Antitumor Effect Of Photodynamic Therapy Research Articles

Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy‐Upregulated Cyclooxygenase‐2

AbstractNegative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP‐Mel) are fabricated to improve photodynamic performance by inhibiting PDT‐upregulated cyclooxygenase‐2 (COX‐2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic‐K(PpIX)CGNKRTR), which can encapsulate the COX‐2 inhibitor of meloxicam. The well dispersed NP‐Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP‐Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL‐6 and TNF‐α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP‐Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

Dissolving Microneedle-Based Cascade-Activation Nanoplatform for Enhanced Photodynamic Therapy of Skin Cancer.

Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ). TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs). Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process. The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.

A design strategy of pure Type-I thiadiazolo[3,4-g]quinoxaline-based photosensitizers for photodynamic therapy

Most photosensitizers (PSs) for photodynamic therapy (PDT) can generate singlet oxygen through transferring energy with oxygen, called Type-II PSs. However, the microenvironment of solid tumor is usually anoxic. Type-I PSs can generate reactive oxygen species (ROS) through transferring electron to substrate, showing more efficient in PDT. But pure Type-I PSs are very rare. The relationship between PSs’ chemical structure and Type-I mechanism has not been explicitly stated. In this study, two thiadiazolo [3,4-g]quinoxaline (TQ) PSs (PsCBz-1 and PsCBz-2) are synthesized through introducing carbazole groups to the 4,9-position of TQ backbone. Comparing with their prototype PS, 4,9-dibrominated TQ (TQs-4), the introduction of carbazole groups reverses the reaction mechanism of PSs from pure Type-II to pure Type-I. Excitingly, the water-dispersible nanoparticles (NPs) of PsCBz-1 can achieve strong phototoxicity in vitro under both normoxia and hypoxia through Type-I mechanism. In addition, PsCBz-1 NPs also exhibits remarkable PDT antitumor effect in vivo. This study provides a feasible design strategy for pure Type-I PSs.

Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

Photodynamic therapy (PDT) has limited effects in treating metastatic breast cancer. Immune checkpoints can deplete the function of immune cells; however, the expression of immune checkpoints after PDT is unclear. This study investigates whether the limited efficacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the efficacy. A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives (HpD-PDT). The anti-tumor effect of HpD-PDT was observed, as well as CD4[Formula: see text]T, CD8[Formula: see text]T and calreticulin (CRT) by immunohistochemistry and immunofluorescence. Immune checkpoints on T cells were analyzed by flow cytometry after HpD-PDT. When combining PDT with immune checkpoint inhibitors, the antitumor effect and immune effect were assessed. For HpD-PDT at 100[Formula: see text]mW/cm2 and 40, 60 and 80[Formula: see text]J/cm2, primary tumors were suppressed and CD4[Formula: see text]T, CD8[Formula: see text]T and CRT were elevated; however, distant tumors couldn’t be inhibited and survival could not be prolonged. Immune checkpoints on T cells, especially PD1 and LAG-3 after HpD-PDT, were upregulated, which may explain the reason for the limited HpD-PDT effect. After PDT combined with anti-PD1 antibody, but not with anti-LAG-3 antibody, both the primary and distant tumors were significantly inhibited and the survival time was prolonged, additionally, CD4[Formula: see text]T, CD8[Formula: see text]T, IFN-[Formula: see text]CD4[Formula: see text]T and TNF-[Formula: see text]CD4[Formula: see text]T cells were significantly increased compared with HpD-PDT. HpD-PDT could not combat metastatic breast cancer. PD1 and LAG-3 were upregulated after HpD-PDT. Anti-PD1 antibody, but not anti-LAG-3 antibody, could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

Photodynamic Therapy for Inflammatory and Cancerous Diseases of the Intestines: Molecular Mechanisms and Prospects for Application.

Photodynamic therapy (PDT) is a minimally invasive treatment that effectively targets cancer and inflammatory diseases. It has gained recognition for its efficacy, low toxicity, and potential for repeated use. Colorectal cancer (CRC) and inflammatory bowel diseases (IBD), including Crohn's disease (CD), and ulcerative colitis (UC), impose a significant burden on global intestinal health, with increasing incidence and prevalence rates. PDT shows promise as an emerging approach for gastrointestinal disease treatment, particularly IBD and CRC. Extensive preclinical research has demonstrated the safety and effectiveness of PDT for IBD and CRC, while clinical studies are currently underway. This review provides an overview of the underlying mechanisms responsible for the anti-inflammatory and anti-tumor effects of PDT, offering insights into the clinical application of PDT in IBD and CRC treatment. It is expected that this review will serve as a valuable reference for future research on PDT for CRC and IBD, contributing to advancements in the treatment of inflammatory and cancerous diseases of the intestines.

Biomimetic photosensitizer nanocrystals trigger enhanced ferroptosis for improving cancer treatment.

As a novel non-apoptotic cell death pathway, ferroptosis can effectively enhance the antitumor effects of photodynamic therapy (PDT) by disrupting intracellular redox homeostasis. However, the reported nanocomposites that combined the PDT and ferroptosis are cumbersome to prepare, and the unfavorable tumor microenvironment also severely interferes with their tumor suppressive effects. To address this inherent barrier, this study attempted to explore photosensitizers that could activate ferroptosis pathway and found that the photosensitizer aloe-emodin (AE) could induce cellular ferroptosis based on its specific inhibiting activity to Glutathione S-transferase P1(GSTP1), a key protein for ferroptosis. Herein, we prepared AE@RBC/Fe nanocrystals (NCs) with synergistic PDT and ferroptosis therapeutic effects by one-step emulsification to obtain AE NCs cores and further modification of red blood cells (RBC) membranes and ferritin. Benefiting from the involvement of ferritin, the prepared AE@RBC/Fe NCs provide not only sufficient oxygen for oxygen-dependent PDT, but also Fe3+ for iron-dependent ferroptosis in tumor cells. Furthermore, the biomimetic surface functionalization facilitated the prolonged circulation and cancer targeting of AE@RBC/Fe NCs in vivo. The in vitro and in vivo results demonstrate that AE@RBC/Fe NCs exhibit significantly enhanced therapeutic effects for the combined two antitumor mechanisms and provide a promising prospect for achieving PDT/ferroptosis synergistic therapy.

In Vitro Anti-tumor Effects of Photodynamic Therapy on Oral Squamous Cell Carcinoma: A Review.

Introduction: Due to the increasing prevalence and high mortality rate of oral squamous cell carcinoma (OSCC) and problems with its routine treatments, more recent modalities like photodynamic therapy (PDT) have been developed. PDT effectively destroys tumor cells with minimum side effects. Research on in vitro effects of PDT may be helpful in determining the molecular mechanisms responsible for its effectiveness and can lead to the development of more efficient techniques. The aim of this study was to review the use of PDT in OSCC among in vitro studies. Methods: A literature search for English articles on PDT in OSCC was performed in PubMed, Scopus, Google Scholar, and Web of Science. Data were extracted based on the inclusion/exclusion criteria, which were detailed using the PICO framework: all eligible in vitro studies evaluating the effects of PDT on the viability of OSCC compared to controls without PDT were included. Results: Forty-one out of 567 studies were selected. The tongue was the most common OSCC site, 5-aminolevulinic acid was the most used photosensitizer (PS), cell viability/toxicity and apoptosis were the most evaluated outcomes, and lasers with wavelengths of 600-700 nm were the most common light sources and wavelengths respectively. Conclusion: PDT showed promising effects on reducing the viability of OSCC cells. Cell lines from various sources or even those originating from the same location sometimes responded differently to the same protocol. Considering the favorable results obtained from natural PSs and regarding their additional health-promoting properties, their use in future investigations with different cell lines and light specifications is recommended.

Synergic Antitumor Effect of Photodynamic Therapy and Chemotherapy Mediated by Nano Drug Delivery Systems.

This review provides a summary of recent progress in the development of different nano-platforms for the efficient synergistic effect between photodynamic therapy and chemotherapy. In particular, this review focuses on various methods in which photosensitizers and chemotherapeutic agents are co-delivered to the targeted tumor site. In many cases, the photosensitizers act as drug carriers, but this review, also covers different types of appropriate nanocarriers that aid in the delivery of photosensitizers to the tumor site. These nanocarriers include transition metal, silica and graphene-based materials, liposomes, dendrimers, polymers, metal–organic frameworks, nano emulsions, and biologically derived nanocarriers. Many studies have demonstrated various benefits from using these nanocarriers including enhanced water solubility, stability, longer circulation times, and higher accumulation of therapeutic agents/photosensitizers at tumor sites. This review also describes novel approaches from different research groups that utilize various targeting strategies to increase treatment efficacy through simultaneous photodynamic therapy and chemotherapy.

Trojan Horse-Like Nano-AIE Aggregates Based on Homologous Targeting Strategy and Their Photodynamic Therapy in Anticancer Application.

Photodynamic therapy (PDT) has become a promising candidate for cancer theranostics; however, traditional photosensitizers (PSs) usually exhibit weak fluorescence and poor reactive oxygen species (ROS) generation efficiency when aggregated. Recently, aggregation‐induced emission (AIE) luminogens have shown great potential in the development of novel PSs owing to their excellent aggregation‐induced ROS generation (AIG‐ROS) activity. However, there are still concerns that must be addressed. In this study, two near‐infrared (NIR) emitters (PI and PTI) are synthesized with AIG‐ROS characteristic. PTI exhibit a valuable redder emission with more effective intersystem crossing (ISC) process than PI. The two AIE‐active PSs show excellent lipid droplet (LD)‐specific targeting ability. The detailed therapeutic mechanism of PDT in LDs specificity is also investigated. The mechanism of oxidation of polyunsaturated fatty acids (PUFAs) in LDs to form toxic lipid peroxides (LPOs) and thereby causing cellular ferroptosis is confirmed first. Homologous targeting is also used to achieve tumor targeting via coating PSs with active cancer cell membranes. Biomimetic aggregates exhibit good targeting ability, and an improved PDT antitumor effect via AIG‐ROS activity. These findings offer a clear route to develop advanced PSs with good targeting specificity. A template has also been provided for studying the therapeutic mechanism of AIE‐active PSs.

P20-1 Enhanced Foslip® photodynamic therapy anti-tumor effect in nasopharyngeal carcinoma via fractionated light irradiation

Nasopharyngeal carcinoma (NPC) is mainly treated with chemo-radiotherapy but treatment failure was associated with drug resistance. Photodynamic therapy (PDT) is an anti-tumor treatment that combines photosensitiser (PS), visible light and molecular oxygen to induce reactive oxygen species for tumor eradication. However, limited supply of oxygen and PS in cell during light activation restricted PDT effect. Fractionated light irradiation might overcome this restriction, yet there is lacking information on the effect of fractionated light irradiation on Foslip® PDT.

Albumin-based nanoparticles combined with photodynamic therapy enhance the antitumor activity of curcumin derivative C086

C086, a derivative of curcumin, was previously identified as a novel heat shock protein 90 (Hsp90) inhibitor and was found to exhibit stronger anti-tumor activity than curcumin. However, the inferior water solubility of C086 limits both its bioavailability and therapeutic efficacy. In this study, we aimed to improve the solubility and consequently the bioavailability of C086 via the albumin-based nanoparticles (NPs). The C086-loaded human serum albumin (C086@HSA) NPs were fabricated by a simple self-assembly method. The resulting C086@HSA NPs with an average diameter size of 36 nm, combined with photodynamic therapy, showed significant cytotoxic activity against all tumor cell lines investigated along with longer duration of effect than pure C086. More investigation was carried on the anti-tumor mechanism of C086@HSA NPs, showing that its anti-tumor effect of photodynamic therapy (PDT) on human cervical carcinoma HeLa cells was associated with apoptosis and cell cycle arrest at the S and G2/M phase upon 10-min blue light illumination (450 nm, 5 mW/cm2). Furthermore, the in vivo antitumor activity of C086@HSA NPs was evaluated in 4T1 tumor-bearing mouse model using intense blue light (80 mW/cm2), confirming the enhanced antitumor activity of C086@HSA NPs through photodynamic therapy. Taken together, our work provides an efficient albumin-based nanoparticle drug delivery platform to improve the bioavailability and therapeutic efficacy of hydrophobic photosensitizers against tumor growth.

4-in-1 Fe3O4/g-C3N4@PPy-DOX nanocomposites: Magnetic targeting guided trimode combinatorial chemotherapy/PDT/PTT for cancer

At present, cancer has become a major disease threatening human health worldwide. Therefore, developing targeting guided multimode synergetic therapy has become one of the hot spots in current antitumor research and is also a great challenge. Herein, a new Fe3O4/g-C3N4@PPy-DOX nanocomposite containing magnetic iron oxide (Fe3O4) nanoparticles (NPs), lamellar structure of graphite-like carbon nitride (g-C3N4) and polypyrrole (PPy) shell with the loaded anti-tumor drug doxorubicin hydrochloride (DOX) was designed and prepared. The monodisperse Fe3O4 nanoparticles (NPs) with the diameter of 20 nm endowed the nanocomposite with the magnetic targeting ability, reducing damage to normal tissues. It is very interesting that the Fe3O4 NPs also possessed photosensitizer function for photodynamic therapy (PDT). The g-C3N4 sheets as the photocatalysis towards the degradation of water for generating O2 could effectively improve the hypoxia of solid tumors and increase the efficiency of PDT. In addition, PPy has high light-to-heat conversion efficiency, so was chosen for the cancer photothermal therapy (PTT). Finally, an anticancer drug (DOX) was loaded on the nanocomposite because the presence of mesoporous structure. Thus, the prepared Fe3O4/g-C3N4@PPy-DOX nanocomposites exhibit synergetic chemotherapy/PTT/enhanced PDT antitumor effect. This study provides an inspiration for combining targeting and multimodality to improve the anticancer efficiency.

Photodynamic therapy produces enhanced efficacy of antitumor immunotherapy by simultaneously inducing intratumoral release of sorafenib

Photodynamic therapy (PDT) can destroy local tumor cells and induce effective antitumor immune responses, and has been applied in the treatment of patients with superficial solid tumors. Numerous systemic side effects of PDT, such as pain and skin photosensitivity, however, limit this therapeutic option. In addition, the immunosuppressive tumor microenvironment has been found to be another critical barrier for the antitumor immunity induced by PDT. Therefore, effectively enhancing the cytotoxicity to tumor cells of low-dose PDT and inhibiting the tumor immunosuppressive tumor microenvironment may be a feasible strategy to overcome these drawbacks of PDT. Here, a sorafenib and chlorin e6 co-loaded reactive oxygen species (ROS)-responsive nanoparticle (NP-sfb/ce6) is developed to improve antitumor responses by intratumoral release of sorafenib at the time of PDT. Under 660-nm laser irradiation, ROS produced by chlorin e6 (ce6) destruct the nanoparticles, resulting in boosted sorafenib cascade release. The rapidly released sorafenib acts synergistically with the low-dose PDT to inhibit tumor growth by inducing strong T cell-dependent local and systemic antitumor immune responses, reprograming the tumor immune microenvironment, and limiting the interaction between cytotoxic CD8+ T cells and immunosuppressive cells. This study provides new avenues for cascade-amplifying antitumor effects of photodynamic therapy.

In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

AbstractHypoxia in the tumor microenvironment is a major hurdle dampening the antitumor effect of photodynamic therapy (PDT). Herein, active photosynthetic bacteria (Synechococcus 7942, Syne) are utilized for tumor‐targeted photosensitizer delivery and in situ photocatalyzed oxygen generation to achieve photosynthesis‐boosted PDT. Photosensitizer‐encapsulated nanoparticles (HSA/ICG) are assembled by intermolecular disulfide crosslinking and attached to the surface of Syne with amide bonds to form a biomimetic system (S/HSA/ICG). S/HSA/ICG combined the photosynthetic capability of Syne and the theranostic effect of HSA/ICG. Syne capable of photoautotrophy exhibit a moderate immune stimulation effect and a certain photodynamic role under 660 nm laser irradiation. Upon intravenous injection into tumor‐bearing mice, S/HSA/ICG can effectively accumulate in tumors and generate oxygen continuously under laser irradiation through photosynthesis, which remarkably relieve tumor hypoxia and enhance reactive oxygen species production, thereby completely eliminating primary tumors. This photosynthesis‐boosted PDT can also effectively reverse the tumor immunosuppressive microenvironment and robustly evoke systematic antitumor immune responses, which exhibit excellent effect on preventing tumor recurrence and metastasis inhibition in a metastatic triple‐negative breast cancer mouse model. Hence, this photosynthetic bacteria‐based photosynthesis‐boosted immunogenic PDT offers a promising approach to eliminate both local and metastatic tumors.

A Redox Stimulation-Activated Amphiphile for Enhanced Photodynamic Therapy.

The development of more efficient photosensitizers with minimal damage to surrounding normal tissues has been a valuable and challenging subject during photodynamic therapy (PDT). Herein, a stimuli-activated porphyrinic photosensitizer (PEG-TPP-DNB; PEG = poly(ethylene glycol); TPP = 5,10,15,20-tetraphenylporphyrin; DNB = 2,4-dinitrobenzene) with capabilities of fluorescence and, remarkably, singlet oxygen quenching was prepared successfully for photodynamic therapy with high efficiency and biosecurity. The amphiphilic PEG-TPP-DNB could be self-assembled into nanomicelles in aqueous media and dissociated in response to reductive thiol such as glutathione. Meanwhile, the fluorescence and singlet oxygen generation of porphyrinic photosensitizer would be activated to regenerate. Moreover, the intracellular uptake and localization effectively confirmed the redox-responsive and activated behavior of PEG-TPP-DNB micelles. The cytotoxicity in vitro revealed that the micelles had low dark toxicity and great phototoxicity, and in vivo bioimaging and antitumor evaluation further indicated that the micelles possessed selective tumor imaging and targeted PDT antitumor effect as well as low systemic toxicity. Overall, this tumor microenvironment-activated photosensitizer system may provide a useful strategy for precise photodynamic therapy.

MODIFICATING ACTION OF DICLOFENAC ON EFFECTS OF PHOTODYNAMIC THERAPY – IN VIVO STUDY

Introduction. Non-steroidal anti-inflammatory drugs and, in particular, diclofenac, are considered as drugs with a potentially anticarcinogenic effect and can be used to enhance the effects of antitumor therapy. Aim. To evaluate the effectiveness of diclofenac as a potential modifier of photodynamic therapy (PDT) in vivo in Ehrlich tumor model in mice. Materials and methods. The study was conducted on male mice of BALB/C strain with intradermally grafted Ehrlich carcinoma. Experimental procedures were performed on day 7 after tumor inoculation. The control group did not receive treatment, in one group only diclofenac was administered, photosensitizer was administered in three groups (photoditazin, 5 mg / kg, intravenously once), tumor was irradiated with a laser (ALOD, 662 nm) or PDT was performed, respectively, and in three groups the procedures indicated above in each case were combined with the administration of diclofenac. 2 series of experiments were conducted to assess the reproducibility of the results. The size of the tumor was recorded after exposure. Results. In the first series of the experiment, in all groups with the administration of diclofenac (45 mg/kg/day), a high animal mortality was unexpectedly observed, associated with the toxic effect of diclofenac, which required a change in its administration regime and dose (15 mg/kg) in the second series of the experiment. The administration of diclofenac did not significantly affect the efficacy of PDT, and also did not have a modifying effect in other groups (with the introduction of a photosensitizer or laser irradiation) compared with similar groups without diclofenac. PDT with photoditazine turned out to be the most effective treatment regimen: in 8 out of 10 mice in the group from the 21th day after procedure the tumors were not recorded, the animals were alive until the end of the observation for 60 days. The introduction of a photosensitizer and radiation without a photosensitizer did not lead to a significant inhibition of tumor growth. Conclusion. In vivo on a model of intradermally grafted Ehrlich tumor in mice, diclofenac does not have a modifying effect on the antitumor effects of PDT.

The photocytotoxicity effect of cationic sulfonated corrole towards lung cancer cells: in vitro and in vivo study.

Corrole is a kind of new and promising photosensitizer (PS) in cancer photodynamic therapy (PDT). However, the protein molecular mechanism of PDT activity for corrole under light irradiation is still not clear. In this paper, water-soluble cationic sulfonated corrole (1) and its metal complexes (1-Fe, 1-Mn, and 1-Cu) were prepared, and the photodynamic anti-cancer activity against various tumor cells was investigated by MTT assay. The potential molecular mechanism of PDT activity was elucidated by fluorescence microscope, flow cytometry, molecular docking, and western blotting analysis. Besides, the potential PDT anti-tumor effect of 1 in vivo was assessed in human tumor xenografts in mice. Quantitative analysis revealed that 1's phototoxicity triggered a significant generation of reactive oxygen species, causing disruption of mitochondrial membrane potential. The results of western blotting (WB) assay shown in 1's phototoxicity could induce cell apoptosis via ROS-mediated mitochondrial caspase apoptosis pathway, in which SIRT1 protein degradation played a key role. PTD activity in vivo shown in 1 could significantly reduce the growth of A549 xenografted tumor, without obvious loss of mice body weight. We clearly found that cationic sulfonated corrole is a potential candidate of PS in vitro and in vivo. The phototoxicity of 1 could induce A549 cell apoptosis by inducing ROS production increase, further to activate the mitochondrial apoptosis pathway. We concluded that SIRT1 protein is a more appropriate target in this progress.

Magnetic chitosan/graphene oxide composite loaded with novel photosensitizer for enhanced photodynamic therapy.

Photodynamic therapy (PDT) is an increasingly recognized alternative to treat various cancers in clinical practice. Most second-generation photosensitizers (PS) are hydrophobic and have poor targeting selectivity, which limit their efficacy for PDT. In this paper, graphene oxide (GO) coupled with magnetic Fe3O4 nanoparticles and chitosan (CS) (MCGO) was prepared by a one-pot solvothermal method and used as a nanocarrier for loading the new photosensitizer HNPa (λmax = 698 nm), which was first synthesized by our group, and was considered as a good water-soluble drug and an excellent tissue-penetrating agent due to its strong absorption at 698 nm (near-infrared region). The synthesized composite (MCGO–HNPa) showed high stability, good water solubility and biocompatibility, expected magnetic targetability, and good photostability for PDT even in low concentrations. Our research reveals that MCGO nanomaterials can promote the production and release of singlet oxygen (ΦΔ = 62.9%) when compared with free HNPa. In addition, the in vitro cell uptake experiments suggested that the MCGO nanomaterials can accelerate the penetration of HNPa drugs into the tumor cell nucleus and that the drug release behavior is pH-sensitive. The MTT assay results against human hepatoma cell lines HepG-2 clearly show that the MCGO–HNPa composite can effectively result in cell damage and apoptotic cell death under light, and that the nanocomposite can improve the PDT antitumor effect of PS agents with negligible dark toxicity. Meanwhile, the research on the photoreaction mechanism reveals that Type I and Type II photodynamic reactions can occur simultaneously in this PDT process, and their relative contributions depend on the type and dose of the photosensitizer. Type II has a greater effect on PDT than Type I, especially for a higher HNPa photosensitizer dose. All the results reveal the promising application of the presented novel strategy.

Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer.

Peritoneal dissemination is a major clinical issue associated with dismal prognosis and poor quality of life for patients with pancreatic cancer; however, no effective treatment strategies have been established. Herein, we evaluated the effects of photodynamic therapy (PDT) with maltotriose-conjugated chlorin (Mal3-chlorin) in culture and in a peritoneal disseminated mice model of pancreatic cancer. The Mal3-chlorin was prepared as a water-soluble chlorin derivative conjugated with four Mal3 molecules to improve cancer selectivity. In vitro, Mal3-chlorin showed superior uptake into pancreatic cancer cells compared with talaporfin, which is clinically used. Moreover, the strong cytotoxic effects of PDT with Mal3-chlorin occurred via apoptosis and reactive oxygen species generation, whereas Mal3-chlorin alone did not cause any cytotoxicity in pancreatic cancer cells. Notably, using a peritoneal disseminated mice model, we demonstrated that Mal3-chlorin accumulated in xenograft tumors and suppressed both tumor growth and ascites formation with PDT. Furthermore, PDT with Mal3-chlorin induced robust apoptosis in peritoneal disseminated tumors, as indicated by immunohistochemistry. Taken together, these findings implicate Mal3-chlorin as a potential next-generation photosensitizer for PDT and the basis of a new strategy for managing peritoneal dissemination of pancreatic cancer. Mol Cancer Ther; 16(6); 1124-32. ©2017 AACR.

Combinational anti-tumor effects of photodynamic therapy and sonodynamic therapy in breast cancer cells using in vivo studies

Combinational anti-tumor effects of photodynamic therapy and sonodynamic therapy in breast cancer cells using in vivo studies