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.

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.

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.

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.

Light-Activatable Synergistic Therapy of Drug-Resistant Bacteria-Infected Cutaneous Chronic Wounds and Nonhealing Keratitis by Cupriferous Hollow Nanoshells.

Due to the inability to spontaneously heal and vulnerability to bacterial infection, diabetic patients are frustrated by unexpected epithelium injuries in daily life. Notably, a drug-resistant bacterial infection may result in a long-term impact to the natural function of damaged organs. It is imperative to develop strategies that promote injury recovery and eradicate drug-resistant infection simultaneously. Here, we present a composite structured cupriferous hollow nanoshell (AuAgCu2O NS) that consists of a hollow gold-silver (AuAg) core and Cu2O shell as a photothermal therapeutic agent for a cutaneous chronic wound and nonhealing keratitis with drug-resistant bacterial infection. The controllable photothermal therapeutic effect and released silver ion from the hollow AuAg core possess a synergistic effect to eradicate multi-drug-resistant bacteria, including extended-spectrum ß-lactamase Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Meanwhile, the released copper ion from the Cu2O shell could expedite endothelial cell angiogenesis and fibroblast cell migration, thus boosting wound-healing effects. In both infection-complicated disease models, the ophthalmic clinical score, wound closure rates, and histopathology analysis demonstrate that the AuAgCu2O NSs could facilitate the re-epithelialization at the wound area and eliminate the complicated bacterial infection from diabetic mice. A primary signal path involved in the promoted healing effect was further illustrated by comprehensive assays of immunohistochemical evaluation, Western blot, and quantitative polymerase chain reaction. Taken together, our AuAgCu2O NSs are shown to be potent candidates for clinical utilization in the treatment of diabetic epithelium injuries.

Laser-triggered aggregated cubic α-Fe2O3@Au nanocomposites for magnetic resonance imaging and photothermal/enhanced radiation synergistic therapy.

Theranostic nanoparticles (NPs) have recently generated substantial interest in translational cancer research due to their capabilities for multimodal diagnostic imaging and anti-cancer therapy. We herein developed cubic alpha-iron(III) oxide (α-Fe2O3) nanoparticles coated with ultrasmall gold nanoseeds, abbreviated as α-Fe2O3@Au, for the synergistic treatment of radiotherapy and photothermal therapy in breast cancer. The resultant NPs, with an average diameter of 49 nm, exhibited satisfactory biosafety profiles and provided tumor contrast in T2-weighted magnetic resonance (MR) imaging. The coating of ultrasmall Au nanoseeds exhibited strong absorption of near-infrared (NIR) laser that enabled to an efficacious photothermal therapy. It also sensitized radiotherapy, X-ray in this study, by generating large quantities of tumoricidal reactive oxygen species (ROS). Moreover, with the aid of NIR laser irradiation, the α-Fe2O3 substrate showed partial ablation and the Au NPs on its surface aggregated into a larger size (~13 nm), which has been proven to be the optimized size for radiotherapy. When tested in 4T1 murine breast cancer model, the α-Fe2O3@Au NPs significantly suppressed tumor growth (P < 0.01) when irradiated with a low-power laser (1.5 W/cm2 for 3 min) and an intermediate X-ray dose (6 Gy). Our results demonstrate that α-Fe2O3@Au, integrated with MRI, photothermal therapy, and radiosensitization, is a promising multifunctional theranostic nanomedicine for clinical applications.