Photocatalytic Antimicrobials: Principles, Design Strategies, and Applications.

Nowadays, the increasing emergence of antibiotic-resistant pathogenic microorganisms requires the search for alternative methods that do not cause drug resistance. Phototherapy strategies (PTs) based on the photoresponsive materials have become a new trend in the inactivation of pathogenic microorganisms due to their spatiotemporal controllability and negligible side effects. Among those phototherapy strategies, photocatalytic antimicrobial therapy (PCAT) has emerged as an effective and promising antimicrobial strategy in recent years. In the process of photocatalytic treatment, photocatalytic materials are excited by different wavelengths of lights to produce reactive oxygen species (ROS) or other toxic species for the killing of various pathogenic microbes, such as bacteria, viruses, fungi, parasites, and algae. Therefore, this review timely summarizes the latest progress in the PCAT field, with emphasis on the development of various photocatalytic antimicrobials (PCAMs), the underlying antimicrobial mechanisms, the design strategies, and the multiple practical antimicrobial applications in local infections therapy, personal protective equipment, water purification, antimicrobial coatings, wound dressings, food safety, antibacterial textiles, and air purification. Meanwhile, we also present the challenges and perspectives of widespread practical implementation of PCAT as antimicrobial therapeutics. We hope that as a result of this review, PCAT will flourish and become an effective weapon against pathogenic microorganisms and antibiotic resistance.

Recent Advances in Hydrogel-Based Phototherapy for Tumor Treatment.

Phototherapeutic agent-based phototherapies activated by light have proven to be safe modalities for the treatment of various malignant tumor indications. The two main modalities of phototherapies include photothermal therapy, which causes localized thermal damage to target lesions, and photodynamic therapy, which causes localized chemical damage by generated reactive oxygen species (ROS). Conventional phototherapies suffer a major shortcoming in their clinical application due to their phototoxicity, which primarily arises from the uncontrolled distribution of phototherapeutic agents in vivo. For successful antitumor phototherapy, it is essential to ensure the generation of heat or ROS specifically occurs at the tumor site. To minimize the reverse side effects of phototherapy while improving its therapeutic performance, extensive research has focused on developing hydrogel-based phototherapy for tumor treatment. The utilization of hydrogels as drug carriers allows for the sustained delivery of phototherapeutic agents to tumor sites, thereby limiting their adverse effects. Herein, we summarize the recent advancements in the design of hydrogels for antitumor phototherapy, offer a comprehensive overview of the latest advances in hydrogel-based phototherapy and its combination with other therapeutic modalities for tumor treatment, and discuss the current clinical status of hydrogel-based antitumor phototherapy.

Near-infrared light and redox dual-activatable nanosystems for synergistically cascaded cancer phototherapy with reduced skin photosensitization.

Currently, activatable photodynamic therapy (PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was "double-locked" by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the "double-key", which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT-PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.

Restorative biodegradable two-layered hybrid microneedles for melanoma photothermal/chemo co-therapy and wound healing.

Tumor killing and wound healing are two complementary and influential processes during the treatment of melanoma. Herein, a two-layered microneedle platform was developed with bifunctional effect of chemo-photothermal synergistic melanoma therapy and skin regeneration. The bifunctional platform composed of embeddable curcumin nanodrugs/new Indocyanine Green/hyaluronic acid (Cur NDs/IR820/HA) microneedles and sodium alginate/gelatin/hyaluronic acid (SA/Ge/HA) supporting backing layer was prepared through a two-step casting process. With uniform incorporation of curcumin nanodrugs and IR820, the microneedles exhibited excellent photothermal performance under external near-infrared (NIR) light stimulation and tumor co-therapy ability. Once the embeddable microneedles were inserted into skin, they would rapidly dissolve and activate drug release successfully for tumor treatment. Moreover, the SA/Ge/HA supporting backing layer was left behind to cover the wound and promote the proliferation of endothelial and fibroblasts cells for enhanced skin regeneration. The two-layered microneedles platform can simultaneously eliminate the tumor and accelerate wounding healing, which may be potentially employed as a competitive strategy for the treatment of melanoma.

Photothermal hydrogel platform for prevention of post-surgical tumor recurrence and improving breast reconstruction.

BACKGROUND: As one of the leading threats for health among women worldwide, breast cancer has high morbidity and mortality. Surgical resection is the major clinical intervention for primary breast tumor, nevertheless high local recurrence risk and breast tissue defect remain two main clinical dilemmas, seriously affecting survival and quality of life of patients. EXPERIMENTAL: We developed a thermoresponsive and injectable hybrid hydrogel platform (IR820/Mgel) by integration of co-loaded porous microspheres (MPs) and IR820 for preventing postoperative recurrence of breast cancer via photothermal therapy and promoting subsequent breast reconstruction. RESULTS: Our results suggested that IR820/Mgel could quickly heated to more than 50.0 â„ƒ under NIR irradiation, enabling killing effect on 4T1 cells in vitro and prevention effect on post-surgical tumor recurrence in vivo. In addition, the hydrogel platform was promising for its minimal invasion and capability of filling irregularly shaped defects after surgery, and the encapsulated MPs could help to increase the strength of gel to realize a long-term in situ function in vivo, and promoted the attachment and anchorage property of normal breast cells and adipose stem cells. CONCLUSIONS: This photothermal hydrogel platform provides a practice paradigm for preventing locally recurrence of breast cancer and a potential option for reconstruction of breast defects.

Near-infrared light-responsive hybrid hydrogels for the synergistic chemo-photothermal therapy of oral cancer.

Light-stimulus-responsive therapies have been recognized as a promising strategy for the efficient and safe treatment of oral squamous cell carcinoma (OSCC). Hydrogels have emerged as a promising multifunctional platform combining localized drug delivery and sustained drug release with multimodal properties for combined OSCC therapy. However, inaccurate drug release and limited light-absorption efficiency have hindered their on-demand chemo-photothermal applications. To tackle these problems, an injectable and near-infrared (NIR) light-responsive hybrid system was developed by incorporating light-responsive mesoporous silica nanoparticles (MSNs) as doxorubicin (DOX) carriers into the IR820/methylcellulose hydrogel networks for chemophotothermal therapy. Under NIR radiation, the incorporated IR820, a new green cyanine dye, was excited to induce photothermal effects against tumor cells. Meanwhile, MSNs achieved self-degradation-controlled DOX release via the cleavage of diselenide bonds induced by reactive oxygen species. Through the combination of chemotherapy and phototherapy, a long-lasting synergistic anti-tumor effect was achieved in vitro and in vivo with less toxicity. These findings demonstrate the potential of light-responsive hydrogels as a multifunctional platform for accurate synergistic chemophotothermal treatment of OSCC.

Curcumin-Microsphere/IR820 Hybrid Bifunctional Hydrogels for In Situ Osteosarcoma Chemo-co-Thermal Therapy and Bone Reconstruction.

Conventional biomaterial-mediated osteosarcoma therapy mainly focuses on its antitumor effect yet often fails to overcome the problem of post-treatment bone tissue defect repair. Simultaneously, minimally invasive drug delivery methods are becoming spotlights for normal tissue preservation. Herein, an injectable curcumin-microsphere/IR820 coloaded hybrid methylcellulose hydrogel (Cur-MP/IR820 gel) platform was designed for osteosarcoma therapy and bone regeneration. In vitro, the K7M2wt osteosarcoma cells were eradicated by hyperthermia and curcumin. Later, the sustained release of curcumin promoted alkaline phosphatase expression and calcium deposition of bone mesenchymal stem cells. In vivo, this hybrid hydrogel could reach tumor site via injection and turned into hydrogel due to heat sensitivity. Under the irradiation of an 808 nm laser, localized hyperthermia (∼51 °C) generated in 5 min to ablate the tumor. Meanwhile, the thermal-accelerated curcumin release and thermal-increased cell membrane permeability led to tumor cell apoptosis. Tumors in photothermal-co-chemotherapy group were successfully restrained from day 2 after treatment. After that, bone reconstruction was promoted because of sustained released curcumin. The chemo-co-thermal efficacy and osteogenic capacity of Cur-MP/IR820 hydrogel suggest a promising approach to the treatment of osteosarcoma and provide provoking inspiration for treating bone tumors and repairing bone tissue.

Magnetic/Gold Core-Shell Hybrid Particles for Targeting and Imaging-Guided Photothermal Cancer Therapy.

The development of hybrid particles for tumor diagnosis and therapy has received considerable attention because they are capable of combining tumor diagnosis and treatment concurrently. So far hybrid particles for efficient and safe tumor theranostics are still very limited. Herein we have designed a new type of hybrid particles and evaluated its potential to be used in image-guided cancer diagnosis and therapy without the need of any toxic anticancer or contrast agents. The hybrid particles, consist of magnetic nanoparticles which are embedded in the poly(methyl methacrylate) (PMMA) cores and gold shells on chitosan (CTS) (γ-Fe2O3 @PMMA/CTS@Au). The hybrid particles were synthesized through initial formation of the core-shell structured γ-Fe2O3 @PMMA/CTS particles containing approximately 20% loading of magnetic nanoparticles. A gold layer was then built on top of the core-shell magnetic particles via a reduction of gold salt by amines from the chitosan assisted with the reducing agent NaBH4, followed by growing to complete gold shells in the presence of ascorbic acid (42.6% Au content). The properties of the composite particles including their chemical composition, morphology, particle size, size distribution, surface charge, magnetic responsiveness and photothermal ability were systematically characterized. The potential application of the γ-Fe2O3 @PMMA/CTS@Au hybrid particles in tumor diagnosis and therapy was assessed in vitro and in vivo using 4T1 tumor cells and 4T1 tumor-bearing mice through combining magnetic targeting, photoacoustic (PA)/computed tomography (CT) imaging and photothermal therapy. Results suggest that the γ-Fe2O3 @PMMA/CTS@Au particles can serve as a multifunctional tumor theranostic nanoplatform for magnetically targeted photothermal therapy. Breast cancer has been effectively eliminated without the use of any anticancer drugs or contrast agents. Therefore, this type of core-shell hybrid particles represents a new composite particle design for effective and safe tumor theranostics.

Green synthesis of carrier-free curcumin nanodrugs for light-activated breast cancer photodynamic therapy.

Photodynamic therapy (PDT) is a promising procedure for breast cancer therapy. Curcumin (Cur), a hydrophobic polyphenol derived from the spice turmeric, has been considered as a potential photosensitizer for PDT with evoked immune response, excellent safety, and low cost. However, the translation of curcumin in clinical cancer therapy suffers from an insufficient therapeutic dose in tumor tissues due to its poor solubility and low bioavailability. In this study, carrier-free curcumin nanodrugs (Cur NDs) were prepared without using any toxic solvents through a facile and green reprecipitation method. Cur NDs exhibited distinct optical properties, light-sensitive drug release behavior, resulting in increased reactive oxygen species (ROS) generation and PDT efficacy on breast cancer cells compared with free Cur. Furthermore, cell apoptosis during Cur-based PDT was concomitant with the activation of the ROS-mediated JNK/caspase-3 signaling pathway. Overall, our carrier-free Cur nanodrugs may be promising candidates for facilitating the efficacy and safety of PDT against breast cancer.

Tea Polyphenol-Functionalized Graphene/Chitosan as an Experimental Platform with Improved Mechanical Behavior and Bioactivity.

In this study, water-soluble, one-step highly reduced and functionalized graphene oxide was prepared via a facile, environment-friendly method by using tea polyphenol (TP), which acted as both reducing agent and stabilizer. The product obtained, that is, tea polyphenol-reduced graphene oxide (TPG), was used as a reinforcing building block for the modification of a mechanically weak chitosan (CS), TPG/CS. The morphology and physicochemical and mechanical properties of the composite were examined by various characterizations. The tensile strength and elastic modulus of CS were greatly improved by TPG, as compared to the findings for GO incorporation. Additionally, to our knowledge, this study is an in-depth analysis of the osteoblast functions of CS/TPG, including aspects such as cell cytotoxicity, proliferation, and expression of ossification genes, alkaline phosphatase (ALP), and Runt-related transcription factor (Runx2), which showed advantages in favorably modulating cellular activity. It was concluded that TPG/CS showed a higher elastic modulus, better hydrophilicity, and excellent biocompatibility than the pristine chitosan for promoting the proliferation and differentiation of osteoblasts, as well as for accelerating the expression of ALP and Runx2 (as shown by reverse transcription polymerase chain reaction (RT-PCR)). These results may provide new prospects for the use of TPG in the modification of biomaterials and for broadening the application of TPG in biological fields.

Biodegradable CSMA/PECA/Graphene Porous Hybrid Scaffold for Cartilage Tissue Engineering.

Owing to the limited repair capacity of articular cartilage, it is essential to develop tissue-engineered cartilage for patients suffering from joint disease and trauma. Herein, we prepared a novel hybrid scaffold composed of methacrylated chondroitin sulfate (CSMA), poly(ethylene glycol) methyl ether-ε-caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA was used as abbreviation for MPEG-PCL-AC) and graphene oxide (GO) and evaluated its potential application in cartilage tissue engineering. To mimic the natural extracellular matrix (ECM) of cartilage, the scaffold had an adequate pore size, porosity, swelling ability, compression modulus and conductivity. Cartilage cells contacted with the scaffold remained viable and showed growth potential. Furthermore, CSMA/PECA/GO scaffold was biocompatible and had a favorable degradation rate. In the cartilage tissue repair of rabbit, Micro-CT and histology observation showed the group of CSMA/PECA/GO scaffold with cellular supplementation had better chondrocyte morphology, integration, continuous subchondral bone, and much thicker newly formed cartilage compared with scaffold group and control group. Our results show that the CSMA/PECA/GO hybrid porous scaffold can be applied in articular cartilage tissue engineering and may have great potential to in other types of tissue engineering applications.

Combined cancer photothermal-chemotherapy based on doxorubicin/gold nanorod-loaded polymersomes.

Gold nanorods (GNRs) are well known in photothermal therapy based on near-infrared (NIR) laser absorption of the longitudinal plasmon band. Herein, we developed an effective stimulus system -- GNRs and doxorubicin co-loaded polymersomes (P-GNRs-DOX) -- to facilitate co-therapy of photothermal and chemotherapy. DOX can be triggered to release once the polymersomes are corrupted under local hyperthermic condition of GNRs induced by NIR laser irradiation. Also, the cytotoxicity of GNRs caused by the residual cetyltrimethylacmmonium bromide (CTAB) was reduced by shielding the polymersomes. The GNRs-loaded polymersomes (P-GNRs) can be efficiently taken up by the tumor cells. The distribution of the nanomaterial was imaged by IR-820 and quantitatively analyzed by ICP-AES. We studied the ablation of tumor cells in vitro and in vivo, and found that co-therapy offers significantly improved therapeutic efficacy (tumors were eliminated without regrowth.) compared with chemotherapy or photothermal therapy alone. By TUNEL immunofluorescent staining of tumors after NIR laser irradiation, we found that the co-therapy showed more apoptotic tumor cells than the other groups. Furthermore, the toxicity study by pathologic examination of the heart tissues demonstrated a lower systematic toxicity of P-GNRs-DOX than free DOX. Thus, the chemo-photothermal treatment based on polymersomes loaded with DOX and GNRs is a useful strategy for maximizing the therapeutic efficacy and minimizing the dosage-related side effects in the treatment of solid tumors.