Doxorubicin-Loaded Microalgal Delivery System for Combined Chemotherapy and Enhanced Photodynamic Therapy of Osteosarcoma.

Osteosarcoma (OS) is considered the most frequent type of primary malignant bone tumor. Currently, radiotherapy, photodynamic (PDT), and other therapies for osteosarcoma are limited by tumor hypoxia and single efficacy and serve side-effects. Herein, we reported a microalgal drug delivery system (SpiD), doxorubicin (DOX)-loaded Spirulina platensis (Spi) for OS therapy. The specific surface of Spirulina platensis allowed for effective loading of DOX via surface channels and electrostatic interactions. Under 650 nm laser irradiation, SpiD enabled high oxygen production by photosynthesis and enhanced reactive oxygen species (ROS) generation via chlorophyll-assisted photosensitization, synergistically killing tumor cells with the released DOX. Combined chemotherapy and enhanced PDT mediated by SpiD exerted synergic antitumor effects and resulted in potent therapeutic efficacy in orthotopic osteosarcoma mice. Furthermore, SpiD could reduce the side-effects of chemotherapy, showing excellent blood and tissue safety. Taken together, this microalgal drug delivery system provided a natural, efficient, safe, and inexpensive strategy for OS treatment.

Microalgae-Based Hydrogel for Inflammatory Bowel Disease and Its Associated Anxiety and Depression.

Patients diagnosed with inflammatory bowel disease (IBD) exhibit a notable prevalence of psychiatric disorders, such as anxiety and depression. Nevertheless, the etiology of psychiatric disorders associated with IBD remains uncertain, and an efficacious treatment approach has yet to be established. Herein, an oral hydrogel strategy (SP@Rh-gel) is proposed for co-delivery of Spirulina platensis and rhein to treat IBD and IBD-associated anxiety and depression by modulating the microbiota-gut-brain axis. SP@Rh-gel improves the solubility, release characteristics and intestinal retention capacity of the drug, leading to a significant improvement in the oral therapeutic efficacy. Oral administration of SP@Rh-gel can reduce intestinal inflammation and rebalance the disrupted intestinal microbial community. Furthermore, SP@Rh-gel maintains intestinal barrier integrity and reduces the release of pro-inflammatory factors and their entry into the hippocampus through the blood-brain barrier, thereby inhibiting neuroinflammation and maintaining neuroplasticity. SP@Rh-gel significantly alleviates the colitis symptoms, as well as anxiety- and depression-like behaviors, in a chronic colitis mouse model. This study demonstrates the significant involvement of the microbiota-gut-brain axis in the development of IBD with psychiatric disorders and proposes a safe, simple, and highly efficient therapeutic approach for managing IBD and comorbid psychiatric disorders.

Bioinspired pH-Responsive Microalgal Hydrogels for Oral Insulin Delivery with Both Hypoglycemic and Insulin Sensitizing Effects.

The oral form of insulin is more convenient and has better patient compliance than subcutaneous or intravenous insulin. Current oral insulin preparations, however, cannot overcome the enzyme barrier, chemical barrier, and epithelial barrier of the gastrointestinal tract completely. In this study, a microalgae-based oral insulin delivery strategy (CV@INS@ALG) was developed using Chlorella vulgaris (CV)-based insulin delivery system cross-linking with sodium alginate (ALG). CV@INS@ALG could overcome the gastrointestinal barrier, protect insulin from harsh gastric conditions, and achieve a pH-responsive drug release in the intestine. CV@INS@ALG might contribute to two mechanisms of insulin absorption, including direct insulin release from the delivery system and endocytosis by M cells and macrophages. In the streptozotocin (STZ)-induced type 1 diabetic mouse model, CV@INS@ALG showed a more effective and long-lasting hypoglycemic effect than direct insulin injection and did not cause any damage to the intestinal tract. Additionally, the long-term oral administration of the carrier CV@ALG effectively ameliorated gut microbiota disorder, and significantly increased the abundance of probiotic Akkermansia in db/db type 2 diabetic mice, thereby enhancing the insulin sensitivity of mice. Microalgal insulin delivery systems could be degraded and metabolized in the intestinal tract after oral administration, showing good biodegradability and biosafety. This insulin delivery strategy based on microalgal biomaterials provides a natural, efficient, and multifunctional solution for oral insulin delivery.

A biodegradable, flexible photonic patch for in vivo phototherapy.

Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.

[UGT1A1 gene mutations in Chinese Dong neonates in Sanjiang, Guangxi]. / 广西三江县侗族新生儿UGT1A1åŸºå› å˜å¼‚åˆ†æž.

OBJECTIVES: To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates. METHODS: A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced. RESULTS: In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05). CONCLUSIONS: UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.

Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin.

We aimed to investigate the effect of the genetic mutant G71R (c. 211G > A) in uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) on the glucuronidation of unconjugated bilirubin. The UGT1A1 wild-type and mutant G71R gene sequences were inserted into the lentiviral vector GV358 plasmid and then transfected into COS-7 cells. Real-time polymerase chain reaction and western blot analyses were used to determine mRNA and protein expression levels of UGT1A1, respectively. High-performance liquid chromatography was used to quantitate the levels of conjugated bilirubin. The results showed no significant difference in the mRNA and protein expression levels between the UGT1A1 wild-type and G71R homozygous and heterozygous mutants. The level of conjugated bilirubin reached a maximum in wild-type UGT1A1-transfected COS-7 cells. However, relative to the UGT1A1 wild-type, conjugated bilirubin concentrations were 71 and 22% with G71R heterozygous- and G71R homozygous-transfected COS-7 cells, respectively. In conclusion, we successfully established in vitro cell models of the UGT1A1 wild-type and the G71R homozygous and heterozygous mutants using a lentiviral vector. Furthermore, the catalytic activity for unconjugated bilirubin was lower in the mutant G71R than the UGT1A1 wild-type enzyme, and a weaker effect was observed in the homozygote.

Microalgae-based oral microcarriers for gut microbiota homeostasis and intestinal protection in cancer radiotherapy.

Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.

Aggregation-induced emission luminogens for image-guided surgery in non-human primates.

During the past two decades, aggregation-induced emission luminogens (AIEgens) have been intensively exploited for biological and biomedical applications. Although a series of investigations have been performed in non-primate animal models, there is few pilot studies in non-human primate animal models, strongly hindering the clinical translation of AIE luminogens (AIEgens). Herein, we present a systemic and multifaceted demonstration of an optical imaging-guided surgical operation via AIEgens from small animals (e.g., mice and rabbits) to rhesus macaque, the typical non-human primate animal model. Specifically, the folic conjugated-AIE luminogen (folic-AIEgen) generates strong and stable fluorescence for the detection and surgical excision of sentinel lymph nodes (SLNs). Moreover, with the superior tumor/normal tissue ratio and rapid tumor accumulation, folic-AIEgen successfully images and guides the precise resection of invisible cancerous metastases. Taken together, the presented strategies of folic-AIEgen based fluorescence intraoperative imaging and visualization-guided surgery show potential for clinical applications.

Orally deliverable strategy based on microalgal biomass for intestinal disease treatment.

Design of innovative strategies for oral drug delivery is particularly promising for intestinal disease treatment. However, many obstacles such as poor therapeutic efficacy and low bioavailability and biocompatibility remain to be addressed. Here, we report a versatile formulation based on a helical-shaped cyanobacterium, Spirulina platensis (SP), loaded with curcumin (SP@Curcumin) for the treatment of colon cancer and colitis, two types of intestinal diseases. In radiotherapy for colon cancer, SP@Curcumin could mediate combined chemo- and radiotherapy to inhibit tumor progression while acting as a radioprotector to scavenge reactive oxygen species induced by the high dose of x-ray radiation in healthy tissues. SP@Curcumin could also reduce the production of proinflammatory cytokines and thereby exerted anti-inflammatory effects against colitis. The oral drug delivery system not only leveraged the biological properties of microalgal carriers to improve the bioavailability of loaded drugs but also performed excellent antitumor and anti-inflammation efficacy for intestinal disease treatment.

A Cross-Sectional Nationwide Study on Accessibility and Availability of Neonatal care Resources in Hospitals of China: Current Situation, Mortality and Regional Differences: Neonatal Care Resources and Newborn Mortality in China.

BACKGROUND: To investigate the current situation of neonatal care resources (NCR), newborn mortality rates (NMR), regional differences and existing challenges in China. METHODS: By using a self-designed questionnaire form and the cross-sectional method, we conducted a survey of all hospitals equipped with neonatal facilities in China from March 2019 to March 2020 with respect to the level and nature of these hospitals, the number of newborn beds and NICU beds, the number of neonatal pediatricians, and the development of therapeutic techniques. The data about the newborn births and deaths were retrieved from the annual statistics of the health commissions of the related provinces, autonomous regions and municipalities. FINDING: Included in this nationwide survey were 3,020 hospitals from all 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government of Mainland China, with a 100% response rate. They included 1,183 (39.2%) level-3 (L3) hospitals, 1629 (53.9%) L-2 hospitals and 208 (6.9%) L-1 hospitals. Geographically, 848 (31.4%) hospitals were distributed in Central China, 983 (32.5%) hospitals in East China, and 1,089 (36.1%) in West China. The 3,020 included hospitals were altogether equipped with 75,679 newborn beds, with a median of 20 (2-350) beds, of which 2,286 hospitals (75.7%) were equipped with neonatal intensive care units (NICU), totaling 28,076 NICU beds with a median of 5 (1-160) beds. There were altogether 27,698 neonatal pediatricians in these hospitals, with an overall doctor-bed ratio of 0.366. There were 48.18 newborn beds and 17.87 NICU beds per 10,000 new births in China. In East, Central and West China, the number of neonatal beds, NICU beds, neonatal pediatricians, and attending pediatricians or pediatricians with higher professional titles per 10,000 newborns was 42.57, 48.64 and 55.67; 17.07, 18.66 and 18.17; 16.26, 16.51 and 20.81; and 10.69, 10.81 and 11.29, respectively. However, when the population and area are taken into consideration and according to the health resources density index (HRDI), the number of newborn beds, NICU beds and neonatal pediatricians in West China was significantly lower than that in Central and East China. In addition, only 10.64% of the neonatal pediatricians in West China possessed the Master or higher degrees, vs. 31.7% in East China and 20.14% in Central China. On the contrary, the number of neonatal pediatricians with a lower than Bachelor degree in West China was significantly higher than that in Central and East China (13.28% vs. 7.36% and 4.28%). Technically, the application rate of continuous positive airway pressure (CPAP) and conventional mechanical ventilation (CMV) in L-1 hospitals of West China was lower than that in Central and East China. According to the statistics in 2018, the newborn mortality rate (NMR) in West China was significantly higher than that in Central and East China. INTERPRETATION: China has already possessed relatively good resources for neonatal care and treatment, which is the primary reason for the rapid decrease in the NMR in China. However, there are still substantial regional differences. The density of health resources, the level of technical development and educational background of neonatal pediatricians in West China still lag behind those in other regions of China and need to be further improved and upgraded. FUNDING: This research work was funded by National Natural Science Foundation of China (81671504) and United Nations International Children's Emergency Fund (CHINA-UNICEF501MCH).

Research progress on the biomedical application of microalgae.

Microalgae is an easy-to-obtain natural biological material with many varieties and abundant natural reserves. Microalgae are rich in natural fluorescein, which can be used as a contrast agent for fluorescence imaging and photoacoustic imaging for medical imaging. With its active surface, microalgae can effectively adsorb functional molecules, metal elements, etc., and have good application prospects in the field of drug delivery. Microalgae can generate oxygen through photosynthesis to increase local oxygen concentration, reverse local hypoxia to enhance the efficacy of hypoxic tumors and promote wound healing. In addition, microalgae have good biocompatibility, and different administration methods have no obvious toxicity. This paper reviews the research progress on the biomedical application of microalgae in bioimaging, drug delivery, hypoxic tumor treatment, wound healing.

Epigenetics and microRNAs in UGT1As.

UDP-glucuronosyltransferases (UGTs) are the main phase II drug-metabolizing enzymes mediating the most extensive glucuronidation-binding reaction in the human body. The UGT1A family is involved in more than half of glucuronidation reactions. However, significant differences exist in the distribution of UGT1As in vivo and the expression of UGT1As among individuals, and these differences are related to the occurrence of disease and differences in metabolism. In addition to genetic polymorphisms, there is now interest in the contribution of epigenetics and noncoding RNAs (especially miRNAs) to this differential change. Epigenetics regulates UGT1As pretranscriptionally through DNA methylation and histone modification, and miRNAs are considered the key mechanism of posttranscriptional regulation of UGT1As. Both epigenetic inheritance and miRNAs are involved in the differences in sex expression and in vivo distribution of UGT1As. Moreover, epigenetic changes early in life have been shown to affect gene expression throughout life. Here, we review and summarize the current regulatory role of epigenetics in the UGT1A family and discuss the relationship among epigenetics and UGT1A-related diseases and treatment, with references for future research.

Ultrasmall Ga-ICG nanoparticles based gallium ion/photodynamic synergistic therapy to eradicate biofilms and against drug-resistant bacterial liver abscess.

Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics. Here, we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles (ICG-Ga NPs) containing clinically approved gallium (III) (Ga3+) and liver targeting indocyanine green (ICG) molecules to eradicate multi-drug resistant (MDR) bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking. The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane, further boost the endocytosis of Ga3+, then replace iron in bacteria cells to disrupt bacterial iron metabolism, and demonstrate the synergetic bacterial killing and biofilm disrupting effects. The ICG-Ga NPs show an excellent therapeutic effect against extended spectrum ß-lactamases Escherichia coli (ESBL E. coli) and significantly improve treatment outcomes in infected liver abscess and keratitis. Meanwhile, the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route, guaranteeing the biocompatibility. The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.

Calcium phosphate engineered photosynthetic microalgae to combat hypoxic-tumor by in-situ modulating hypoxia and cascade radio-phototherapy.

Rationale: Hypoxia is one of the crucial restrictions in cancer radiotherapy (RT), which leads to the hypoxia-associated radioresistance of tumor cells and may result in the sharp decline in therapeutic efficacy. Methods: Herein, living photosynthetic microalgae (Chlorella vulgaris, C. vulgaris), were used as oxygenators, for in situ oxygen generation to relieve tumor hypoxia. We engineered the surface of C. vulgaris (CV) cells with calcium phosphate (CaP) shell by biomineralization, to form a biomimetic system (CV@CaP) for efficient tumor delivery and in-situ active photosynthetic oxygenation reaction in tumor. Results: After intravenous injection into tumor-bearing mice, CV@CaP could remarkably alleviate tumor hypoxia by continuous oxygen generation, thereby achieving enhanced radiotherapeutic effect. Furthermore, a cascade phototherapy could be fulfilled by the chlorophyll released from photosynthetic microalgae combined thermal effects under 650 nm laser irradiation. The feasibility of CV@CaP-mediated combinational treatment was finally validated in an orthotropic breast cancer mouse model, revealing its prominent anti-tumor and anti-metastasis efficacy in hypoxic-tumor management. More importantly, the engineered photosynthetic microalgae exhibited excellent fluorescence and photoacoustic imaging properties, allowing the self-monitoring of tumor therapy and tumor microenvironment. Conclusions: Our studies of this photosynthetic microsystem open up a new dimension for solving the radioresistance issue of hypoxic tumors.

Intraoperative Assessment and Photothermal Ablation of the Tumor Margins Using Gold Nanoparticles.

Surgical resection is commonly used for therapeutic management of different solid tumors and is regarded as a primary standard of care procedure, but precise localization of tumor margins is a major intraoperative challenge. Herein, a generalized method by optimizing gold nanoparticles for intraoperative detection and photothermal ablation of tumor margins is introduced. These nanoparticles are detectable by highly sensitive surface-enhanced Raman scattering imaging. This non-invasive technique assists in delineating the two surgically challenged tumors in live mice with orthotopic colon or ovarian tumors. Any remaining residual tumors are also ablated by using post-surgical adjuvant photothermaltherapy (aPTT), which results in microscale heat generation due to interaction of these nanoparticles with near-infrared laser. Ablation of these post-operative residual micro-tumors prolongs the survival of mice significantly and delays tumor recurrence by 15 days. To validate clinical translatability of this method, the pharmacokinetics, biodistribution, Raman contrast, aPTT efficiency, and toxicity of these nanoparticles are also investigated. The nanoparticles have long blood circulation time (≈24 h), high tumor accumulation (4.87 ± 1.73%ID g-1) and no toxicity. This high-resolution and sensitive intraoperative approach is versatile and can be potentially used for targeted ablation of residual tumor after resection within different organs.

Non-invasive high-frequency oscillatory ventilation in preterm infants after extubation: a randomized, controlled trial.

OBJECTIVE: To investigate the effectiveness and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) in post-extubation preterm infants. METHODS: This was a randomized, controlled trial. A total of 149 preterm infants aged between 25 to 34 weeks' gestational age with a birth weight of <1500 g who required invasive mechanical ventilation on admission were included. After extubation, they were randomized to the NHFOV group (n = 47), nasal intermittent positive pressure ventilation (NIPPV) group (n = 51), or nasal continuous positive airway pressure (NCPAP) group (n = 51). We compared the effectiveness and safety among these three groups. RESULTS: A total of 139 preterm infants finally completed the study. The reintubation rate was significantly lower in the NHFOV group than in the other groups. The duration of non-invasive ventilation and the length of hospital stay in the NHFOV and NIPPV groups were significantly shorter than those in the NCPAP group. The incidence of bronchopulmonary dysplasia in the NHFOV and NIPPV groups was significantly lower than that in the NCPAP group. The NHFOV group had significantly less nasal injury than the NCPAP group. CONCLUSION: As post-extubation respiratory support in preterm infants, NHFOV has a lower reintubation rate compared with NCPAP and NIPPV, without increasing the rate of complications.

Recent advances in applications of nanoparticles in SERS in vivo imaging.

Surface-enhanced Raman scattering (SERS) technique has been regarded as one of the most important research methods in the field of single-molecule science. Since the previous decade, the application of nanoparticles for in vivo SERS imaging becomes the focus of research. To enhance the performance of SERS imaging, researchers have developed several SERS nanotags such as gold nanostars, copper-based nanomaterials, semiconducting quantum dots, and so on. The development of Raman equipment is also necessary owing to the current limitations. This review describes the recent advances of SERS nanoparticles and their applications for in vivo imaging in detail. Specific examples highlighting the in vivo cancer imaging and treatment application of SERS nanoparticles. A perspective on the challenges and opportunities of nanoparticles in SERS in vivo imaging is also provided. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Cupriferous Silver Peroxysulfite Superpyramids as a Universal and Long-Lasting Agent to Eradicate Multidrug-Resistant Bacteria and Promote Wound Healing.

Because of the emergent evolution of multidrug-resistant (MDR) bacteria, resistance to traditional antibiotics has been increasingly causing public health concerns that it can rapidly overcome the development of antibacterial agents. Here, we demonstrated a facile electrodeposition method to prepare silver peroxysulfite (Ag7O8HSO4, AOHS) superpyramids on band-aids with extraordinary antibacterial performance. The porous structure and the sharp apex of AOHS superpyramids could facilitate the release of high-valence silver ions, which possess highly efficient MDR bacteria-killing effect and keep long-term antibacterial activity (>99% killing efficiency, recycle at least 4 times) because of their superior destruction capability of the membrane of the bacteria. A layer of copper was further evaporated onto the AOHS pyramids decorated on a band-aid, which could promote wound tissue angiogenesis and prohibit bacterial infection simultaneously, and finally accelerate the healing process in MDR bacteria-infected wound in vivo. The simple and low-cost fabrication process, as well as the outstanding antibacterial performance, make AOHS pyramids have promising applications in bacterial infection and practical sterilization fields, especially toward multidrug-resistant bacteria.

Biomineralized Biohybrid Algae for Tumor Hypoxia Modulation and Cascade Radio-Photodynamic Therapy.

Biomineralization of biomaterials has shown extraordinary potential in cancer treatment, but the exploration of their in vivo applications is still insufficient. Here, we report a biohybrid microalgae system using a biomineralization approach to improve their biocompatibility, while keeping their living activities for radiation and photodynamic synergistic therapy in breast cancer. The biohybrid algae (Algae@SiO2) synthesized by a one-step biomimetic silicification method could significantly enhance their cytotoxicity and tolerance, improving the living activity in the tumor area. The innate chlorophyll and unique optical property make Algae@SiO2 possess dual imaging ability, namely, photoacoustic imaging and fluorescence imaging. Algae@SiO2 accumulated in tumor sites could generate oxygen in situ by external light-mediated photosynthesis, relieve tumor hypoxia, and then enhance the efficiency of radiation therapy. As a natural photosensitizer, the released chlorophyll from Algae@SiO2 could provide reactive oxygen species to kill the cancer cells for the cascaded photodynamic therapy. The significant suppression of tumor growth in the mice bearing 4T1 tumor successfully demonstrates the promising anti-tumor effect of the Algae@SiO2-mediated synergistic therapy. Our results show that biohybrid algae, integrated with PAI/FI dual imaging, radiosensitization, and cascaded photothermal therapy, is a promising multifunctional efficient biosystem for cancer treatment.

Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis.

Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation. It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects. Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery. The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag+ and Cu+) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects. The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation. In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model. Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo. Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction. Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball. Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure. Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.