CRISPR/Cas9 and Chlorophyll Coordination Micelles for Cancer Treatment by Genome Editing and Photodynamic Therapy.

CRISPR/Cas9-based gene therapy and photodynamic therapy both show promise for cancer treatment but still have their drawbacks limited by tumor microenvironment and long treatment duration. Herein, CRISPR/Cas9 genome editing and photodynamic strategy for a synergistic anti-tumor therapeutic modality is merged. Chlorophyll (Chl) extracted from natural green vegetables is encapsulated in Pluronic F127 (F127) micelles and Histidine-tagged Cas9 can be effectively chelated onto micelles via metal coordination by simple incubation, affording Cas9-Chl@F127 micelles. Mg2+ acts as an enzyme cofactor to correlatively enhance Cas9 gene-editing activity. Upon laser irradiation, Chl as an effective photosensitizer generates reactive oxygen species (ROS) to kill tumor cells. Meanwhile, CRISPR/Cas9, mediated by dual deliberately designed gRNAs of APE1 and NRF2, can reprogram the tumor microenvironment by increasing the intracellular oxygen accumulation and impairing the oxidative defense system of tumor cells. Cas9-Chl@F127 micelles can responsively release Cas9 in the presence of abundant ATP or low pH in tumor cells. In a murine tumor model, Cas9-Chl@F127 complexed with dual gRNAs including APE1 and NRF2 significantly inhibits the tumor growth. Taken together, Cas9-Chl@F127 micelles, representing the first Chl-based green biomaterial for the delivery of Cas9, show great promise for the synergistic anti-tumor treatment by PDT and gene editing.

Orally-Delivered, Cytokine-Engineered Extracellular Vesicles for Targeted Treatment of Inflammatory Bowel Disease.

The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal-IL10-EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal-IL10-EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal-IL10-EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal-IL10-EVs (C/A) features biocompatibility, pH-responsive drug release, and macrophage-targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.

Anti-Tumor Immunity Induced by a Ternary Membrane System Derived From Cancer Cells, Dendritic Cells, and Bacteria.

Cancer vaccines generally are limited by insufficient tumor-specific cellular immunogenicity. Herein, a potent "ABC" ternary membrane-derived vaccine system blended from antigen-presenting mature dendritic cell membranes ("A"), bacterial E. coli cytoplasmic membranes ("B"), and cancer cell membranes ("C") is developed using a block-copolymer micelle-enabled approach. The respective ABC membrane components provide for a source of cellular immune communication/activation and enhanced accumulation in lymph nodes (A), immunological adjuvant (B), and tumor antigens (C). The introduction of dendritic cell (DC) membranes enables multiple cell-to-cell communication and powerful immune activation. ABC activates dendritic cells and promotes T-cell activation and proliferation in vitro. In vivo, ABC is 14- and 304-fold more immunogenic than binary (BC) and single (C) membrane vaccines, and immunization with ABC enhances the frequency of tumor-specific cytotoxic T lymphocytes, leading to an 80% cure rate in tumor-bearing mice. In a surgical resection and recurrence model, ABC prevents recurrence with vaccination from autologous cancer membranes, and therapeutic effects are observed in a lung metastasis model even with heterologous cancer cell membranes. ABCs formed from human cancer patient-derived tumor cells activate human monocyte-derived dendritic cells (moDC). Taken together, the ternary ABC membrane system provides the needed functional components for personalized cancer immunotherapy.

Circ_0027470 promotes cadmium exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and stimulating SHH signaling pathway.

Cadmium (Cd) is a toxic heavy metal pollutant and serves as an important environmental endocrine-disrupting chemical. Cd exposure is believed to can enhance the risks of age-related disorders including benign prostatic hyperplasia (BPH). This study was to investigate the harms of Cd exposure on mice prostate and human nonmalignant prostate epithelial RWPE-1 cells. Mice prostate fibrosis was evaluated by visualizing the prostatic collagen deposition via Masson and Sirius red staining, and detecting the content of hydroxyproline. Additionally, the epithelial-mesenchymal transition (EMT), primary ciliogenesis and SHH signaling pathways in both mice prostate and RWPE-1 cells were evaluated. It was found that Cd exposure stimulated prostatic collagen deposition, EMT and primary ciliogenesis, as well as enhanced the circ_0027470 level and reduced the miRNA-1236-3p level. Circ_0027470 functioned as a sponge of miRNA-1236-3p, which had the inhibiting target of SHH. The whole results showed that circ_0027470 promoted Cd exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and subsequently stimulating SHH signaling pathway. This study shed a light on a novel molecular mechanism involved in circRNA for Cd exposure-induced prostate deficits.

Impacts of pollution heterogeneity on population exposure in dense urban areas using ultra-fine resolution air quality data.

Traditional air quality data have a spatial resolution of 1 km or above, making it challenging to resolve detailed air pollution exposure in complex urban areas. Combining urban morphology, dynamic traffic emission, regional and local meteorology, physicochemical transformations in air quality models using big data fusion technology, an ultra-fine resolution modeling system was developed to provide air quality data down to street level. Based on one-year ultra-fine resolution data, this study investigated the effects of pollution heterogeneity on the individual and population exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3) in Hong Kong, one of the most densely populated and urbanized cities. Sharp fine-scale variabilities in air pollution were revealed within individual city blocks. Using traditional 1 km average to represent individual exposure resulted in a positively skewed deviation of up to 200% for high-end exposure individuals. Citizens were disproportionally affected by air pollution, with annual pollutant concentrations varied by factors of 2 to 5 among 452 District Council Constituency Areas (DCCAs) in Hong Kong, indicating great environmental inequities among the population. Unfavorable city planning resulted in a positive spatial coincidence between pollution and population, which increased public exposure to air pollutants by as large as 46% among districts in Hong Kong. Our results highlight the importance of ultra-fine pollutant data in quantifying the heterogeneity in pollution exposure in the dense urban area and the critical role of smart urban planning in reducing exposure inequities.

Surfactant-Stripped Semiconducting Polymer Micelles for Tumor Theranostics and Deep Tissue Imaging in the NIR-II Window.

Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.

Colistin Crosslinked Gemcitabine Micelles to Eliminate Tumor Drug Resistance Caused by Intratumoral Microorganisms.

In the tumor microenvironment, there exist microorganisms that metabolize anticancer drugs, leading to chemotherapy failure. To solve this problem, herein, we develop antibiotic and anticancer drug co-delivery micelles, termed colistin crosslinked gemcitabine micelle (CCGM). A self-immolative linker enables colistin and gemcitabine to be released on demand without affecting their antibacterial and anticancer effects. Once CCGM is delivered to the tumor microenvironment, intracellular glutathione triggers the release of colistin and gemcitabine, inhibiting the growth of microbes in the tumor, thus eliminating the microbe-induced drug resistance of tumor.

In Situ Collection and Rapid Detection of Pathogenic Bacteria Using a Flexible SERS Platform Combined with a Portable Raman Spectrometer.

This study aims to develop a simple, sensitive, low-cost, environmentally friendly and flexible surface-enhanced Raman scattering (SERS) platform, combined with a portable Raman spectrometer, for the rapid and on-site SERS detection of bacteria. Commercial tobacco packaging paper (TPP) with little background interference was used as a loading medium that effectively adsorbed Au nanoparticles and provided sufficient "hot spots". This Au-tobacco packaging paper (Au-TPP) substrate used as a flexible SERS platform can maximize sample collection by wiping irregular surfaces, and was successfully applied to the on-site and rapid detection of pathogenic bacteria. Raman fingerprints of pathogenic bacteria can be obtained by SERS detection of spiked pork using wipeable Au-TPP, which verifies its value in practical applications. The results collected by SERS were further verified by polymerase chain reaction (PCR) results. It showed several advantages in on-site SERS detection, including accurate discrimination, simple preparation, easy operation, good sensitivity, accuracy and reproducibility. This study indicates that the established flexible SERS platform has good practical applications in pathogenic bacterial identification and other rapid detections.

Rapid Detection of Aspergillus flavus and Quantitative Determination of Aflatoxin B1 in Grain Crops Using a Portable Raman Spectrometer Combined with Colloidal Au Nanoparticles.

Aspergillus flavus and Aflatoxins in grain crops give rise to a serious threat to food security and cause huge economic losses. In particular, aflatoxin B1 has been identified as a Class I carcinogen to humans by the International Agency for Research on Cancer (IARC). Compared with conventional methods, Surface-Enhanced Raman Scattering (SERS) has paved the way for the detection of Aspergillus flavus and Aflatoxins in grain crops as it is a rapid, nondestructive, and sensitive analytical method. In this work, the rapid detection of Aspergillus flavus and quantification of Aflatoxin B1 in grain crops were performed by using a portable Raman spectrometer combined with colloidal Au nanoparticles (AuNPs). With the increase of the concentration of Aspergillus flavus spore suspension in the range of 102-108 CFU/mL, the better the combination of Aspergillus flavus spores and AuNPs, the better the enhancement effect of AuNPs solution on the Aspergillus flavus. A series of different concentrations of aflatoxin B1 methanol solution combined with AuNPs were determined based on SERS and their spectra were similar to that of solid powder. Moreover, the characteristic peak increased gradually with the increase of concentration in the range of 0.0005-0.01 mg/L and the determination limit was 0.0005 mg/L, which was verified by HPLC in ppM concentration. This rapid detection method can greatly shorten the detection time from several hours or even tens of hours to a few minutes, which can help to take effective measures to avoid causing large economic losses.

Sweet Sorghum Originated through Selection of Dry, a Plant-Specific NAC Transcription Factor Gene.

Sorghum (Sorghum bicolor) is the fifth most popular crop worldwide and a C4 model plant. Domesticated sorghum comes in many forms, including sweet cultivars with juicy stems and grain sorghum with dry, pithy stems at maturity. The Dry locus, which controls the pithy/juicy stem trait, was discovered over a century ago. Here, we found that Dry gene encodes a plant-specific NAC transcription factor. Dry was either deleted or acquired loss-of-function mutations in sweet sorghum, resulting in cell collapse and altered secondary cell wall composition in the stem. Twenty-three Dry ancestral haplotypes, all with dry, pithy stems, were found among wild sorghum and wild sorghum relatives. Two of the haplotypes were detected in domesticated landraces, with four additional dry haplotypes with juicy stems detected in improved lines. These results imply that selection for Dry gene mutations was a major step leading to the origin of sweet sorghum. The Dry gene is conserved in major cereals; fine-tuning its regulatory network could provide a molecular tool to control crop stem texture.

Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment.

Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The stimuli used for activation are based on differences between the environment of the diseased or targeted sites, and normal tissues. Endogenous stimuli include pH, redox reactions, enzymatic activity, temperature and others. Exogenous site-specific stimuli include the use of magnetic fields, light, ultrasound and others. These endogenous or exogenous stimuli lead to structural changes or cleavage of the cargo carrier, leading to release of the API. A wide variety of stimulus-responsive systems have been developed-responsive to both a single stimulus or multiple stimuli-and represent a theranostic tool for disease treatment. In this review, stimuli commonly used in the development of theranostic nanoplatforms are enumerated. An emphasis on chemical structure and property relationships is provided, aiming to focus on insights for the design of stimulus-responsive delivery systems. Several examples of theranostic applications of these stimulus-responsive nanomedicines are discussed.

A surfactant-stripped cabazitaxel micelle formulation optimized with accelerated storage stability.

Pluronic (Poloxomer) micelles can solubilize cabazitaxel (CTX), a second-generation taxane, and then be subjected to low-temperature "surfactant-stripping" to selectively remove loose and free surfactant, thereby increasing the drug-to-surfactant ratio. We previously found that the addition of certain other co-loaded hydrophobic cargo to the micelles can result in stabilized, surfactant-stripped cabazitaxel (sss-CTX) micelles, which resist drug aggregation in aqueous storage, a common challenge for taxanes. Here, we show that elevated temperatures can accelerate the aggregation of sss-CTX micelles, thereby enabling rapid optimization of formulations with respect to the type and ratio of co-loader used for stabilization. A sss-CTX micelle formulation was developed using mifepristone as the co-loader, at a 60% mass ratio to the CTX. Drug release, hemolysis and complement activation were investigated in vitro. Microtubule stabilization and in vitro cytotoxicity were similar for sss-CTX and a conventional Tween-80 micelle formulation. In vivo pharmacokinetics also revealed similar blood circulation of the two formulations. In subcutaneous Lewis lung carcinoma tumors, as well as in an aggressive mouse model of malignant pleural effusion, sss-CTX showed a similar therapeutic effect as the Tween-80 based formulation. Altogether, these data show that sss-CTX can achieve similar efficacy as conventional Tween-80 formulations, albeit with substantially higher drug-to-surfactant ratio and with capability of extended aqueous storage.

Ingestible Contrast Agents for Gastrointestinal Imaging.

Gastrointestinal (GI) ailments cover a wide variety of diseases involving the esophagus, stomach, small intestine, large intestine, and rectum. They bring about many inconveniences in daily life in chronic diseases and can even be life threatening in acute cases. Rapid and safe detection approaches are essential for early diagnosis and timely management. Contrast agents for GI imaging can enhance contrast to distinguish abnormal lesions from normal structures. Computed tomography and magnetic resonance imaging are two important diagnostic tools for the evaluation of GI conditions. This review mainly involves several common GI diseases, including inflammatory diseases, intestinal tumors, diarrhea, constipation, and gastroesophageal reflux diseases. Selected contrast agents, such as barium sulfate, iodine-based agents, gadolinium-based agents, and others, are summarized. Going forward, continued endeavors are being made to develop more emerging contrast agents for other imaging modalities.

Encapsulation of AgNPs within Zwitterionic Hydrogels for Highly Efficient and Antifouling Catalysis in Biological Environments.

Silver nanoparticles (AgNPs) have been widely used as catalysts in a variety of chemical reactions owing to their unique surface and electronic properties, but their practical applications have been hindered by severe aggregation. The immobilization of AgNPs is crucial to preventing their aggregation or precipitation as well as to improving their reusability. Herein, we developed a facile route for the reductant-free in situ synthesis of AgNPs in zwitterionic hydrogels. Via this method, the embedded AgNPs had a uniform distribution, high activity, and antibiofouling capability. The catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) using polycarboxybetaine-AgNPs (PCB-AgNPs) could achieve >95% conversion efficiency within 5 min. Meanwhile, the normalized rate constant knor (10.617 s-1mmol-1) was higher than that of most of the reported immobilized nanocatalysts. More importantly, in a biofouling environment, PCB-AgNPs could still exhibit >97% initial catalytic activity while AgNPs in the PSB or PHEMA hydrogel lost ∼60% activity. This strategy holds great potential for the immobilization of nanoparticle catalysts, especially for applications in biological environments.

Slit-enabled linear-array photoacoustic tomography with near isotropic spatial resolution in three dimensions.

Due to its unique capability of visualizing optical absorption in deep tissues, photoacoustic tomography is increasingly used in biomedical imaging. Among various types of transducer arrays, the linear array is perhaps the most widely used in photoacoustic tomography because it is commercially available and readily allows ultrasound imaging. However, the three-dimensional imaging capability of a linear array is limited due to its poor elevational resolution. While various scanning schemes have been proposed to address this problem, they all suffer from long scanning time to the best of our knowledge. To address this issue, we introduce slit-enabled three-dimensional photoacoustic tomography. The metal slit, placed at the array focus, causes the incoming photoacoustic waves to diffract along the elevation direction and, hence, significantly improves the elevation detection aperture and resolution. We tested the new system in both phantoms and animals. The slit improves the elevation resolution by 10 times without compromising scanning time.

Sulfonated Polyethylenimine for Photosensitizer Conjugation and Targeting.

Polysulfonated macromolecules are known to bind selectins, adhesion membrane proteins which are broadly implicated in inflammation. Commercially available branched polyethylenimine (PEI) was reacted with chlorosulfonic acid to generate sulfonated PEI with varying degrees of sulfonation. Remaining unreacted amine groups were then used for straightforward conjugation with pyropheophoribide-a, a near-infrared photosensitizer. Photosensitizer-labeled sulfonated PEI conjugates inhibited blood coagulation and were demonstrated to specifically bind to cells genetically programmed to overexpress L-selectin (CD62L) or P-selectin (CD62P). In vitro, following targeting, selectin-expressing cells could be destroyed via photodynamic therapy.

Stability and genetic control of morphological, biomass and biofuel traits under temperate maritime and continental conditions in sweet sorghum (Sorghum bicolour).

KEY MESSAGE: Eight morphological, biomass and biofuel traits were found with high broad-sense heritability and 18 significant QTLs discovered including one locus controlling the stem juice trait for sorghum grown in Denmark and China. Sweet sorghum with tall plant, fast maturation and high stem Brix content can be bred as a biofuel crop for Northern Europe. Sweet sorghum (Sorghum bicolour), a native tropical C4 crop, has attracted interest as a bioenergy crop in northern countries due to its juice-rich stem and high biomass production. Little is known about the traits important for its adaptation to high altitude climatic conditions and their genetic controls. Recombinant inbred lines derived from a cross between a sweet and a grain kaoliang sorghum were used in five field trials in Denmark and in China to identify the stability and genetic controls of morphological, biomass and biofuel traits during three consecutive summers with short duration, cool temperatures and long days. Eight out of 15 traits were found with high broad-sense heritability. Strong positive correlations between plant height and biomass traits were observed, while Brix and juice content were under different genetic controls. Using newly developed PAV (presence and absence variant) markers, 53 QTLs were detected, of which 18 were common for both countries, including a locus controlling stem juice (LOD score = 20.5, r (2) = 37.5 %). In Denmark, the heading stage correlated significantly with biomass and morphology traits, and two significant maturity QTLs detected on chromosomes SBI01 and SBI02 co-localised with QTLs previously associated with early-stage chilling tolerance, suggesting that accelerating maturation might be a means of coping with low-temperature stress. Our results suggest that selection for tall and fast maturating sorghum plants combined with high Brix content represents a high potential for breeding bioenergy crop for Northern Europe.

Reversible Micro- and Nano- Phase Programming of Anthraquinone Thermochromism Using Blended Block Copolymers.

Here, we present an approach to generate materials with programmable thermochromic transition temperatures (TTTs), based on the reversible microcrystallization of anthraquinone dyes with the assistance of blended Pluronic block copolymers. At temperatures above block copolymer critical micellization temperature (CMT), hydrophobic anthraquinone dyes, including Sudan blue II, were dispersed in copolymer micelles, whereas at lower temperature, the dyes formed microcrystals driven by dye-dye and dye-Pluronic molecular interactions. The crystallization process altered the optical properties of the dye with bathochromatic shifts detectable by eye and the thermochromic process was fully reversible. Not only could Pluronic reversibly incorporate the anthraquinone dyes into micelles at elevated temperatures, but it also modulated the crystallization process and resulting morphology of microcrystals via tuning the molecular interactions when the temperature was lowered. Crystal melting transition points (and TTTs) were in agreement with the CMTs, demonstrating that the thermochromism was dependent on block copolymer micellization. Thermochromism could be readily programmed over a broad range of temperatures by changing the CMT by using different types and concentrations of Pluronics and combinations thereof.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.

Oxygen Self-Supplied Perfluorocarbon-Modified Micelles for Enhanced Cancer Photodynamic Therapy and Ferroptosis.

Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127. The PFCs on the surface of the micelle play a crucial role in efficiently solubilizing and delivering oxygen as well as increasing the hydrophobicity of the micelle surface, giving rise to enhanced endocytosis by cancer cells. The incorporation of an oxygen-carrying moiety into the micelles enhances the therapeutic impact of PDT and ferroptosis, leading to amplified endocytosis and cytotoxicity of tumor cells. Hypotonic saline technology was developed to enhance the cargo encapsulation efficiency. Notably, in a murine tumor model, Ce6-Sor@PFC-F127 effectively inhibited tumor growth through the combined use of oxygen-enhanced PDT and ferroptosis. Taken together, this work underscores the promising potential of Ce6-Sor@PFC-F127 as a multifunctional therapeutic nanoplatform for the codelivery of multiple cargos such as oxygen, photosensitizers, and ferroptosis inducers.