Chlorin E6 Research Articles

Manganese-coordinated nanoparticle with high drug-loading capacity and synergistic photo-/immuno-therapy for cancer treatments

Stimulator of interferon genes (STING) agonists have shown promise in cancer treatment by stimulating the innate immune response, yet their clinical potential has been limited by inefficient cytosolic entry and unsatisfactory pharmacological activities. Moreover, aggressive tumors with “cold” and immunosuppressive microenvironments may not be effectively suppressed solely through innate immunotherapy. Herein, we propose a multifaceted immunostimulating nanoparticle (Mn-MC NP), which integrates manganese II (Mn2+) coordinated photosensitizers (chlorin e6, Ce6) and STING agonists (MSA-2) within a PEGylated nanostructure. In Mn-MC NPs, Ce6 exerts potent phototherapeutic effects, facilitating tumor ablation and inducing immunogenic cell death to elicit robust adaptive antitumor immunity. MSA-2 activates the STING pathway powered by Mn2+, thereby promoting innate antitumor immunity. The Mn-MC NPs feature a high drug-loading capacity (63.42 %) and directly ablate tumor tissue while synergistically boosting both adaptive and innate immune responses. In subsutaneous tumor mouse models, the Mn-MC NPs exhibit remarkable efficacy in not only eradicating primary tumors but also impeding the progression of distal and metastatic tumors through synergistic immunotherapy. Additionally, they contribute to preventing tumor recurrence by fostering long-term immunological memory. Our multifaceted immunostimulating nanoparticle holds significant potential for overcoming limitations associated with insufficient antitumor immunity and ineffective cancer treatment.

Abstract We113: Intravascular Theranostic Photoactivation Guided By OCT-NIRF Dual-Modal Imaging Facilitates Inflammation Resolution of High-Risk Plaque

Introduction and Hypothesis: Photoactivation eliminates inflammatory cells and promotes healing, paving the way for atherosclerosis intervention. We hypothesized that intravascular macrophage-targeted near-infrared fluorescence (NIRF) emitting photoactivation could facilitate inflammation resolution and stabilize the inflamed high-risk plaques. Method and Results: We newly fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the NIRF-emitting photosensitizer chlorin e6 (Ce6) and the Dectin-1 ligand laminarin (LAM-Ce6). By intravascular OCT-NIRF structural-molecular imaging at 0- vs 4 weeks, LAM-Ce6 under light irradiation through a customized intravascular fiber effectively attenuated inflammatory NIRF signals, resulting in replacement of fibrotic composition in the targeted plaques (Figure A, P <0.01). Mechanistically, one hour after the light irradiation, autophagy was strongly augmented with the formation of autophagolysosomes (Figure B, P <0.001) and an increase of CD206-positive cells at 7 days. Furthermore, TUNEL/RAM11- and CD206/MerTK-positive cells were prominently increased at 1 day, suggestive of enhanced efferocytosis in the treated plaques (Figure C, the white arrow: macrophage associated apoptotic cells, P <0.05). In line with inflammation resolution, photoactivation enhanced the cholesterol efflux regulatory protein ABCA1 and induced TGF-β in macrophages, which subsequently stimulated smooth muscle cells and produced collagen within the lesions (Figure D). Conclusions: The macrophage Dectin-1 targetable intravascular photoactivation assisted by OCT-NIRF catheter imaging could ultimately transit the plaque phenotype to collagen-rich fibrotic one by autophagy-mediated inflammation resolution with a fibrotic replacement. This novel targeted photoactivation is expected to offer new opportunity for the catheter-based theranostic strategy in patients with macrophage/lipid-rich inflamed coronary plaques.

Photodynamic therapy with methylene blue and chlorin e6 photosensitizers: study on Ehrlich carcinoma mice model

Hypoxia negatively affcts the effctiveness of all types of anticancer therapy, in particular photodynamic therapy (PDT). In this regard, various approaches to overcome the limitations associated with hypoxia are widely discussed in the literature, one of them is the use of photosensitizers (PS) operating through the fist mechanism of the photodynamic reaction, such as methylene blue (MB). Previously, we have demonstrated that MB can have a positive effect on tumor oxygenation. In this work, we investigated the photodynamic activity of MB and a combination of MB with chlorin e6 on a tumor in vivo using a model of Ehrlich carcinoma. PDT was studied with the joint and separate administration of chlorin e6 and MB. The accumulation and localization of MB and its combination with chlorin e6 in vivo was assessed using video ˛uorescence and spectroscopic methods, and the effect of laser exposure on accumulation was analyzed. After the PDT with chlorin e6, MB and a combination of MB with chlorin e6, a good therapeutic effect and a decrease in the tumor growth rate were observed compared to the control, especially in groups with PDT with MB and with the simultaneous administration of chlorin e6 and MB. The level of tumor oxygenation on days 3 and 5 after PDT was higher for groups with irradiation, the highest oxygenation on the 5th day after PDT was observed in the group with PDT only with MB. Phasor diagrams of tumors after PDT show a deviation from the metabolic trajectory and a shift towards a longer lifetimes compared to the control tumor, which indicates the presence of lipid peroxidation products. Thus, tumor regression after PDT is associated with the direct destruction of tumor cells under the in˛uence of reactive oxygen species formed during PDT. Thus, the effectiveness of PDT with the combined use of MB and chlorin e6 has been demonstrated, and the main mechanisms of the antitumor effect of the combination of these PS have been studied.

Carrier-Free Photodynamic Bioregulators Inhibiting Lactic Acid Efflux Combined with Immune Checkpoint Blockade for Triple-Negative Breast Cancer Immunotherapy.

Abnormal tumor metabolism creates a complex tumor immune microenvironment that plays a dominant role in the metastasis of triple-negative breast cancer (TNBC). TNBC is insensitive to immune checkpoint blockade (ICB) therapy because of insufficient cytotoxic T lymphocyte (CTL) infiltration and a hyper-lactic acid-suppressive immune microenvironment caused by abnormal glycolysis. Herein, we propose an amplified strategy based on lactic acid regulation to reprogram the immunosuppressive tumor microenvironment (ITM) and combine it with ICB therapy to achieve enhanced antitumor immunotherapy effects. Specifically, we constructed CASN, a carrier-free photodynamic bioregulator, through the self-assembly of the photosensitizer Chlorin e6 and monocarboxylate transporter 1 (MCT1) inhibitor AZD3965. CASN exhibited a uniform structure, good stability, and drug accumulation at the tumor site. CASN-mediated photodynamic therapy following laser irradiation inhibited primary tumor growth and induced immunogenic cell death. Furthermore, CASN reduced lactic acid-mediated regulatory T cell generation and M2 tumor-associated macrophage polarization by blocking MCT1-mediated lactic acid efflux to attenuate immune suppression, inducing the recruitment and activation of CTLs. Ultimately, CASN-mediated immunopotentiation combined with ICB therapy considerably strengthened tumor immunotherapy and effectively inhibited tumor growth and metastasis of TNBC. This synergistic amplification strategy overcomes the limitations of an acidic ITM and presents a potential clinical treatment option for metastatic tumors.

Supramolecular self-sensitized dual-drug nanoassemblies potentiating chemo-photodynamic therapy for effective cancer treatment

Chemo-photodynamic synergistic therapy (CPST) holds tremendous promise for treating cancers. Unfortunately, existing CPST applications suffer from complex synthetic procedures, low drug co-loading efficiency, and carrier-related toxicity. To address these issues, we have developed a supramolecular carrier-free self-sensitized nanoassemblies by co-assembling podophyllotoxin (PTOX) and chlorin e6 (Ce6) to enhance CPST efficiency against tumors. The nanoassemblies show stable co-assembly performance in simulative vivo neural environment (∼150 nm), with high co-loading ability for PTOX (72.2 wt%) and Ce6 (27.8 wt%). In vivo, the nanoassemblies demonstrate a remarkable ability to accumulate at tumor sites by leveraging the enhanced permeability and retention (EPR) effect. The disintegration of nanoassemblies following photosensitizer bioactivation triggered by the acidic tumor environment effectively resolves the challenge of aggregation-caused quenching (ACQ) effect. Upon exposure to external light stimulation, the disintegrated nanoassemblies not only illuminate cancer cells synergistically but also exert a more potent antitumor effect when compared with PTOX and Ce6 administered alone. This self-sensitized strategy represents a significant step forward in CPST, offering a unique co-delivery paradigm for clinic cancer treatment.

DNA aptamer-empowered self-assembly full-API nanodrug for enhanced photodynamic and chemotherapy synergistic cancer therapy

Nanomedicine holds promising potential for cancer therapy, yet challenges such as low active pharmaceutical ingredient (API), nanocarrier toxicity, complex preparation processes, and a lack of targeting ability hinder clinical applications. Here, we present a versatile method for preparing DNA aptamer-based full-API nanodrugs (ICS AFANDs). This approach involves the self-assembly of FDA-approved chemotherapeutics (irinotecan), photosensitive drugs (Chlorin e6, Ce6), and the DNA molecule of the Sgc8 aptamer. DNA aptamers are firstly confirmed to not only impart solubilization and targeting ability to ICS AFANDs but also play a pivotal role in engineering and stabilizing the formation of self-assembled nanodrugs. Our method not only significantly enhances the chemotherapy effectiveness of irinotecan by 102-fold, but also improves the near-infrared (NIR) fluorescence properties and photoactivity of Ce6. Combining photodynamic therapy (PDT) and chemotherapy (CT), our ICS AFANDs achieve complete suppression of colorectal cancer growth, with only one dose and one laser treatment, all without apparent side effects. Our strategy is a versatile method for preparing carrier-free and multifunctional DNA nanodrugs for synergistic tumor therapy. The smart and efficient full-API DNA nanodrug not only broadens the scope of synergistic tumor therapy but also facilitates the practical translation of DNA nanodrugs to clinical use.

Tumor Microenvironment‐Activatable Metal‐Phenolic Nanoformulations for Ultrasound‐Boosted Ferroptosis through Triple Regulatory Pathways

AbstractDespite its effectiveness in exterminating tumor cells, ferroptosis is seriously hampered by the high expression of antioxidant glutathione (GSH) and the inadequacy of endogenous H2O2 in tumors. Herein, metal‐phenolic nanoformulations (FNCP NFs) composed of sonosensitizer Chlorin e6 (Ce6), the phenolic GSH consumer naphthazarin, and Fe3+, followed by the modification of PEG2000, are strategically designed and fabricated for ultrasound‐boosted ferroptosis in tumor cells through triple regulatory pathways. The carrier‐free FNCP NFs can rapidly dissociate under tumor microenvironment response with the assistance of ultrasound, releasing Fe2+, Ce6, and naphthazarin. Ce6 and Fe2+ are capable of producing singlet oxygen (1O2) and hydroxyl radicals (·OH) by ultrasound‐activated sonodynamic therapy and Fenton reaction‐mediated chemodynamic therapy (CDT), respectively, which not only induce apoptotic cell death but also lead to the effective accumulation of lipid peroxidation (LPO), resulting in ferroptosis. Meanwhile, the released naphthazarin and the self‐cycling valence alternations of Fe3+/Fe2+ promote the significant decrease of intracellular GSH contents, further inducing the inactivation of glutathione peroxidase 4 (GPX4) and the up‐regulation of LPO levels, eventually realizing the synergistically enhanced ferroptosis. This facile and feasible design for versatile metal‐phenolic nanoformulations offers a new strategy for effectively improving ferroptosis efficiency and multimodal cancer therapies.

Endogenous and exogeneous stimuli-triggered reactive oxygen species evoke long-lived carbon monoxide to fight against lung cancer

Reactive oxygen species (ROS)-associated anticancer approaches usually suffer from two limitations, i.e., insufficient ROS level and short ROS half-life. Nevertheless, no report has synchronously addressed both concerns yet. Herein, a multichannel actions-enabled nanotherapeutic platform using hollow manganese dioxide (H-MnO2) carriers to load chlorin e6 (Ce6) sonosensitizer and CO donor (e.g., Mn2(CO)10) has been constructed to maximumly elevate ROS level and trigger cascade catalysis to produce CO. Therein, intratumoral H2O2 and ultrasound as endogenous and exogeneous triggers stimulate H-MnO2 and Ce6 to produce •OH and 1O2, respectively. The further cascade reaction between ROS and Mn2(CO)10 proceeds to release CO, converting short-lived ROS into long-lived CO. Contributed by them, such a maximumly-elevated ROS accumulation and long-lived CO release successfully suppresses the progression, recurrence and metastasis of lung cancer with a prolonged survival rate. More significantly, proteomic and genomic investigations uncover that the CO-induced activation of AKT signaling pathway, NRF-2 phosphorylation and HMOX-1 overexpression induce mitochondrial dysfunction to boost anti-tumor consequences. Thus, this cascade catalysis strategy can behave as a general means to enrich ROS and trigger CO release against refractory cancers.Graphic

Zinc oxide nanoparticles with catalase-like nanozyme activity and near-infrared light response: A combination of effective photodynamic therapy, autophagy, ferroptosis, and antitumor immunity

We prepared biocompatible and environment-friendly zinc oxide nanoparticles (ZnO NPs) with upconversion properties and catalase-like nanozyme activity. Photodynamic therapy (PDT) application is severely limited by the poor penetration of UV–Visible light and a hypoxic tumor environment. Here, we used ZnO NPs as a carrier for the photosensitizer chlorin e6 (Ce6) to construct zinc oxide–chlorin e6 nanoparticles (ZnO-Ce6 NPs), simultaneously addressing both problems. In terms of penetration, ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6, achieving deep-penetrating photodynamic therapy under long-wavelength light. Interestingly, the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles. As nanozymes, ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors, providing oxygen for photodynamic action and relieving hypoxia. The enhanced photodynamic action produces a large amount of reactive oxygen species, which overactivate autophagy and trigger immunogenic cell death (ICD), leading to antitumor immunotherapy. In addition, even in the absence of light, ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.

Isolation, Identification, and Biological Activities of a New Chlorin e6 Derivative.

Chlorin e6 is a well-known photosensitizer used in photodynamic diagnosis and therapy. A method for identifying and purifying a novel process-related impurity during the synthesis of chlorin e6 has been developed. Its structure was elucidated using NMR and HRMS. This new impurity is formed from chlorophyll b rather than chlorophyll a, which is the source of chlorin e6. The intermediates formed during chlorin e6 synthesis were monitored using HPLC-mass spectrometry. This new impurity was identified as rhodin g7 71-ethyl ester, the structure of which remains unknown to date. The cytotoxic effects of this novel compound in both dark and light conditions were studied against five cancer cell lines (HT29, MIA-PaCa-2, PANC-1, AsPC-1, and B16F10) and a normal cell line (RAW264.7) and compared to those of chlorin e6. Upon irradiation using a laser at 0.5 J/cm2, rhodin g7 71-ethyl ester demonstrated higher cytotoxicity (2-fold) compared to chlorin e6 in the majority of the cancer cell lines. Furthermore, this new compound exhibited higher dark cytotoxicity compared to chlorin e6. Studies on singlet oxygen generation, the accumulation in highly vascular liver tissue, and the production of reactive oxygen species in MIA-PaCa-2 cancer cells via rhodin g7 71-ethyl ester correspond to its higher cytotoxicity as a newly developed photosensitizer. Therefore, rhodin g7 71-ethyl ester could be employed as an alternative or complementary agent to chlorin e6 in the photodynamic therapy for treating cancer cells.

Photodynamic Therapy under Diagnostic Control of Wounds with Antibiotic-Resistant Microflora

Background: Difficulties in the treatment of purulent wounds are caused by bacterial biofilms, which results in decontamination limitations. Infected wounds are not sufficiently susceptible to existing antibiotics, necessitating the search for alternative approaches to reduce the concentration of pathogenic microflora. Methods: This study describes an approach to the effective treatment of wounds by photodynamic inactivation or therapy (PDI/PDT) of antibiotic-resistant microflora under fluorescence control. For this purpose, laser and LED light (660–680 nm) and different groups of photosensitizers (PS) (1% solutions of methylene blue, aluminum phthalocyanine, chlorine e6 and nanocomposites containing these groups of PS) were used. The study included 90 patients with various wounds. Some patients were subjected to fluorescence diagnosis by laser spectral analysis before the PDT. Results: Positive results were achieved in 76 patients (84%, p < 0.05). After the first PDT session, a decrease in the concentration of microflora was noticeable. By the third and seventh days, a significant to complete inactivation of bacteria was obtained. In all patients who were photo-diagnosed before PDT, a significant PS concentration decrease of more than 75% after PDT was obtained. Conclusion: PDT is an effective method for the inactivation of antibiotic-resistant pathogens, including in long non-healing wounds, contributing also to early tissue regeneration.

Multi‐synergistic chemotherapeutic drug assemblies to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics

AbstractThe life‐threatening colorectal cancer exhibits multilevel immunosuppressive characteristics, including low immunogenicity, abnormal cellular metabolism, and acidic immunosuppressive microenvironment. In this work, multi‐synergistic chemotherapeutic drug assemblies are fabricated to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics. Without any drug excipients, the glycolysis inhibitor of lonidamine (LON), indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor of NLG919 (NLG), and the photosensitizer of chlorine e6 could self‐assemble into drug assemblies (LNC) with uniform nano‐size distribution and increased drug stability. Moreover, LNC could also promote cellular uptake and enhance drug penetration to enable efficient drug co‐delivery. Especially, the photodynamic therapy (PDT) of LNC could disrupt tumor cells to release tumor‐associated antigens, thus efficiently suppressing primary tumor growth and improving tumor immunogenicity. Meanwhile, LNC could also reduce the activity of IDO‐1 and attenuate the glycolysis metabolism, thereby reversing the multilevel immunosuppressive characteristics to promote T cell activation. Benefiting from the multi‐synergistic effects, LNC efficiently eradicates the primary tumor growth and also activates systemic antitumor immunity for metastatic tumor inhibition. Such a simple formulation but a multi‐synergistic strategy may accelerate the development of translational nanomedicine for colorectal cancer immunotherapy by using small molecular drug combinations.

Self-assembled copper-based nanoparticles for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma

As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3′-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.Graphical

Cytokine-induced killer cells-mediated chlorin e6-loaded gold nanostars for targeted NIR imaging and immuno-photodynamic combination therapy for lung cancer

Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activity in vivo. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.

Dinuclear Tridentate Ru(II) Complex with Strong Near-Infrared Light-Triggered Anticancer Activity.

The design of the dinuclear Ru(II) complex (Ru2) with strong near-infrared (NIR) absorption properties has been reported for efficient anticancer phototherapy. Under 700 nm LED light excitation, Ru2 exhibited remarkable synergistic type I/II photosensitization ability and photocatalytic activity toward intracellular biomolecules. Ru2 showed impressive 700 nm light-triggered anticancer activity under normoxia and hypoxia compared with the clinically used photosensitizer Chlorin e6. The mechanistic studies showed that Ru2 induced intracellular redox imbalance and perturbed the energy metabolism and biosynthesis in A549 cancer cells. Overall, this work provides a new strategy for developing efficient metal-based complexes for anticancer phototherapy under NIR light.

GSH-responsive prodrug-based nanodrugs for augmenting chemo-photodynamic synergistic therapy against tumors

Malignant tumors are a serious threat to human health, and chemotherapy (CT) is one of the most commonly used strategies in cancer treatment. However, CT often suffers from severe side effects and therapeutic inefficiency, due to poor targeting of antitumor drugs and drug resistance with long-term use. Herein, we developed a GSH-responsive prodrug-based nanodrugs, which was internally encapsulated with the mitomycin C (MMC) prodrug and the photosensitizer Chlorin e6 (Ce6), and with surface-modified aptamers specifically targeting tumors. The nanodrugs not only promoted GSH-responsive CT drug release at the tumor site, but also enhanced the efficacy of Ce6-based photodynamic therapy (PDT) due to the severe redox imbalance in the tumor caused by GSH depletion, thereby improving the chemo- photodynamic synergistic treatment of the tumor. In vivo studies confirmed that the nanodrugs exhibited excellent tumor-targeting capabilities and significant anti-tumor therapeutic effects, offers a promising approach for clinical cancer treatment.

Optical Fiber-Enabled In Situ Photocatalytic Hydrogen Generation for Infiltrating Tumor Therapy in Brain.

In addition to repressing proliferation, inhibiting infiltration of tumor cells is an important strategy to improve the treatments of malignant tumors. Herein, a photocatalyst (pCNMC@Pt) is designed by sequentially assembling manganese dioxide, chlorin e6, and platinum (Pt) nanoparticles onto protonated graphitic carbon nitride. With the help of Z-scheme structure and near-infrared (NIR) photosensitizer, pCNMC@Pt is capable of responding to NIR light to generate large amounts of hydrogen (H2). Taking lactic acid in tumor microenvironment as sacrificial reagent, H2 therapy initiated by the NIR photocatalyst remarkably impedes the growth of glioblastoma (GBM). More importantly, it is found that H2 can suppress the stemness of gliomas stem cells, curbing both proliferation and infiltration of GBM. Furthermore, since pCNMC@Pt and light source is precisely co-localized through a self-built loading and illumination system, GBM in mouse brains can be efficiently treated, providing an alternative gas therapy approach to cure infiltrating tumors. This article is protected by copyright. All rights reserved.

Nanogel-based nitric oxide-driven nanomotor for deep tissue penetration and enhanced tumor therapy

Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.

Sonosynthetic Cyanobacteria Oxygenation for Self-Enhanced Tumor-Specific Treatment.

Photosynthesis, essential for life on earth, sustains diverse processes by providing nutrition in plants and microorganisms. Especially, photosynthesis is increasingly applied in disease treatments, but its efficacy is substantially limited by the well-known low penetration depth of external light. Here, ultrasound-mediated photosynthesis is reported for enhanced sonodynamic tumor therapy using organic sonoafterglow (ultrasound-induced afterglow) nanoparticles combined with cyanobacteria, demonstrating the proof-of-concept sonosynthesis (sonoafterglow-induced photosynthesis) in cancer therapy. Chlorin e6, a typical small-molecule chlorine, is formulated into nanoparticles to stimulate cyanobacteria for sonosynthesis, which serves three roles, i.e., overcoming the tissue-penetration limitations of external light sources, reducing hypoxia, and acting as a sonosensitizer for in vivo tumor suppression. Furthermore, sonosynthetic oxygenation suppresses the expression of hypoxia-inducible factor 1α, leading to reduced stability of downstream SLC7A11 mRNA, which results in glutathione depletion and inactivation of glutathione peroxidase 4, thereby inducing ferroptosis of cancer cells. This study not only broadens the scope of microbial nanomedicine but also offers a distinct direction for sonosynthesis.

Spiderweb-Shaped Iron-Coordinated Polymeric Network as the Novel Coating on Microneedles for Transdermal Drug Delivery Against Infectious Wounds.

Coated microneedles (CMNs) are a minimally invasive platform for immediate-release transdermal drug delivery. However, the practical applications of CMNs have been significantly hindered by the challenges associated with complex formulations, single function, and limited drug loading capacity. This study has developed a spiderweb-shaped iron-coordinated polymeric nanowire network (Fe-IDA NWs). The resulting Fe-IDA NWs are endowed with a certain viscosity due to the synergy of multiple supramolecular interactions. This allows them to replace traditional polymeric thickeners as microneedle coatings. The Fe-IDA NWs-coated microneedles (Fe-IDA MNs) display rapid disintegration in the skin model, which also enables the swift diffusion of Fe-IDA NWs and their payloads into the deeper skin layers. Additionally, Fe-IDA MNs exhibit desirable enzymatic activity and potential antibacterial ability. Thus, Fe-IDA MNs can enhance the therapeutic efficacy against wound infection through synergistic effects, and avoid the overly complicated formulation and the release of nontherapeutic molecules of conventional CMNs. As a proof-of-concept, Fe-IDA MNs loaded with chlorin e6 showed a synergistic chemodynamic-photodynamic antibacterial effect in a methicillin-resistant Staphylococcus aureus-infected wound model in mice. Collectively, this work has significant implications for the future of CMNs-based transdermal drug delivery systems and expands the application fields of metal coordination polymer (MCP) materials.