Gold(III) Porphyrin-Metal-Polyphenolic Nanocomplexes: Breaking Intracellular Redox Environment for Enhancing Mild-Temperature Photothermal Therapy.

Photothermal therapy (PTT) is a promising clinical antitumor strategy. However, local hyperthermia inevitably induces heat damage to adjacent normal tissues, while alternative mild-temperature therapy (MPTT, T < 45 °C) is also inefficient due to the overexpressed hyperthermia-induced heat shock proteins (HSPs) by cancer cells. Therefore, developing PTT strategies with minimizing damage to healthy tissues with improved cellular temperature sensitivity is extremely valuable for clinical application. Herein, we proposed the strategy of disrupting the intracellular redox environment via destroying the ROS-defending systems to promote MPTT. The gold(III) porphyrin-Fe3+-tannic acid nanocomplexes (AuTPP@TA-Fe NPs) were achieved via interfacial cohesion and supramolecular assembly of bioadhesive species, which could trigger the Fenton reaction to produce ·OH radicals and downregulation of reductive TrxR enzyme and mitochondrial chaperone protein Hsp60. The aggravation of oxides and the inactivation of Hsp60 provide favorable pathways for impeding the heat shock-induced self-repair mechanism of cancer cells, which strengthens AuTPP@TA-Fe NPs mediated MPTT.

Photo-triggerable liposomes based on lipid-porphyrin conjugate and cholesterol combination: Formulation and mechanistic study on monolayers and bilayers.

Lipid-porphyrin conjugates are considered nowadays as promising building blocks for the conception of drug delivery systems with multifunctional properties such as photothermal therapy (PTT), photodynamic therapy (PDT), phototriggerable release, photoacoustic and fluorescence imaging. For this aim, we have recently synthesized a new lipid-porphyrin conjugate named PhLSM. This was obtained by coupling pheophorbide-a (Pheo-a), a photosensitizer derived from chlorophyll-a, to egg lyso-sphingomyelin. The pure PhLSMs were able to self-assemble into vesicle-like structures that were however not stable and formed aggregates with undefined structures due to the mismatch between the length of the alkyl chain in sn-1 position and the adjacent porphyrin. Herein, stable PhLSMs lipid bilayers were achieved by mixing PhLSMs with cholesterol which exhibits a complementary packing parameter. The interfacial behavior as well as the fine structures of their equimolar mixture was studied at the air/buffer interface by the mean of Langmuir balance and x-ray reflectomerty (XRR) respectively. Our XRR analysis unraveled the monolayer thickening and the increase in the lateral ordering of PhLSM molecules. Interestingly, we could prepare stable vesicles with this mixture that encapsulate hydrophilic fluorescent probe. The light-triggered release kinetics and the photothermal conversion were studied. Moreover, the obtained vesicles were photo-triggerable and allowed the release of an encapsulated cargo in an ON-OFF fashion.

Targeting drug delivery and efficient lysosomal escape for chemo-photodynamic cancer therapy by a peptide/DNA nanocomplex.

A peptide/DNA nanocomplex was developed for the targeted delivery of chemotherapeutics and photosensitizers to cancer cells for efficient combination therapy. The chemotherapeutic drug doxorubicin (DOX) and the photosensitizer 5,10,15,20-tetra-(1-methylpyridine-4-yl)-porphyrin (TMPyP4) were physically incorporated by an aptamer (AS1411)-modified tetrahedral DNA nanostructure, where the tetrahedral DNA and aptamer-induced G-quadruplex provide binding sites of DOX and TMPyP4. The co-loaded 3A-TDN/DT displayed a targeted uptake by HeLa cancer cells through the high affinity and specificity between AS1411 and nucleolin, a protein overexpressed on many types of cancer cells. A polycationic polymer, mPEG-PAsp(TECH), was synthesized to complex with the DNA nanostructure to efficiently escape from lysosomes via the proton sponge effect upon the enhanced internalization by tumor cells. Under the irradiation of 660 nm laser light, TMPyP4 induced an upregulation of intracellular reactive oxygen species, which combined with DOX to fulfill the efficient inhibition of HeLa cells. Our study demonstrated a biocompatible peptide/DNA composite nanoplatform for combinational cancer therapy via the targeted delivery of therapeutic agents and efficient lysosomal escape.

Light-Activated Biodegradable Covalent Organic Framework-Integrated Heterojunction for Photodynamic, Photothermal, and Gaseous Therapy of Chronic Wound Infection.

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

Metal-Organic Framework-Based Nanoagents for Effective Tumor Therapy by Dual Dynamics-Amplified Oxidative Stress.

Overproduction of reactive oxygen species (ROS) within tumors can cause oxidative stress on tumor cells to induce death, which has motivated us to develop ROS-mediated tumor therapies, such as typical photodynamic therapy (PDT) and Fenton reaction-mediated chemodynamic therapy (CDT). However, these therapeutic modalities suffer from compromised treatment efficacy owing to their limited generation of highly reactive ROS in a tumor microenvironment (TME). In this work, a nanoscale iron-based metal-organic framework, MIL-101(Fe), is synthesized as a Fenton nanocatalyst to perform the catalytic conversion of hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) under the acidic environment and as a biocompatible and biodegradable nanocarrier to deliver a 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer for light-activated singlet oxygen (1O2) generation. By coupling such chemodynamic/photodynamic effects, the photosensitizer-integrated nanoagents (MIL-101(Fe)@TCPP) could enable more ROS production within tumors to induce amplified oxidative damage for tumor-specific synergistic therapy. In vitro results show that MIL-101(Fe)@TCPP nanoagents achieve the acid-responsive CDT and effective PDT, and synergistic CDT/PDT provides an enhanced therapeutic effect. Ultimately, based on such synergistic therapy, MIL-101(Fe)@TCPP nanoagents cause a significant tumor growth inhibition in vivo without severe side effects, showing great potential for anti-tumor application.

Conjugated Coordination Porphyrin-based Nanozymes for Photo-/Sono-Augmented Biocatalytic and Homologous Tumor Treatments.

Porphyrin-based nanozymes (Porzymes) have shown promising application potential to fight against tumors using catalytically generated reactive oxygen species from the excessively produced H2O2 in the tumor microenvironment. However, the low coordination porphyrin (CP) loading ratio, difficult controllable nanostructure, low bioavailability, and low biocatalytic activities of current established Porzymes have severely limited their antitumor applications. Here, a novel malignant melanoma cell membrane-coated Pd-based CP nanoplatform (Trojan Porzymes) has been synthesized for biocatalytic and homologous tumor therapies. The Trojan Porzymes exhibit a high CP loading ratio, uniform nanoscale size, single-atom nanostructure, homologous targeted ability, and high-efficiency photo/sono-augmented biocatalytic activities. The enzyme-like biocatalytic experiments display that the Trojan Porzymes can generate abundant •OH via chemodynamic path and 1O2 via visible light or ultrasound excitation. Then we demonstrate that the Trojan Porzymes show homologous targeting ability to tumor cells and can achieve efficient accumulation and long-term retention in cancer tissues. Our in vivo data further disclose that the photo/sono-assisted chemodynamic therapies can significantly augment the treatment efficiency of malignant melanoma. We believe that our work will afford a new biocatalytic and homologous strategy for future clinical malignant melanoma treatments, which may inspire and guide more future studies to develop individualized biomedicine in precise tumor therapies.

Immune/Hypoxic Tumor Microenvironment Regulation-Enhanced Photodynamic Treatment Realized by pH-Responsive Phase Transition-Targeting Nanobubbles.

Due to a special pathological type of triple-negative breast cancer (TNBC) and the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her 2), targeted therapies are not effective. The lack of effective treatment drugs and insensitivity to the current single-treatment methods are the biggest problems that we face with the TNBC treatment. Therefore, new strategies to achieve selective treatment and further visual efficacy evaluation will be powerful tools against TNBC. Herein, a novel tumor-targeted nanosized ultrasound contrast nanobubble loaded with chlorin e6 (Ce6), metformin (MET), and perfluorohexane (PFH) and covalently connected to the anti-PD-L1 peptide (DPPA-1) in the outer shell was fabricated. When accumulated in acidic tumor tissues, poly(ethylene glycol) (PEG) ligands detach, and DPPA-1 is exposed for programmed death-ligand 1 (PD-L1) targeting and blocking. The released metformin can relieve hypoxia by inhibiting mitochondrial complex I in the tumor microenvironment (TME) and enhance the therapeutic efficacy of Ce6 while synergizing with DPPA-1 by reducing PD-L1 expression. More significantly, photodynamic therapy (PDT) using multifunctional tumor-targeted nanosized ultrasound contrast agents (PD-L1-targeted pH-sensitive chlorin e6 (Ce6) and metformin (MET) drug-loaded phase transitional nanoparticles (Ce6/MET NPs-DPPA-1)) combined with PD-L1 checkpoint blocking can not only reduce tumor-mediated immunosuppression but also produce strong antitumor immunity. This finding provides a new idea for constructing multifunctional TNBC therapeutic nanoagents.

Anisotropic Truncated Octahedral Au with Pt Deposition on Arris for Localized Surface Plasmon Resonance-Enhanced Photothermal and Photodynamic Therapy of Osteosarcoma.

The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.

Self-Assembling Porphyrins as a Single Therapeutic Agent for Synergistic Cancer Therapy: A One Stone Three Birds Strategy.

Combining photodynamic therapy (PDT), chemodynamic therapy (CDT), and ferroptosis is a valuable means for an enhanced anticancer effect. However, traditional combination of PDT/CDT/ferroptosis faces several hurdles, including excess glutathione (GSH) neutralization and preparation complexity. In this work, a versatile multifunctional nanoparticle (HCNP) self-assembled from two porphyrin molecules, chlorin e6 and hemin, is developed. The as-constructed HCNPs exhibit a peroxidase-mimic catalytic activity, which can lead to the in situ generation of endogenous O2, thereby enhancing the efficacy of PDT. Furthermore, the generation of hydroxyl radicals (•OH) in the tumor environment in reaction to the high level of H2O2 and the simultaneous disruption of intracellular GSH endow the HCNPs with the capacity of enhanced CDT, resulting in a more effective therapeutic outcome in combination with PDT. More importantly, GSH depletion further leads to the inactivation of GSH peroxide 4 and induced ferroptosis. Both in vitro and in vivo results showed that the combination of PDT/CDT/ferroptosis realizes highest antitumor efficacy significantly under laser irradiation. Therefore, by integrating the superiorities of O2 and •OH generation capacity, GSH-depletion effect, and bioimaging into a single nanosystem, the HCNPs are a promising single therapeutic agent for tumor PDT/CDT/ferroptosis combination therapy.

Hyaluronic acid-based nanogels derived from multicomponent self-assembly for imaging-guided chemo-photodynamic cancer therapy.

Multifunctional theranostic nanoplatforms integrated of imaging function, multi-modality therapy, stimuli-responsiveness, and targeted delivery are of highly desirable attributes in achieving precise medicine. However, preparation of multifunctional nanoplatforms often involves laborious, multiple steps and inevitably utilizes low-biocompatible or non-functional components. Herein we report a facile, one-step self-assembly strategy to fabricate hyaluronic acid (HA)-based multifunctional tumor theranostic nanoplatform by employing magnetic resonance imaging (MRI) agent Mn2+ as a reversible crosslink agent for histidine-grafted HA, along with simultaneously loading chemotherapeutic agent doxorubicin hydrochloride (DOX) and photodynamic therapy agent chlorin e6, to realize MRI-guided targeted chemo-photodynamic cancer therapy. The targeted delivery and stimuli-responsive payload release were demonstrated in vitro and in vivo. Furthermore, the combined chemo-photodynamic therapy of the nanoassembly dramatically improved the cancer therapeutic outcome, in comparison with that of free DOX and nanoplatform solely loaded DOX in a melanoma bearing mice. Our one step assemble strategy is of great potential in clinic transformation.

Two-Dimensional Metal-Organic Framework Film for Realizing Optoelectronic Synaptic Plasticity.

2D metal-organic framework (MOF) film as the active layer show promising application prospects in various fields including sensors, catalysis, and electronic devices. However, exploring the application of 2D MOF film in the field of artificial synapses has not been implemented yet. In this work, we fabricated a novel 2D MOF film (Cu-THPP, THPP=5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine), and further used it as an active layer to explore the application in the simulation of human brain synapses. It shows excellent light-stimulated synaptic plasticity properties, and exhibits the foundation function of synapses such as long-term plasticity (LTP), short-term plasticity (STP), and the conversion of STP to LTP. Most critically, the MOF based artificial synaptic device exhibits an excellent stability in atmosphere. This work opens the door for the application of 2D MOF film in the simulation of human brain synapses.

Multifunctional Programmable DNA Nanotrain for Activatable Hypoxia Imaging and Mitochondrion-Targeted Enhanced Photodynamic Therapy.

Programmable DNA-based nanostructures (e.g., nanotrains, nanoflowers, and DNA dendrimers) provide new approaches for safe and effective biological imaging and tumor therapy. However, few studies have reported that DNA-based nanostructures respond to the hypoxic microenvironment for activatable imaging and organelle-targeted tumor therapy. Herein, we innovatively report an azoreductase-responsive, mitochondrion-targeted multifunctional programmable DNA nanotrain for activatable hypoxia imaging and enhanced efficacy of photodynamic therapy (PDT). Cyanine structural dye (Cy3) and black hole quencher 2 (BHQ2), which were employed as a fluorescent mitochondrion-targeted molecule and azoreductase-responsive element, respectively, covalently attached to the DNA hairpin monomers. The extended guanine (G)-rich sequence at the end of the DNA hairpin monomer served as a nanocarrier for the photosensitizer 5,10,15,20-tetrakis(4-N-methylpyridiniumyl) porphyrin (TMPyP4). Upon initiation between the DNA hairpin monomer and initiation probe, the fluorescence of Cy3 and the singlet oxygen (1O2) generation of TMPyP4 in the programmable nanotrain were effectively quenched by BHQ2 through the fluorescence resonance energy transfer (FRET) process. Once the programmable nanotrain entered cancer cells, the azo bond in BHQ2 will be reduced to amino groups by the high expression of azoreductase under hypoxia conditions; then, the fluorescence of Cy3 and the 1O2 generation of TMPyP4 will significantly be restored. Furthermore, due to the mitochondrion-targeting characteristic endowed by Cy3, the TMPyP4-loaded nanotrain would accumulate in the mitochondria of cancer cells and then demonstrate enhanced PDT efficacy under light irradiation. We expect that this programmable DNA nanotrain-based multifunctional nanoplatform could be effectively used for activatable imaging and high performance of PDT in hypoxia-related biomedical field.

Chlorin e6-1,3-diphenylisobenzofuran polymer hybrid nanoparticles for singlet oxygen-detection photodynamic abaltion.

A dual-functional nanosysterm is developed by means of Chlorin e6 (Ce6) as photosensitizer and 1,3-Diphenylisobenzofuran (DPBF) as fluorescent singlet oxygen (1O2) probe. Under 660 nm laser irradiation, Ce6 exhibites efficient 1O2 generation, and subsequently the production of 1O2 is assessed by the ratiometric fluorescence of PFO and DPBF under one-photon and two-photon excitation mode. The nanoparticles with excellent biocompatibility can be internalized into Hela cells and applied for tumor treatment. For intracellular PDT, the nanoparticles perform a high phototoxicity, while the PDT proccess can be evaluated in time by monitoring fluorescence signals of DPBF. This theranostic nanosysterm provides a facile strategy to fabricate 1O2-detection PDT, which can realize accurate and efficient photodynamic therapy based on singlet oxygen detection.

Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line.

Melanoma is the most dangerous form of skin cancer, with an abrupt growth of its incidence over the last years. It is extremely resistant to traditional treatments such as chemotherapy and radiotherapy, but therapies for this cancer are gaining attention. Photodynamic therapy (PDT) is considered an effective modality to treat several types of skin cancers and can offer the possibility to treat one of the most aggressive ones: melanoma. In this work, the effect of PDT on a melanotic cell line (B16F10 cells) was assessed by exposing cultured cells to 5,10,15-tris(pentafluorophenyl)-20-(4-pyridyl)porphyrin (PS1) and to its chlorin (PS2) and isobacteriochlorin (PS3) corresponding derivatives and red LED light (λ = 660 ± 20 nm). The PDT effect in the cells' viability was measured using the MTT assay. The cell apoptosis was quantified by flow cytometry, and the subcellular localization of the photosensitizer was determined by fluorescence microscopy. In addition, the ability of PS2 to generate superoxide radicals was qualitatively assessed by tyrosine nitration. The results show that the efficiency of the PDT process is dependent on the structure of the PS and on their ability to produce singlet oxygen. Besides that, the photoactivation efficiency is highly dependent on the cellular sublocalization of the PS and on its cellular uptake and singlet oxygen production. We also found that the resistant cell line B16F10 has distinctive chlorin, isobacteriochlorin, or porphyrin-specific resistance profiles. Furthermore, it is shown that the highly fluorescent chlorin derivative PS2 can also be considered in imaging diagnostics.

Engineering a photosensitizer nanoplatform for amplified photodynamic immunotherapy via tumor microenvironment modulation.

Photosensitizer-based photodynamic therapy (PDT) can not only kill tumor cells by the generated cytotoxic reactive oxygen species (ROS), but also trigger immunogenic cell death (ICD) and activate an immune response for immunotherapy. However, such photodynamic immunotherapy suffers from major obstacles in the tumor microenvironment. The hypoxic microenvironment greatly weakens PDT, while the immunosuppressive tumor microenvironment caused by aberrant tumor blood vessels and indoleamine 2,3-dioxygenase (IDO) leads to a significant reduction in immunotherapy. To overcome these obstacles, herein, an engineered photosensitizer nanoplatform is designed for amplified photodynamic immunotherapy by integrating chlorin e6 (Ce6, a photosensitizer), axitinib (AXT, a tyrosine kinase inhibitor) and dextro-1-methyl tryptophan (1MT, an IDO inhibitor). In our nanoplatform, AXT improves the tumor microenvironment by normalizing tumor blood vessels, which not only promotes PDT by reducing the level of hypoxia of the tumor microenvironment, but also promotes immunotherapy through facilitating infiltration of immune effector cells into the tumor and reversing the immunosuppressive effect of vascular endothelial growth factor (VEGF). Moreover, 1MT effectively inhibits the activity of IDO, further reducing the immunosuppressive nature of the tumor microenvironment. Therefore, this nanoplatform demonstrates an amplified photodynamic immunotherapy via tumor microenvironment modulation, exhibiting outstanding therapeutic efficacy against tumor growth and metastasis with negligible side toxicity. The current concept of engineering photosensitizer nanoplatforms for overcoming photodynamic immunotherapy obstacles provides a promising strategy against tumors.

Photoinduced charge transfer in Zn(II) and Au(III)-ligated symmetric and asymmetric bacteriochlorin dyads: A computational study.

The excited-state properties and photoinduced charge-transfer (CT) kinetics in a series of symmetrical and asymmetrical Zn- and Au-ligated meso-meso-connected bacteriochlorin (BChl) complexes are studied computationally. BChl derivatives, which are excellent near-IR absorbing chromophores, are found to play a central role in bacterial photosynthetic reaction centers but are rarely used in artificial solar energy harvesting systems. The optical properties of chemically linked BChl complexes can be tuned by varying the linking group and involving different ligated metal ions. We investigate charge transfer in BChl dyads that are either directly linked or through a phenylene ring (1,4-phenylene) and which are ligating Zn or Au ions. The directly linked dyads with a nearly perpendicular arrangement of the BChl units bear markedly different properties than phenylene linked dyads. In addition, we find that the dielectric dependence of the intramolecular CT rate is very strong in neutral Zn-ligated dyads, whereas cationic Au-ligated dyads show negligible dielectric dependence of the CT rate. Rate constants of the photo induced CT process are calculated at the semiclassical Marcus level and are compared to fully quantum mechanical Fermi's golden rule based values. The rates are calculated using a screened range separated hybrid functional that offers a consistent framework for addressing environment polarization. We study solvated systems in two solvents of a low and a high scalar dielectric constant.

Hydroxy-corrole and its gallium(III) complex as new photosensitizer for photodynamic therapy against breast carcinoma.

Three mono-hydroxy corroles 1-3 and their gallium(III) complexes Ga1-3 were synthesized, and their photodynamic antitumour activities towards breast cancer cells were investigated. All corroles showed excellent cytotoxicity against the MDA-MB-231 and 4T1 cell lines upon light irradiation at 625 nm. Ga3 exhibited excellent phototoxicity and selectivity against MDA-MB-231 cells, with an IC50 of 0.06 ± 0.03 µM and a selective index value of 1338.83 (relative to human normal Huvec cells). The performance of Ga3 was even better than that of the clinical photodynamic therapy drug m-THPC. A preliminary mechanistic investigation revealed that corrole 3 and Ga3 were mainly located in the cytoplasm. Upon irradiation, they could generate intracellular reactive oxygen to destroy the mitochondrial membrane potential and arrest the cell cycle at the sub-G1 phase. Flow cytometry revealed that corrole 3 and Ga3 induced cancer cell apoptosis after photodynamic treatment. Corrole 3 and Ga3 displayed negligible cytotoxicity in the dark. These results suggest that corrole 3 and Ga3 are promising candidates for use in the photodynamic therapy of breast cancer.

A Janus upconverting nanoplatform with biodegradability for glutathione depletion, near-infrared light induced photodynamic therapy and accelerated excretion.

The major limitations of photodynamic therapy (PDT) are the poor tissue penetration of excitation light and the neutralization of reactive oxygen species (ROS) generated by overexpressed glutathione (GSH) in cancer cells. Despite tremendous efforts to design nanoplatforms, PDT still suffers from unsatisfactory effects. Furthermore, the residual of nanomaterials in the body has restricted their clinical application. To address these issues, Janus nanocomposites containing an Yb/Er codoped NaYF4 upconverting nanocrystal head and a disulfide-bridged mesoporous organosilicon body (UCN/MON) with loaded chlorin e6 (Ce6) were designed. On one hand, the upconverting nanocrystal head can convert near-infrared (NIR) light into visible light to activate Ce6 to release ROS. On the other hand, the silica body can be degraded though a redox reaction with GSH, to not only improve the tumor selectivity of the photosensitizer by redox- and pH-triggered Ce6 release, but also diminish the concentration of GSH in cancer cells to reduce the depletion of ROS. Thereby, an enhanced PDT triggered by NIR irradiation was achieved. Furthermore, UCN/MONs showed a higher clearance rate after therapeutic actions than nonbiodegradable UCN/MSNs due to their biocompatibility. Taken together, this work revealed the potential of UCN/MONs for highly efficient and NIR-induced PDT, highlighting the prospects of UCN/MONs in the clinic.

A tumor-microenvironment fully responsive nano-platform for MRI-guided photodynamic and photothermal synergistic therapy.

Multifunctional intelligent theranostics agents are promising for next-generation oncotherapy. We fabricated a tumor-microenvironment (TME)-responsive carbon nanotube (CNT)-based nanoplatform for T1 weighted magnetic resonance imaging (MRI)-guided synergistic photodynamic and photothermal therapy (PDT and PTT). CNTs convert near infrared (NIR) radiation into hyperthermia for PTT, and can effectively deliver their cargo into cells due to their unique 1D nanostructure. The CNT@MnO2-PEG@Ce6 nanomedicine was internalized into tumor cells, and rapidly released the photosensitizer (Ce6) in response to the low pH and high glutathione (GSH) levels characteristic of the TME. The degradation of the MnO2 layer under the same conditions released Mn2+ for T1-MRI. Furthermore, catalytic decomposition of the excess H2O2 into oxygen by MnO2 enhanced the efficacy of PDT, relieved hypoxia, and increased consumption of superfluous GSH to mitigate the effects of excessive reactive oxygen species (ROS) generation during PDT. MRI-guided PDT and PTT synergistically inhibited tumor cell growth in vitro, and ablated tumors in vivo. The side effects were negligible due to specific tumor cell targeting via surface modification with folic-PEG, and enhanced permeability and retention. Taken together, CNT@MnO2-PEG is a fully TME-responsive theranostics nanoplatform for targeted tumor ablation and real-time disease tracking.

Metal-Organic Frameworks with Enhanced Photodynamic Therapy: Synthesis, Erythrocyte Membrane Camouflage, and Aptamer-Targeted Aggregation.

Here, ferric oxide-loaded metal-organic framework (FeTCPP/Fe2O3 MOF) nanorice was designed and constructed by the liquid diffusion method. The introduction of iron metal nodes and the loading of Fe2O3 can effectively catalyze the Fenton reaction to produce hydroxyl radicals (•OH) and overcome the hypoxic environment of tumor tissue by generating oxygen. The monodispersity and porosity of the porphyrin photosensitizers in the MOF structure exposed more active sites, which promoted energy exchange between porphyrin molecules and oxygen molecules for photodynamic therapy (PDT) treatment. Therefore, the generated hydroxyl radicals and singlet oxygen (1O2) can synergistically act on tumor cells to achieve the purpose of improving tumor therapy. Then the erythrocyte membrane was camouflaged to enhance blood circulation and tissue residence time in the body, and finally, the targeted molecule AS1411 aptamer was modified to achieve the high enrichment of MOF photosensitizers on a tumor domain. As a result, the MOF nanorice camouflaged by the erythrocyte membrane can effectively reduce side effects and improve the therapeutic effect of PDT and chemo-dynamic therapy (CDT). The study not only improved the efficacy of PDT and CDT in essence from the MOF nanorice but also used the camouflage method to further concentrate FeTCPP/Fe2O3 on the tumor sites, achieving the goal of multiple gains. These results will provide theoretical and practical directions for the development of tumor-targeted MOF nanomaterials.