Photodynamic Therapeutic Effect Research Articles

Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles.

Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.

Solvent-mediated synthesis of 2D In-TCPP MOF nanosheets for enhanced photodynamic antibacterial therapy

Two-dimensional (2D) metal-organic frameworks (MOFs) have emerged as promising photosensitizers in photodynamic therapy in recent years. In comparison to bulk MOFs, constructing 2D MOFs can increase the presence of active sites through increasing the surface area ratio. Herein, we report a simple solvent-mediated synthesis method for preparation of 2D porphyrin-based MOF (In-TCPP) nanosheets without the addition of any surfactants as an efficient photosensitizer for enhancing photodynamic antibacterial therapy. The accurate regulation of the morphology and size of 2D In-TCPP nanosheets can be achieved by varying the ratio of water to N,N-dimethylformamide solvent with the appropriate assistance of pyridine. The optimal synthesized 2D In-TCPP nanosheets exhibit a diameter of 70-120 nm and a thickness of 21.5-27.4 nm. Promisingly, 2D In-TCPP nanosheets produce a higher amount of 1O2 when exposed to 660 nm laser compared to the In-TCPP bulk, indicating that the smaller nanosheets possess more active sites for reactive oxygen species generation and can greatly improve the antibacterial photodynamic therapeutic effect. Both the in vitro and in vivo results prove that the In-TCPP nanosheets can be used as a photosensitizer for efficient photodynamic antibacterial therapy to kill S. aureus and promote wound healing.

Endoplasmic reticulum-targeted iridium(III) photosensitizer induces pyroptosis for augmented tumor immunotherapy

An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy.

Targeted photodynamic therapy technique of Janus nanoparticles on breast cancer

Spherical gold/polyacrylic acid (Au/PAA) polymer–inorganic Janus nanoparticles (JNPs) with simultaneous therapeutic and targeting functions were fabricated. The obtained Au/PAA JNPs were further selectively functionalized with folic acid (FA) and thiol PEG amine (SH-PEG-NH2) on Au sides to provide superior biocompatibility and active targeting, while the other PAA sides were loaded with 5-aminolevulinic acid (5-ALA) to serve as a photosensitizer (PS) for photodynamic therapeutic (PDT) effects on MCF-7 cancer cells. The PS loading of 5-ALA was found to be 83% with an average hydrodynamic size and z-potential of 146 ± 0.8 nm and −6.40 mV respectively for FA-Au/PAA-ALA JNPs. The in vitro PDT study of the JNPs on MCF-7 breast cancer cells under 636 nm laser irradiation indicated the cell viability of 24.7% ± 0.5 for FA-Au/PAA-ALA JNPs at the IC50 value of 0.125 mM. In this regard, the actively targeted FA-Au/PAA-ALA JNPs treatment holds great potential for tumour therapy with high cancer cell-killing efficacy.

Biotin-new indocyanine green conjugate: Synthesis, invitro photocytotoxicity and invivo biodistribution.

New indocyanine green (ICG) (IR820) is one of the ICG derivatives and attracts increasing attention for cancer management. However, the unsatisfactory tumor targeting ability of IR820 significantly limits its applications for cancer theranostics. Biotin receptor is overexpressed on the membrane of various tumor cells and biotin modified nanocarriers have been reported to enhance the tumor targeting ability on several tumor types. In this work, biotin-new ICG conjugate (Biotin-SS-IR820) was prepared for tumor-targeted IR820 delivery. Biotin and IR820 were coupled through cystamine. The synthesized Biotin-SS-IR820 was characterized by 1 H NMR, FT-IR and HRMS. The invitro singlet oxygen generation study shows that Biotin-SS-IR820 exhibits similar singlet oxygen generation as compared to IR820 upon 660 nm laser irradiation (0.8 W/cm2 ). The cellular uptake study shows that Biotin-SS-IR820 shows enhanced cellular uptake amount as compared to IR820 on 4T1 cells. As a result, Biotin-SS-IR820 displays enhanced invitro photodynamic therapeutic effect against 4T1 cells as compared to IR820. In invivo biodistribution study, Biotin-SS-IR820 shows enhanced tumor accumulation as compared to IR820. Biotin-SS-IR820 developed in this work shows promising prospects for targeted delivery of IR820 to biotin receptor overexpressed tumors.

Uridine-Modified Ruthenium(II) Complex as Lysosomal LIMP-2 Targeting Photodynamic Therapy Photosensitizer for the Treatment of Triple-Negative Breast Cancer.

Lysosome-targeted photodynamic therapy, which enhances reactive oxygen species (ROS)-responsive tumor cell death, has emerged as a promising strategy for cancer treatment. Herein, a uridine (dU)-modified Ru(II) complex (RdU) was synthesized by click chemistry. It was found that RdU exhibits impressive photo-induced inhibition against the growth of triple-negative breast cancer (TNBC) cells in normoxic and hypoxic microenvironments through ROS production. It was further revealed that RdU induces ferroptosis of MDA-MB-231 cells under light irradiation (650 nm, 300 mW/cm2). Additional experiments showed that RdU binds to lysosomal integral membrane protein 2 (LIMP-2), which was confirmed by the fact that RdU selectively localizes in the lysosomes of MDA-MB-231 cells and significantly augments the levels of LIMP-2. Molecular docking simulations and an isothermal titration calorimetry assay also showed that RdU has a high affinity to LIMP-2. Finally, in vivo studies in tumor-bearing (MDA-MB-231 cells) nude mice showed that RdU exerts promising photodynamic therapeutic effects on TNBC tumors. In summary, the uridine-modified Ru(II) complex has been developed as a potential LIMP-2 targeting agent for TNBC treatment through enhancing ROS production and promoting ferroptosis.

Hypoxia and Singlet Oxygen Dual-Responsive Micelles for Photodynamic and Chemotherapy Therapy Featured with Enhanced Cellular Uptake and Triggered Cargo Delivery.

Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer. The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model. The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model. The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.

Photodynamic Therapeutic Effect during 5-Aminolevulinic Acid-Mediated Photodynamic Diagnosis-Assisted Transurethral Resection of Bladder Tumors.

Photodynamic diagnosis-assisted transurethral resection of bladder tumors (PDD-TURBT) enhances detection of elusive lesions compared to standard white light-transurethral resection of bladder tumors (WL-TURBT). If minimal light exposure during PDD-TURBT induces the accumulation of reactive oxygen species (ROS), potentially resulting in phototoxicity in small lesions, apoptosis may be triggered in residual small tumors, allowing them to escape resection. We investigated the hypothesis of a potential photodynamic therapeutic effect during PDD-TURBT. Our study, conducted between January 2016 and December 2020 at Nara Medical University Hospital, focused on a specific emphasis on ROS production. Immunohistochemical analysis for thymidine glycol and N ε -hexanoyl-lysine was performed on 69 patients who underwent 5-aminolevulinic acid-mediated PDD-TURBT and 28 patients who underwent WL-TURBT. Additionally, we incrementally applied the minimal irradiation energy to T24 and UM-UC-3 cells treated with 5-aminolevulinic acid using instruments similar to those used in PDD-TURBT and evaluated intracellular ROS production and phototoxicity. Immunohistochemical analysis revealed a significant increase in production of thymidine glycol and N ε -hexanoyl-lysine within the PDD-TURBT group. In T24 and UM-UC-3 cells treated with 5-aminolevulinic acid and light exposure, immunofluorescent staining demonstrated a dose-dependent increase in intracellular ROS production. In addition, higher irradiation energy levels were associated with a greater increase in ROS production and phototoxicity, as well as more significant decrease in mitochondrial membrane potential. Although the irradiation energy used in PDD-TURBT did not reach the levels commonly used in photodynamic therapy, our findings support the presence of a potential cytotoxic effect on bladder lesions during PDD-TURBT.

Ferroptosis-inducing photosensitizers alleviate hypoxia tumor microenvironment for enhanced fluorescence imaging-guided photodynamic therapy.

This study describes H2O2-activated photosensitizer nanoparticles (ICyHD NPs), which inhibit histone deacetylase via binding Zn2+ to induce ferroptosis and upregulate the intracellular O2, thus resulting in enhanced photodynamic therapeutic effect. ICyHD NPs exert strong antitumor effects on mice and have improved the therapeutic precision via observing the increase in cellular fluorescence.

Self‐Promoted Targeting Delivery of Nanodrug Through Chemotherapeutic Upregulation of CD47 for Triple Negative Breast Cancer Therapy

AbstractThe high heterogeneity of receptor expression and varied chemotherapeutic sensitivity seriously compromise the therapeutic outcome of triple‐negative breast cancer (TNBC)‐targeting nanodrugs. In this work, a TNBC‐targeting nanodrug (designated as CPU) equipped with self‐promoted targeting property through chemotherapeutic upregulation of CD47 is constructed, enabling synergistic chemo/photodynamic therapy. Specifically, the hydrophobic docetaxel (DOC), which can upregulate the expression of CD47 in TNBC cells, is loaded in the nanomicelles (designated as P‐Pep) assembled from a protoporphyrin IX (PPIX)‐labeled amphiphilic chimeric peptide of Fmoc‐K(PPIX)‐AWSATWSNYWRH, obtaining the ca. 196 nm CPU. Aided by the enhanced permeability and retention effect and guidance of CD47‐binding peptide sequence, CPU is verified to prefer to accumulate in CD47 overexpressed TNBC cells, which can recruit more CPU by upregulating CD47 expression post‐treatment of DOC. Both in vitro and in vivo results demonstrate the superior tumor targeting ability, which can extensively amplify chemotherapeutic and photodynamic therapeutic effects while evading obvious adverse effects. The self‐promoted targeting strategy will inspire the design of nanodrugs for the personalized therapy of tumors with high heterogeneity and resistance.

Exudate-Induced Gelatinizable Nanofiber Membrane with High Exudate Absorption and Super Bactericidal Capacity for Bacteria-Infected Wound Management.

Invasion of bacteria and continuous oozing of exudate are significant causes of interference with the healing of infected wounds. Therefore, an exudate-induced gelatinizable and near-infrared (NIR)-responsive nanofiber membrane composed of polyvinyl alcohol (PVA), carboxymethyl chitosan (CMC), and Fe-doped phosphomolybdic acid (Fe-PMA) with exceptional exudate absorption capacity and potent bactericidal efficacy is developed and denoted as the PVA-FP-CMC membrane. After absorbing exudate, the fiber membrane can transform into a hydrogel membrane, forming coordination bonds between the Fe-PMA and CMC. The unique exudate-induced gelation process imparts the membrane with high exudate absorption and retention capability, and the formed hydrogel also traps the bacteria that thrive in the exudate. Moreover, it is discovered for the first time that the Fe-PMA exhibits an enhanced photothermal conversion capability and photocatalytic activity compared to the PMA. Therefore, the presence of Fe-PMA provides the membrane with a photothermal and photodynamic therapeutic effect for killing bacteria. The PVA-FP-CMC membrane is proven with a liquid absorption ratio of 520.7%, a light-heat conversion efficiency of 41.9%, high-level generation of hydroxyl radical (•OH) and singlet oxygen (1O2), and a bacterial killing ratio of 100% for S. aureus and 99.6% for E. coli. The treatment of infected wounds on the backs of rats further confirms the promotion of wound healing by the PVA-FP-CMC membrane with NIR irradiation. Overall, this novel functional dressing for the synergistic management of bacteria-infected wounds presents a promising therapeutic strategy for tissue repair and regeneration.

Insights into eutectic formation and photodynamic therapeutic effects produced by folic acid on wound healing by an allantoin-fructose system

An insight has been provided into the eutectic formation and cutaneous wound healing potential of a binary allantoin/β-D-fructose system (AF). The system was blended with folic acid for light-aided wound therapy. Solid–liquid binary phase diagram showed a differential melting depression of 88°C from the ideal line and the existence of eutectic at X1 = X2 = 0.5. Simulations of molecular mechanics showed the involvement of hydantoin C=O and ureido –NH in hydrogen bonding with hydroxyl or hydroxymethyl groups of fructose. In the eutectic-folic acid blend (AFF), H-bonds were present between =N of pterin ring A and hydantoin –NH. Additionally, pi-sigma interactions involving pterin rings and pyranose moiety were revealed. The bulk density variations showed the disruption of the allantoin template after eutectic formation. An in-depth attenuated total reflectance infrared spectroscopic analysis endorsed the findings of other investigations and vibrational frequencies of interacting functionalities were shifted to different extents. The thermal stability of the eutectic mixture was markedly compromised after the addition of folic acid. Differential scanning calorimetry indicated the presence of co-crystal in addition to eutectic. Eutectic and its blend produced nearly the same healing effects in non-infected cutaneous wounds in rabbit models under normal and photodynamic wound therapy.

An AIE Metal Iridium Complex: Photophysical Properties and Singlet Oxygen Generation Capacity

Photodynamic therapy (PDT) has garnered significant attention in the fields of cancer treatment and drug-resistant bacteria eradication due to its non-invasive nature and spatiotemporal controllability. Iridium complexes have captivated researchers owing to their tunable structure, exceptional optical properties, and substantial Stokes displacement. However, most of these complexes suffer from aggregation-induced quenching, leading to diminished luminous efficiency. In contrast to conventional photosensitizers, photosensitizers exhibiting aggregation-induced luminescence (AIE) properties retain the ability to generate a large number of reactive oxygen species when aggregated. To overcome these limitations, we designed and synthesized a novel iridium complex named Ir-TPA in this study. It incorporates quinoline triphenylamine cyclomethylated ligands that confer AIE characteristics for Ir-TPA. We systematically investigated the photophysical properties, AIE behavior, spectral features, and reactive oxygen generation capacity of Ir-TPA. The results demonstrate that Ir-TPA exhibits excellent optical properties with pronounced AIE phenomenon and robust capability for producing singlet oxygen species. This work not only introduces a new class of metal iridium complex photosensitizer with AIE attributes but also holds promise for achieving remarkable photodynamic therapeutic effects in future cellular experiments and biological studies.

The applications of carbon dots in oral health: A scoping review.

This scoping review aims to provide an overview of the research and potential applications of carbon dots (CDs) for oral health purposes. Systematic literature searches were performed on PubMed and Web of Science databases (up to February 2023). Two co-authors selected the published works independently and extracted the data in accordance with the PRISMA statement. Studies with the application of CDs for oral health purposes were included. Among 152 articles, 19 articles were finally selected. Eight studies investigated the anti-microbial effects of CDs against, for example, oral pathogens, eight studies explored the applicability of CDs in relation to oral cancer, and three studies investigated CDs in relation to cell differentiation and tissue regeneration in oral health. The studies showed the promising potential of CDs in oral health, particularly for inducing bacterial killing by increasing reactive oxygen species, killing oral cancer cells via photodynamic therapeutic effects, and inducing dental pulp and periodontal bone regeneration. The findings show that CDs have the potential to be utilized in the future for various oral health purposes. Besides, these results underline the broad-spectrum applicability of CDs, crossing the borders of oral health.

ROS-responsive self-activatable photosensitizing agent for photodynamic-immunotherapy of cancer.

Photodynamic therapy (PDT), as a non-invasive and spatiotemporally controllable modality, exhibits great potential in cancer treatment. However, the efficiency of reactive oxygen species (ROS) production was restricted to the hydrophobic characteristics and aggregation-caused quenching (ACQ) of photosensitizers. Herein, we designed a ROS self-activatable nano system (denoted as PTKPa) based on poly(thioketal) conjugated with photosensitizers (PSs) pheophorbide A (Ppa) on the polymer side chains for suppressing ACQ and enhancing PDT. The process of self-activation is that ROS, which is derived from laser irradiated PTKPa, as an activating agent accelerates poly(thioketal) cleavage with the release of Ppa from PTKPa. This in turn generates abundant ROS, accelerates degradation of the remaining PTKPa and amplifies the efficacy of PDT with more tremendous ROS generated. Moreover, these abundant ROS can amplify PDT-induced oxidative stress, cause irreversible damage to tumor cells and achieve immunogenic cell death (ICD), thereby boosting the efficacy of photodynamic-immunotherapy. These findings provide new insights into ROS self-activatable strategy for enhancing cancer photodynamic- immunotherapy. STATEMENT OF SIGNIFICANCE: This work described an approach to utilize ROS-responsive self-activatable poly(thioketal) conjugated with pheophorbide A (Ppa) for suppressing aggregation-caused quenching (ACQ) and enhancing photodynamic-immunotherapy. The ROS, generated from the conjugated Ppa upon 660nm laser irradiation, as a triggering agent which initiates the release of Ppa with poly(thioketal) degradation. That in turn generates abundant ROS and facilitates degradation of the remaining PTKPa, resulting in oxidative stress to tumor cells and achieving immunogenic cell death (ICD). This work provides a promising solution to improve tumor photodynamic therapeutic effects.

Facile synthesis of metformin loaded Mn3O4-HAp magnetic hydroxyapatite nanocomposites for T1-magnetic resonance imaging guided targeted chemo-phototherapy in vitro

Magnetic hydroxyapatite nanocomposites are promising candidates for various biomedical applications. However, the uncontrolled growth with the unfavorable size limits their widespread utilization in real-time applications. Herein, a facile method was utilized to fabricate uniform spherical-shaped nanocomposites of manganese oxide combined hydroxyapatite (Mn3O4-HAp) with an average size of about 28 nm. The structural characterization reveals the presence of Mn3O4 in the crystalline phase, confined by HAp to give a composite structure. The biocompatibility and drug loading capability of Mn3O4-HAp nanocomposites are improved by surface modification using Food and Drug Administration-approved triblock copolymer Pluronic® F-127, followed by folic acid (FA) for targeting ability. Taking advantage of the surface properties of the polymer and the drug delivery potential of HAp, metformin was encapsulated in the prepared nanocomposites with a loading capacity of 98 %. The prepared nanocomposites indicate promising cell viability up to 87 % and an excellent drug release profile in an acidic atmosphere. Moreover, the magnetic component Mn3O4 presents auspicious T1-Magnetic resonance imaging with notable r1 relaxivity of 2.166 mM−1s−1. Further, the Mn3O4-HAp@PF127-FA-drug nanocomposites demonstrate good cellular uptake and excellent reactive oxygen species (ROS) production under low-intensity UV irradiation, resulting in a remarkable photodynamic therapeutic effect. The results showed that the designed Mn3O4-HAp nanocomposites are promising targeted chemo-theranostic agents.

Development of Sulfonamide‐Functionalized Charge‐Reversal AIE Photosensitizers for Precise Photodynamic Therapy in the Acidic Tumor Microenvironment

AbstractTumor‐targeted photodynamic therapy (PDT) is desirable as it can achieve efficient killing of tumor cells with no or less harm to normal cells. Herein, a facile molecular engineering strategy is developed for photosensitizers (PSs) with aggregation induced emission (AIE) characteristics and responsive properties to the acidic tumor microenvironment (TME). By the marriage of pH‐sensitive sulfonamide moieties with AIE PSs, two near‐infrared AIE luminogens called DBP‐SPy and DBP‐SPh are designed and synthesized. Both luminogens can form negatively charged nanoaggregates in the aqueous medium at physiological pH. The DBP‐SPy nanoaggregates undergo surface charge conversion to become positive at pH close to the signature pH of TME, while DBP‐SPh nanoaggregates show no such property. The endowed response to acidic TME enables the enhanced cellular uptake of DBP‐SPy at pH = 6.8. By contrast, its cellular uptake is much sacrificed at pH 7.4. As a result, under white light irradiation, DBP‐SPy nanoaggregates demonstrate a considerable photodynamic therapeutic effect on cancer cells in vitro and excellent tumor growth inhibition in vivo. Hence, this study not only provides an acidic TME‐responsive AIE PS for precise PDT, but also inspires new design strategies for AIE‐based theragnostic systems with targeting characteristics.

Integration of TADF Photosensitizer as "Electron Pump" and BSA as "Electron Reservoir" for Boosting Type I Photodynamic Therapy.

Type I photosensitization provides an effective solution to the problem of unsatisfactory photodynamic therapeutic (PDT) effects caused by the tumor hypoxia. The challenge in the development of Type I mode is to boost the photosensitizer's own electron transfer capacity. Herein, we found that the use of bovine serum albumin (BSA) to encapsulate a thermally activated delayed fluorescence (TADF) photosensitizer PS can significantly promote the Type I PDT process to generate a mass of superoxide anions (O2•-). This Type I photosensitization opened a new strategy by employing BSA as "electron reservoir" and TADF photosensitizer as "electron pump". We integrated these roles of BSA and PS in one system by preparing nanophotosensitizer PS@BSA. The Type I PDT performance was demonstrated with tumor cells under hypoxic conditions. Furthermore, PS@BSA took full advantage of the tumor-targeting role of BSA and achieved efficient PDT for tumor-bearing mice in the in vivo experiments. This work provides an effective route to improve the PDT efficiency of hypoxic tumors.

Ratiometric singlet oxygen self-detecting and oxygen self-supplying nanosensor for real-time photodynamic therapy feedback and therapeutic effect enhancement

Integration of singlet oxygen (1O2) detection that provides necessary therapeutic feedback into nanotheranostics for hypoxic tumor photodynamic therapy (PDT) is desirable but still challenging. Herein, we report a nanosensor (denominated PAPD) by combining dual-channel ratiometric sensing and oxygen-augmenting strategies, which synergistically realizes real-time 1O2 self-detection, O2 self-supply and enhanced phototherapy. PAPD nanosensor is constructed by encapsulating anthracene-based 1O2 sensitive fluorophore (DPA) into porphyrin metal-organic frameworks (PCN-224), decorating gold nanoparticles (AuNPs) as nanoenzymes, and coating polyethylene glycol thiol (PEG-SH) by the Au–S bond. PCN-224 serves as 1O2 reference fluorescence (FL) agent and photosensitizer. Once PCN-224-induced 1O2 is synthesized, the dual-channel ratiometric FL signal of PAPD actualizes sensitive, accurate and dynamic 1O2 visualization and gives real-time therapeutic information correlated with the therapeutic progression. Additionally, the catalase-like activity of PAPD possesses in situ O2 production via intracellular H2O2 decomposition and accelerates 1O2 yields for amplifying the tumor cell killing efficiency. Moreover, the ratiometric 1O2 self-detection affords the capacity to evaluate the O2 self-supplying effect in tumor 4T1 cells. Consequently, the rational-designed nanosensor PAPD provides a paradigm for real-time therapeutic evaluation and precise hypoxic tumor treatment clinically.

Mn3 O4 Nanoshell Coated Metal-Organic Frameworks with Microenvironment-Driven O2 Production and GSH Exhaustion Ability for Enhanced Chemodynamic and Photodynamic Cancer Therapies.

Nanomedicine exhibits emerging potentials to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC). Nevertheless, it is still difficult to develop a precise codelivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 is selected as the carrier to enable effective cancer therapy through light-activated reactive oxygen species (ROS) formation, and the PCN-224@Mn3 O4 @HA is created in a simple one-step process by coating Mn3 O4 nanoshells on the PCN-224 template, which can then be used as an "ROS activator" to exert catalase- and glutathione peroxidase-like activities to alleviate tumor hypoxia while reducing tumor reducibility, leading to improved photodynamic therapeutic (PDT) effect of PCN-224. Meanwhile, Mn2+ produced cytotoxic hydroxyl radicals (∙OH) via the Fenton-like reaction, thus producing a promising spontaneous chemodynamic therapeutic (CDT) effect. Importantly, by remodeling the tumor microenvironment(TME), Mn3 O4 nanoshells downregulated hypoxia-inducible factor 1α expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light-controlled ROS formation and multimodality imaging abilities, can effectively inhibit tumor proliferation through synergisticPDT/CDT, and prevent tumor resurgence by remodeling TME.