved antitumor efficiency can be realized after exposure to light irradiation. Compared with the monotherapy by PDT or CDT, the BODIPY-ferrocene conjugates can significantly increase the intracellular ROS levels of the tumor cells after light irradiation, thereby inducing the tumor cell apoptosis at low drug doses. In this way, a synergistic antitumor treatment is achieved by the combination of PDT and CDT.

Preparation and effects of functionalized liposomes targeting breast cancer tumors using chemotherapy, phototherapy, and immunotherapy

Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer.Graphical abstract

Experimental and clinical combined photodynamic therapy for malignant and premalignant lesions using various types of radiation

The aim of the study was to present various types of radiation that can increase the effectiveness of combined photodynamic therapy (PDT) for malignant and premalignant lesions. Material and Methods. The Web of Science, Scopus, MedLine, Library, and RSCI databases were used for finding publications on this topic, mainly over the last 10 years. Of 230 sources, 64 were included in the review. Results. Photodynamic therapy is a new cancer treatment technology that has become increasingly popular in recent years. It is often an alternative method of treating cancer when there is a high risk of side effects and complications during traditional treatments such as surgery, radiation therapy and chemotherapy. PDT requires a photosensitizer, light energy, and oxygen to create reactive oxygen species that destroy cancer cells. This review examines the basic principles and mechanisms of PDT used alone and in combination with other traditional therapies. Despite the fact that PDT is an effective and non-invasive cancer treatment, it has some limitations, such as low light penetration depth, ineffective photosensitizers and tumor hypoxia. Our study examines new strategies that use other energy sources, such as infrared- and x-rays, ultrasound, as well as electric and magnetic fields, to enhance the PDT effect and overcome its limitations. Great hopes are also associated with the use of a combination of PDT and neutron capture therapy (NСT). Currently, chlorin derivatives associated with boron carriers have been developed. They can be used for both fluorescence diagnostics and PDT, as well as for NСT. The synthesized compounds have a high selectivity of accumulation in the tumor. To date, encouraging preclinical results of high efficiency of combined use of NСT and PDT have already been obtained. Conclusion. Combination with various energy sources is a key factor for further development of PDT. Future research aimed at overcoming the limitations of PDT will contribute to unlocking the full potential of this technology in clinical practice.

Self-Assembled Nanoparticles of Silicon (IV)-NO Donor Phthalocyanine Conjugate for Tumor Photodynamic Therapy in Red Light.

The combination of photodynamic therapy (PDT) and pneumatotherapy is emerging as one of the most effective strategies for increasing cancer treatment efficacy while minimizing side effects. Photodynamic forces affect nitric oxide (NO) levels as activated photosensitizers produce NO, and NO levels in the tumor and microenvironment directly impact tumor cell responsiveness to PDT. In this paper, 3-benzenesulfonyl-4-(1-hydroxy ether)-1,2,5-oxadiazole-2-oxide NO donor-silicon phthalocyanine coupling (SiPc-NO) was designed and prepared into self-assembled nanoparticles (SiPc-NO@NPs) by precipitation method. By further introducing arginyl-glycyl-aspartic acid (RGD) on the surface of nanoparticles, NO-photosensitizer delivery systems (SiPc-NO@RGD NPs) with photo-responsive and tumor-targeting properties were finally prepared and preliminarily evaluated in terms of their formulation properties, NO release, and photosensitizing effects. Furthermore, high reactive oxygen species (ROS) generation efficiency and high PDT efficiency in two breast cancer cell lines (human MCF-7 and mouse 4T1) under irradiation were also demonstrated. The novel SiPc-NO@RGD NPs show great potential for application in NO delivery and two-photon bioimaging-guided photodynamic tumor therapy.

Hepatoma-Targeting and ROS-Responsive Polymeric Micelle-Based Chemotherapy Combined with Photodynamic Therapy for Hepatoma Treatment.

The combination of nanoplatform-based chemotherapy and photodynamic therapy (PDT) is a promising way to treat cancer. Celastrol (Cela) exhibits highly effective anti-hepatoma activity with low water solubility, poor bioavailability, non-tumor targeting, and toxic side effects. The combination of Cela-based chemotherapy and PDT via hepatoma-targeting and reactive oxygen species (ROS)-responsive polymeric micelles (PMs) could solve the application problem of Cela and further enhance antitumor efficacy. In this study, Cela and photosensitizer chlorin e6 (Ce6) co-loaded glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) PMs (Cela/Ce6/GCTR PMs) were prepared and characterized. The safety, ROS-sensitive drug release, and intracellular ROS production were evaluated. Furthermore, the in vitro anti-hepatoma effect and cellular uptaken in HepG2 and BEL-7402 cells, and in vivo pharmacokinetic, tissue distribution, and antitumor efficacy of Cela/Ce6/GCTR PMs in H22 tumor-bearing mice were then investigated. Cela/Ce6/GCTR PMs were successfully prepared with nanometer-scale particle size, favorable drug loading capacity, and encapsulation efficiency. Cela/Ce6/GCTR PMs exhibited a strong safety profile and better hemocompatibility, exhibiting less damage to normal tissues. Compared with Cela-loaded GCTR PMs, the ROS-responsiveness of Cela/Ce6/GCTR PMs was increased, and the release of Cela was accelerated after combination with PDT. Cela/Ce6/GCTR PMs can efficiently target liver tumor cells by uptake and have a high cell-killing effect in response to ROS. The combination of GCTR PM-based chemotherapy and PDT resulted in increased bioavailability of Cela and Ce6, improved liver tumor targeting, and better anti-hepatoma effects in vivo. Hepatoma-targeting and ROS-responsive GCTR PMs co-loaded with Cela and Ce6 combined with PDT exhibited improved primary hepatic carcinoma therapeutic effects with lower toxicity to normal tissues, overcoming the limitations of monotherapy and providing new strategies for tumor treatment.

The Guardian of Vision: Intelligent Bacteriophage-Based Eyedrops for Clinical Multidrug-Resistant Ocular Surface Infections.

Clinical multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is the leading cause of refractory bacterial keratitis (BK). However, the reported BK treatment methods lack biosecurity and bioavailability, which usually causes irreversible visual impairment and even blindness. Herein, for BK caused by clinically isolated MDR-PA infection, armed phages are modularized with the type I photosensitizer (PS) ACR-DMT, and an intelligent phage eyedrop is developed for combined phagotherapy and photodynamic therapy (PDT). These eyedrops maximize the advantages of bacteriophages and ACR-DMT, enabling more robust and specific targeting killing of MDR-PA under low oxygen-dependence, penetrating and disrupting biofilms, and efficiently preventing biofilm reformation. Altering the biofilm and immune microenvironments alleviates inflammation noninvasively, promotes corneal healing without scar formation, protects ocular tissues, restores visual function, and prevents long-term discomfort and pain. This strategy exhibits strong scalability, enables at-home treatment of ocular surface infections with great patient compliance and a favorable prognosis, and has significant potential for clinical application.