Photosensitizer Ce6 Research Articles

Oxygen-Enriched Metal-Phenolic X-Ray Nanoprocessor for Cancer Radio-Radiodynamic Therapy in Combination with Checkpoint Blockade Immunotherapy.

Radiotherapy (RT) based on DNA damage and reactive oxygen species (ROS) generation has been clinically validated in various types of cancer. However, high dose‐dependent induced toxicity to tissues, non‐selectivity, and radioresistance greatly limit the application of RT. Herein, an oxygen‐enriched X‐ray nanoprocessor Hb@Hf‐Ce6 nanoparticle is developed for improving the therapeutic effect of RT‐radiodynamic therapy (RDT), enhancing modulation of hypoxia tumor microenvironment (TME) and promoting antitumor immune response in combination with programmed cell death protein 1 (PD‐1) immune checkpoint blockade. All functional molecules are integrated into the nanoparticle based on metal‐phenolic coordination, wherein one high‐Z radiosensitizer (hafnium, Hf) coordinated with chlorin e6 (Ce6) modified polyphenols and a promising oxygen carrier (hemoglobin, Hb) is encapsulated for modulation of oxygen balance in the hypoxia TME. Specifically, under single X‐ray irradiation, radioluminescence excited by Hf can activate photosensitizer Ce6 for ROS generation by RDT. Therefore, this combinatory strategy induces comprehensive antitumor immune response for cancer eradication and metastasis inhibition. This work presents a multifunctional metal‐phenolic nanoplatform for efficient X‐ray mediated RT‐RDT in combination with immunotherapy and may provide a new therapeutic option for cancer treatment.

Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy

By incorporating an artificial reactive oxygen species (ROS) generation mechanism, a biotic/abiotic integration is designed to improve the anti-tumor effect of neutrophils by artificially potentiating their ROS effector mechanism in a remotely controlled route. Specifically, the photosensitizer Ce6 is nano-packaged by the albumin BSA to achieve biocompatible and efficient integration with neutrophils (NEs). Reinfusion of the engineered NEs into 4T1 tumor-bearing mice led to more Ce6 accumulation in tumors relative to Ce6 nanoformulation. At the peak of accumulation, tumor illumination activates the embedded Ce6 for ROS generation and NETosis formation. Because of the ROS-intensified cytolytic effect, the growth of 4T1 tumors is inhibited significantly. The photo-controlled process largely avoids the off-target effects observed frequently in current cell therapies. The strategy directly generates ROS effector molecules with spatiotemporal precision. This engineering approach is able to potentiate the native capacity of immune cells independent of the tumor microenvironment.

Tumor microenvironment triple-responsive nanoparticles enable enhanced tumor penetration and synergetic chemo-photodynamic therapy

A novel combined chemo/photodynamic therapy has been developed to use pH/ROS/MMP-2 triple-responsive drug nanocarriers for treating solid tumor with an extraordinarily high efficiency. The designed poly(ethylene glycol)-peptide-poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-3,3′-thiodipropionate) (PEG-M-PPMT) nanoparticles (NPs) encapsulating anticancer drug sorafenib (SRF) and photosensitizer chlorin e6 (Ce6) are stable in serum-containing aqueous media and can effectively accumulate in tumor as a result of the EPR effect after intravenous administration in vivo. In the presence of MMP-2 overexpressed in extracellular tumor matrix, the PEG-M-PPMT NPs can partially shed PEG corona to form smaller particles and penetrate deep into tumor tissue. After uptake by tumor cells, the acidic endosomal pH and high intracellular ROS level would trigger substantial swelling of the NPs to accelerate the drug release for rapid killing of the cancer cells. In the current combined chemo/photodynamic therapy, the intracellular ROS generation in tumor is amplified by photosensitizer Ce6 activated with external laser irradiation. As the result, the highly elevated intracellular ROS concentration can both directly induce apoptosis of ROS-stressed tumor cells and magnify acceleration of the drug release from the ROS-responsive PEG-M-PPMT NPs to gain extraordinary therapeutic efficacy. In particular, after the chemo-photodynamic therapeutic treatment with SRF/Ce6-loaded PEG-M-PPMT nanoparticles, all human lung tumors (A549) xenografted in nude mice shrank substantially with approximately 29% of the tumors being completely eradicated. Additionally, SRF/Ce6-loaded PEG-M-PPMT NPs show negligible in vivo toxicity toward major organs such as heart, liver, spleen, lung and kidney. These results demonstrate great potential of the combined chemo/photodynamic therapy based on the stimuli-responsive PEG-M-PPMT nanoparticles for efficient tumor treatment.

Polyphenol‐Based Nanomedicine Evokes Immune Activation for Combination Cancer Treatment

AbstractEngineering multifunctional nanoplatforms with high therapeutic benefits has become a promising strategy for intractable cancer treatment. A novel polyphenol‐based nanocomplex was designed to evoke highly efficacious cancer immunosurveillance while localizing therapy on the primary tumor and to minimize systemic side effects. This nanocomplex is prepared via metal–polyphenol coordination by encapsulating a natural polyphenol, gossypol, and a newly synthesized polyphenol derivative, polyethylene glycol‐Chlorin e6 (Ce6). The combination of gossypol from cotton and the photosensitizer Ce6 can induce chemotherapeutic/photodynamic immunogenic cancer cell death upon laser irradiation, which is supported by a rich maturation of dendritic cells, concentrated secretion of inflammatory cytokines, and significant inhibition of distant untreated tumors. Finally, an assistance of the programmed‐cell‐death ligand‐1 checkpoint‐blockade immunotherapy can enhance the anti‐tumor immune stimulation of our nanoplatform to a higher level.

Polyphenol-Based Nanomedicine Evokes Immune Activation for Combination Cancer Treatment.

Engineering multifunctional nanoplatforms with high therapeutic benefits has become a promising strategy for intractable cancer treatment. A novel polyphenol-based nanocomplex was designed to evoke highly efficacious cancer immunosurveillance while localizing therapy on the primary tumor and to minimize systemic side effects. This nanocomplex is prepared via metal-polyphenol coordination by encapsulating a natural polyphenol, gossypol, and a newly synthesized polyphenol derivative, polyethylene glycol-Chlorin e6 (Ce6). The combination of gossypol from cotton and the photosensitizer Ce6 can induce chemotherapeutic/photodynamic immunogenic cancer cell death upon laser irradiation, which is supported by a rich maturation of dendritic cells, concentrated secretion of inflammatory cytokines, and significant inhibition of distant untreated tumors. Finally, an assistance of the programmed-cell-death ligand-1 checkpoint-blockade immunotherapy can enhance the anti-tumor immune stimulation of our nanoplatform to a higher level.

Catalase-like nanosystem for interlocking trimodal cancer therapy with hypoxia relief

Hypoxia is a hallmark of solid tumors, and it significantly impairs the overall anticancer efficacy, particularly photodynamic therapy (PDT). Herein, a catalase-like nanovesicle with near-infrared light-responsiveness, that is, platinum/gold nanoshell encapsulated chlorin e6 (Ce6)/resveratrol (Res) liposome (Pt@Au-Ce6/Res-Lip), was developed to surmount this intractable issue. The Pt@Au-Ce6/Res-Lip can decompose overexpressed H2O2 in tumor microenvironment to produce vast amounts of O2 for further enhancement of the PDT. Under the 808 nm laser irradiation, the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells, simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res. Moreover, stimulated by 660 nm laser, numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells. With the cascade of trimodal therapeutic modality options (chemotherapy, photothermal therapy, and PDT), the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies, signifying that the Pt@Au-Ce6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.

Biodegradable Hollow Manganese Silicate Nanocomposites to Alleviate Tumor Hypoxia toward Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) has been extensively explored as a minimally invasive treatment strategy for malignant cancers. It works with the help of a photosensitizer located within cancer cells that is irradiated by near-infrared light to produce potent toxins and singlet oxygen (1O2) and induce cell death. However, reactive oxygen species can be overexpressed in tumor tissue because of the rapid metabolic activity in cancer cells, and the insufficient oxygenation (hypoxia) can lead to low production of singlet oxygen (1O2) during PDT. In this study, we developed nanocomposites composed of a hollow manganese silicate (HMnOSi) nanoparticle and a photosensitizer (Ce6) that can generate significant amounts of O2 to relieve tumor hypoxia and enhance the therapeutic efficacy of PDT. Our nanocomposites were characterized by UV-vis, fluorescence spectroscopy, transmission electron microscopy (TEM), energy-dispersive X-ray, and dynamic light scattering. Our particles' hollow mesoporous structures were shown to retain large amounts of Ce6 on the particle surface with high loading capacity (33%). TEM imaging showed that the nanoparticles could be biodegradable over time in simulated body fluid, which can imply clinical potentials. Significant H2O2 quenching capabilities to alleviate hypoxic conditions in a solid tumor were also presented. For breast cancer cells, the nanocomposite-treated group revealed that 91% of cells were dead under laser activation compared to 51% for the control group (free Ce6). In an animal study, our nanocomposites showed almost fourfold tumor growth inhibition versus the control and more than twofold over free Ce6 in orthotopic tumor xenografts. In addition, the oxygen saturation contrast inside tumors was evaluated by photoacoustic imaging to demonstrate the alleviated hypoxia in vivo. Our works provide a smart nanosystem to ameliorate the hypoxic tumor microenvironment and augment the efficacy of PDT in a targeted cancer treatment.

A Paclitaxel Prodrug Activatable by Irradiation in a Hypoxic Microenvironment.

The innate hypoxic microenvironment of most solid tumors has a major influence on tumor growth, invasiveness, and distant metastasis. Here, a hypoxia-activated self-immolative prodrug of paclitaxel (PTX2 -Azo) was synthesized and encapsulated by a peptide copolymer decorated with the photosensitizer chlorin e6 (Ce6) to prepare light-boosted PTX nanoparticle (Ce6/PTX2 -Azo NP). In this nanoparticle, PTX2 -Azo prevents premature drug leakage and realizes specific release in hypoxic tumor microenvironment and the photosensitizer Ce6 not only efficiently generates singlet oxygen under light irradiation but also acts as a positive amplifier to promote the release of PTX. The combination of photodynamic therapy (PDT) and chemotherapy results in excellent antitumor efficacy, demonstrating the great potential for synergistic cancer therapy.

A Paclitaxel Prodrug Activatable by Irradiation in a Hypoxic Microenvironment

AbstractThe innate hypoxic microenvironment of most solid tumors has a major influence on tumor growth, invasiveness, and distant metastasis. Here, a hypoxia‐activated self‐immolative prodrug of paclitaxel (PTX2‐Azo) was synthesized and encapsulated by a peptide copolymer decorated with the photosensitizer chlorin e6 (Ce6) to prepare light‐boosted PTX nanoparticle (Ce6/PTX2‐Azo NP). In this nanoparticle, PTX2‐Azo prevents premature drug leakage and realizes specific release in hypoxic tumor microenvironment and the photosensitizer Ce6 not only efficiently generates singlet oxygen under light irradiation but also acts as a positive amplifier to promote the release of PTX. The combination of photodynamic therapy (PDT) and chemotherapy results in excellent antitumor efficacy, demonstrating the great potential for synergistic cancer therapy.

A smart MnO2-doped graphene oxide nanosheet for enhanced chemo-photodynamic combinatorial therapy via simultaneous oxygenation and glutathione depletion

The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multi-functional nanosystem based on MnO2-doped graphene oxide (GO) was developed to co-load cisplatin (CisPt) and a photosensitizer (Ce6). With MnO2 doping, the nanosystem was equipped with intelligent functionalities: (1) catalyzes the decomposition of H2O2 into oxygen to relieve the tumor hypoxia; (2) depletes GSH level in tumor cells, and (3) concomitantly generates Mn2+ to proceed Fenton-like reaction, all of which contribute to the enhanced anti-tumor efficacy. Meanwhile, the surface hyaluronic acid (HA) modification could facilitate the targeted delivery of the nanosystem into tumor cells, thereby resulting in amplified cellular toxicity, as well as tumor growth inhibition in nude mice model. This work sheds a new light on the development of intelligent nanosystems for synergistic combination therapy via regulating tumor microenvironment.

Mitochondria-targeted magnetic gold nanoheterostructure for multi-modal imaging guided photothermal and photodynamic therapy of triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a type of highly aggressive cancer that is hard to be cured by the commonly used chemotherapy, mainly due to the lack of effective tumor targeting ability of the current drugs and TNBC drug resistance. Therefore, development of novel strategies for precise and high-efficient therapy of TNBCs is urgently needed. In the present work, a multifunctional magnetic gold nanoheterostructure with photosensitizer Ce6 loading (MGN@Ce6) was designed and synthesized for synergistic photothermal and photodynamic therapy (PTT/PDT) of TNBC. To improve the tumor targeting ability, cRGD and TPP cationic molecule, which can specifically target αvβ3 integrin of cancer cell membrane and mitochondria, respectively, were functionalized on the nanosystem obtaining MGN@Ce6@RT. In vitro and in vivo fluorescent imaging demonstrated that cRGD and TPP functionalization largely enhanced the delivery-efficiency of MGN@Ce6@RT into TNBC cells and tumors. Under 880 nm and 660 nm laser irradiations, MGN@Ce6@RT exhibited strong hyperthermia effect and ROS generating ability, which exerted a synergistic anti-TNBC effect by completely suppressed the tumor growth of the nude mice model. Moreover, by integrating superparamagnetic and near infrared light absorption properties into a single nanocomposite, MGN@Ce6@RT was proved to be able to realize magnetic resonance, X-ray computed tomography and photoacoustic tri-modal imaging of in vivo tumors. In all, we provide a novel strategy for precise delivery of functional nanosystems to TNBC tumors to achieve more satisfying treating outcome.

An Oxidation-Enhanced Magnetic Resonance Imaging Probe for Visual and Specific Detection of Singlet Oxygen Generated in Photodynamic Cancer Therapy In Vivo.

Singlet oxygen is regarded as the primary cytotoxic agent in cancer photodynamic therapy (PDT). Despite the advances in optical methods to image singlet oxygen, it remains a challenge for in vivo application due to the limited tissue penetration depth of light. Up to date, no singlet oxygen-specific magnetic resonance imaging (MRI) probe has been reported. Herein, a T2 -weighted MRI probe is reported to visually detect singlet oxygen generated in PDT in vitro and in vivo. The MRI probe Ce6/Fe3 O4 -M is constructed by co-encapsulation of photosensitizer Ce6 and Fe3 O4 nanoparticles in mPEG2000 -TK-C16 micelles. Thioketal (TK) linker in the probe is highly sensitive to singlet oxygen, but lowly sensitive to other reactive oxygen species (ROS) existing in physiological and pathological environments. Singlet oxygen, generated with light irradiation, triggers the cleavage of TK, which leads to loss of surface polyethylene glycol, increment of the hydrophobicity, and aggregation of Fe3 O4 nanoparticles. Subsequently, negatively enhanced T2 -weighted MRI signal is obtained for visual detection of singlet oxygen in the solution, cancer cells, and in vivo. This oxidation responsive MRI probe is expected to hold great promise in evaluating the ability of photosensitizers to generate singlet oxygen and in predicting the therapeutic efficacies of PDT in vivo.

ROS-Activatable siRNA-Engineered Polyplex for NIR-Triggered Synergistic Cancer Treatment.

Small interfering RNA (siRNA) shows excellent pharmaceutical prospects in treating diverse life-threatening diseases. Photodynamic therapy (PDT) is a clinically employed noninvasive treatment method that can trigger selective damage toward targeted tissue and cells. However, insufficient delivery of siRNA and photosensitizer to cancer cells remarkably hindered the application of siRNA and PDT in the treatment of cancer. In this study, a unique reactive oxygen species (ROS)-activatable polyplex, which consists of the PEGylated cationic polymer, ROS-cleavable linker, photosensitizer Ce6, and RRM2-against siRNA, termed PPTC/siRNA, was engineered. Upon irradiation of near-infrared (NIR) light, the polyplex efficiently generated ROS, which triggered degradation of the ROS-sensitive linker, disassembling the complex, destabilization of the cell membrane, and significantly accelerated cellular entry and endosomal escape of siRNA. Besides achieving effective siRNA internalization and gene silence in cancer cells in vitro, PPTC/siRNA synergistically inhibited tumor growth in both cell line-derived xenograft and patient-derived xenograft hepatocellular carcinoma murine models by repressing the RRM2 expression (reducing cell proliferation) and triggering photodynamic killing (enhancing cell apoptosis). The proposed polyplex also showed ideal safety profiles both in cell line and in animal. It provides a novel strategy for NIR-triggered RNAi and PDT combinational cancer treatment.

Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer

HighlightsMnO2@Ce6 nanoprobes-loaded-iPS cells (iPS-MnO2@Ce6) were developed for enhanced photodynamic and immunotherapy against cancer.Under the guidance of multi-mode real-time imaging, iPS-MnO2@Ce6 achieved an enhanced photodynamic therapeutic effect and stimulated a strong anti-tumor immune response in the tumor-bearing mouse.How to trigger strong anti-tumor immune responses has become a focus for tumor therapy. Here, we report the human-induced pluripotent stem cells (iPSs) to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy (PDT) and enhanced immunotherapy. Ce6 photosensitizer was attached on manganese dioxide (MnO2) nanoparticles, and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes. The iPS-MnO2@Ce6 actively targeted in vivo tumors, the acidic microenvironment triggered interaction between MnO2 and H2O2, released large quantities of oxygen, alleviated hypoxia in tumor. Upon PDT, singlet oxygen formed, broken iPSs released tumor-shared antigens, which evoked an intensive innate and adaptive immune response against the tumor, improving dendritic cells matured, effector T cells, and natural killer cells were activated. Meanwhile, regulatory T cells were reduced, and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6 (P < 0.05). The iPS-MnO2@Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor. Human iPSs loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.

NIR‐II Light Activated Photosensitizer with Aggregation‐Induced Emission for Precise and Efficient Two‐Photon Photodynamic Cancer Cell Ablation

AbstractNear infrared (NIR) light excitable photosensitizers are highly desirable for photodynamic therapy with deep penetration. Herein, a NIR‐II light (1200 nm) activated photosensitizer TQ‐BTPE is designed with aggregation‐induced singlet oxygen (1O2) generation for two‐photon photodynamic cancer cell ablation. TQ‐BTPE shows good two‐photon absorption and bright aggregation‐induced NIR‐I emission upon NIR‐II laser excitation. The 1O2 produced by TQ‐BTPE in an aqueous medium is much more efficient than that of commercial photosensitizer Ce6 under white light irradiation. Upon NIR‐II excitation, the two‐photon photosensitization of TQ‐BTPE is sevenfold higher than that of Ce6. The TQ‐BTPE molecules internalized by HeLa cells are mostly located in lysosomes as small aggregate dots with homogeneous distribution inside the cells, which favors efficient photodynamic cell ablation. The two‐photon photosensitization of TQ‐BTPE upon NIR‐I and NIR‐II excitation shows higher 1O2 generation efficiency than under NIR‐I excitation owing to the larger two‐photon absorption cross section at 920 nm. However, NIR‐II light exhibits better biological tissue penetration capability after passing through a fresh pork tissue, which facilitates stronger two‐photon photosensitization and better cancer cell ablation performance. This work highlights the promise of NIR‐II light excitable photosensitizers for deep‐tissue photodynamic therapy.

A multifunctional oxygen-producing MnO2-based nanoplatform for tumor microenvironment-activated imaging and combination therapy in vitro.

The current trend of cancer therapy has changed from monotherapy to synergistic or combination therapies. Among the treatment strategies, photodynamic therapy (PDT) and starvation therapy are widely employed together. However, the therapeutic effect of these treatments could lead to strong resistance and poor prognosis due to tumor hypoxia. Therefore, a smart nanoplatform (MONs-GOx@MnO2-Ce6) has been constructed herein by the assembly of glucose oxidase (GOx)-coated mesoporous organosilica nanoparticles (MONs) and MnO2 nanosheets-chlorin e6 (Ce6), which form a nanosystem. Once MONs-GOx@MnO2-Ce6 enter tumor cells, it catalyzes the oxidation of glucose using oxygen (O2) and generates hydrogen peroxide (H2O2) and gluconic acid, the former of which may accelerate the decomposition of MnO2 nanosheets. The released MnO2 nanosheets would regenerate O2 in the presence of H2O2. In this case, MnO2 nanosheets serve as (i) a nanocarrier and fluorescence quencher for the photosensitizer Ce6, (ii) a degradable material that is activated by the tumor microenvironment (TME) for fluorescence recovery, and (iii) an O2-producing carrier that reacts with H2O2 for relieving hypoxia in the tumor, which contributes to the combined starvation/photodynamic cancer therapy since these treatment strategies need O2. MONs-GOx@MnO2-Ce6 could not only realize cancer cell imaging, but also reduce intracellular glucose uptake and Glut1 expression, inhibiting the metabolism of cancer cells. This strategy shows great potential for clinical applications.

A one-pot synthesis of multifunctional Bi2S3 nanoparticles and the construction of core-shell Bi2S3@Ce6-CeO2 nanocomposites for NIR-triggered phototherapy.

As a direct thin band gap n-type semiconductor, bismuth sulfide (Bi2S3) nanomaterials possess great near-infrared (NIR)-triggered photothermal effects, photoacoustic (PA) and computed tomography (CT) imaging properties. Hence, Bi2S3 nanomaterials have become a research focal point in multiple domains, such as the construction of NIR-triggered nanosystems for cancer therapy. In this study, through a simple one-pot synthesis with the assistance of EDTA-2Na, we first obtained monodispersed spherical Bi2S3 of uniform particle sizes with fascinating photothermal and PA/CT imaging properties. Based on this, we introduced the photosensitizer Ce6 with photodynamic property and CeO2 with the O2-evolving characteristic, and thus designed a core-shell structure of the Bi2S3@Ce6-CeO2 nanocomposites (Bi2S3@Ce6-CeO2 NCs). The as-received Bi2S3@Ce6-CeO2 NCs exhibited a remarkable synergetic photothermal and photodynamic therapeutic effect both in vitro and in vivo, demonstrating its promising potential for cancer treatments. In the long term, the multifunctional PA/CT properties of both Bi2S3 NPs and Bi2S3@Ce6-CeO2 NCs in this study also supply a novel Bi2S3-based platform for constructing integrated diagnosis and treatment platforms.

Pd@Au Bimetallic Nanoplates Decorated Mesoporous MnO2 for Synergistic Nucleus-Targeted NIR-II Photothermal and Hypoxia-Relieved Photodynamic Therapy.

Bimetallic nanoparticles have received considerable attention owing to synergistic effect and their multifunctionality. Herein, new multifunctional Pd@Au bimetallic nanoplates decorated hollow mesoporous MnO2 nanoplates (H-MnO2 ) are demonstrated for achieving not only nucleus-targeted NIR-II photothermal therapy (PTT), but also tumor microenvironment (TME) hypoxia relief enhanced photodynamic therapy (PDT). The Pd@Au nanoplates present a photothermal conversion efficiency (PTCE) as high as 56.9%, superior to those PTAs activated in the NIR-II region such as Cu9 S5 nanoparticles (37%), Cu3 BiS3 nanorods (40.7%), and Au/Cu2-x S nanocrystals (43.2%). They further functionalize with transactivator of transcription (TAT) moiety for cell nuclear-targeting and biodegradable hollow mesoporous MnO2 (≈100 nm) loaded with photosensitizer Ce6 (TAT-Pd@Au/Ce6/PAH/H-MnO2 ) to construct a hierarchical targeting nanoplatform. The as-made TAT-Pd@Au/Ce6/PAH/H-MnO2 demonstrates good premature renal clearance escape ability and increased tumor tissue accumulation. It can be degraded in acidic TME and generate O2 by reacting to endogenous H2 O2 to relieve the hypoxia for enhanced PDT, while the released small TAT-Pd@Au nanoplates can effectively enter into the nucleus to mediate PTT. As a result, a remarkable therapeutic effect is achieved owing to the synergistic PTT/PDT therapy. This hierarchical targeting, TME-responsive, cytoplasm hypoxia relief PDT, and nuclear NIR-II PTT synergistic therapy can pave a new avenue for nanomaterials-based cancer therapy.

Visible light-induced apoptosis activatable nanoparticles of photosensitizer-DEVD-anticancer drug conjugate for targeted cancer therapy

The therapeutic efficacy of photodynamic therapy (PDT) in cancer treatment is attributed to the conversion of tumor oxygen into reactive singlet oxygen (1O2) using photosensitizers. However, poor tissue penetration and rapid oxygen depletion have limited the effectiveness of PDT. Therefore, we have developed visible light-induced apoptosis activatable nanoparticles of the photosensitizer (Ce6)-caspase 3 cleavable peptide (Asp-Glu-Val-Asp, DEVD)-anticancer drug monomethyl auristatin E (MMAE) conjugate, resulting in Ce6-DEVD-MMAE nanoparticles. The average size of self-assembled Ce6-DEVD-MMAE nanoparticles was 90.8 ± 18.9 nm. Compared with conventional PDT based on high-energy irradiation, the new therapy uses lower-energy irradiation to induce apoptosis of cancer cells, and activation of caspase 3 to successfully cleave the anticancer drug MMAE from the Ce6-DEVD-MMAE nanoparticles, resulting in strong cytotoxic effects in cancer cells. Notably, the one-time activation of MMAE in the Ce6-DEVD-MMAE nanoparticles further amplified the cytotoxic effect resulting in additional cell death in the absence of visible light irradiation. Furthermore, Ce6-DEVD-MMAE nanoparticles passively accumulated in the targeted tumor tissues via enhanced permeation and retention (EPR) effect in mice with squamous cell carcinoma (SCC7). The high levels of toxicity were retained after exposure to lower-energy irradiation. However, Ce6-DEVD-MMAE nanoparticles did not show any toxicity in the absence of exposure to visible light irradiation, in contrast to the toxicity of free MMAE (1–10 nM). Thus, the light-induced therapeutic strategy based on apoptotic activation of Ce6-DEVD-MMAE nanoparticles can be used to treat solid tumors inaccessible to conventional PDT.

Anti-Biofilm Property of Bioactive Upconversion Nanocomposites Containing Chlorin e6 against Periodontal Pathogens.

Photodynamic therapy (PDT) based periodontal disease treatment has received extensive attention. However, the deep tissue location of periodontal plaque makes the conventional PDT encounter a bottleneck. Herein, upconversion fluorescent nanomaterial with near-infrared light excitation was introduced into the treatment of periodontal disease, overcoming the limited tissue penetration depth of visible light in PDT. Photosensitizer Ce6 molecules were combined with upconversion nanoparticles (UCNPs) NaYF4:Yb,Er with a novel strategy. The hydrophobic UCNPs were modified with amphiphilic silane, utilizing the hydrophobic chain of the silane to bind to the hydrophobic groups of the UCNPs through a hydrophobic-hydrophobic interaction, and the Ce6 molecules were loaded in this hydrophobic layer. This achieves both the conversion of the hydrophobic to the hydrophilic surface and the loading of the oily photosensitizer molecules. Because the excitation position of the Ce6 molecule is in the red region, Mn ions were doped to enhance red light, and thus the improved PDT function. This Ce6 loaded UCNPs composites with efficient red upconversion luminescence show remarkable bacteriological therapeutic effect on Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum and the corresponding biofilms under 980 nm irradiation, indicating a high application prospect in the treatment of periodontal diseases.