Photothermal Research Articles

A Graphene-Based Lipid Modulation Nanoplatform for Synergetic Lipid Starvation/Chemo/Photothermal Therapy of Oral Squamous Cell Carcinoma.

Chemotherapy is one of the most commonly used treatments for oral squamous cell carcinoma (OSCC), but its use is limited by drug resistance and severe systemic toxicity. To eliminate these side effects and improve anti-tumor efficacy, several therapeutic approaches have been developed for use with chemotherapy. In this study, we developed a graphene-based lipid modulation nanoplatform (NSD) that carries SB-204990, a small molecule inhibitor specific for ATP citrate lyase (ACLY), and doxorubicin (DOX), a chemotherapeutic agent, and the trio enables synergistic treatment of OSCC with lipid starvation, chemotherapy, and photothermal therapy. We first determined whether ACLY expression was upregulated in OSCC, and then assessed the growth inhibitory effects of SB-204990 on SCC-15 cells and changes in lipid (acetyl coenzyme A, free fatty acids, and cholesterol) levels. We characterized NSD and then evaluated the stability, photothermal properties, drug loading, and release ability of NSD. Finally, the therapeutic effects of NSD on OSCC were investigated by in vitro and in vivo experiments, and the changes in lipid levels in OSCC tissues after ACLY inhibition were further evaluated. The results showed that ACLY was highly expressed in OSCC, and ACLY inhibition produced reproductive suppression and decreased lipid levels in SCC-15 cells. The NSD nanoplatform possessed good stability, photothermal properties, high drug loading capacity and controlled release. In addition, the triple therapy achieved satisfactory anticancer effects in both in vivo and in vitro assays, and the inhibition rate of tumors was as high as 99.4% in the NSD+Laser treatment group. The changes in tumor cell lipid levels and cell proliferation arrest induced by ACLY inhibition suggest that ACLY may be a promising target for lipid starvation therapy and resistance to chemoresistance, and its inhibitors are expected to become new anticancer drugs. The NSD nanocarrier system enables synergistic treatment with lipid starvation, chemotherapy, and photothermal therapy, which represents an innovative approach to combating tumors.

Au/Ag@ZnS yolk-shell photocatalysts enhanced with noble metals and hyaluronic acid for efficient hydrogen production in rheumatoid arthritis therapy

Rheumatoid arthritis, characterized by the abnormal proliferation of synovial cells and extensive macrophage infiltration, is a chronic inflammatory disease. Molecular hydrogen, known for its antioxidant properties, has shown promise in eliminating reactive oxygen species. However, the low solubility and bioavailability of hydrogen limit the effectiveness of this therapy. To overcome these issues, we developed a novel yolk-shell heterostructure, H-AAZS (Au/Ag@ZnS modified hyaluronic acid), utilizing a hydrothermal cation exchange process. Through ion doping, semiconductor hybridization, and Schottky barriers in H-AAZS, photocatalysis for hydrogen generation has been successfully implemented using 660 nm laser irradiation. Additionally, the H-AAZS demonstrate the capacity for mild photothermal therapy, inducing apoptosis in synovial cells with Au's hot electrons with 660 nm laser irradiation. This strategy not only improves the abnormal proliferation of synovial cells but also avoids the exacerbation of inflammation caused by thermal stimulation. Both in vitro and in vivo experiments validate the synergistic effects of hydrogen production mediated anti-inflammatory responses, macrophage polarization and photothermal therapy. Therefore, this work represents a significant advancement as it ingeniously harnesses photocatalysis to modulate the synovial microenvironment while mitigating the side effects associated with photothermal therapy. This nanocrystal provides new and valuable insights into the potential treatment of Rheumatoid arthritis.

Synergetic effect of Hexaferrite and reduced Graphene oxide (rGO) in Photothermal therapy and Hyperthermia applications

This research article describes the synthesis of composite materials by combining T-type hexagonal ferrite and reduced Graphene Oxide using the standard ceramic process. The Calcium-based T-type hexagonal ferrite was synthesized by using the sol-gel auto-combustion method whiles the reduced graphene oxide by adopting the Hummer method. The crystallite size varied in the range of 34.11 to 42.07nm as calculated from the X-ray diffraction (XRD) data. Consequently, the lattice parameters 'a' and 'c' decreased from 5.9 to 5.1Å and from 29.92 to 28.32Å, respectively. The use of atomic force microscopy (AFM) revealed a range of particle sizes at the surface, varying from 1.70nm to 3.85nm. Moreover, the saturation and remanence magnetization values demonstrated an increasing trend with T-type hexaferrites concentration whereas the coercivity decreased. The UV-vis near-infrared spectra exhibited substantial light absorption, characterized by a wide absorption range in the visible and near-infrared (NIR) region (700 to 1100nm) which indicates its use in Photothermal therapy (PTT). The Calcium T- type hexaferrite exhibited clear peaks in the blue, green, violet, and yellow spectra in its photoluminescence (PL) properties. These peaks are believed to be caused by oxygen vacancies and defects. The synthesized samples displayed a lossy behavior in the polarization-electric field (P-E) loop, with saturation polarization levels exceeding remnant polarization, which is an amenable condition for lossy behavior. Most importantly, the synthesized materials had significant thermal responses when exposed to an alternation (AC) magnetic field, indicating their potential use in magnetic hyperthermia applications.

Design of dinuclear osmium complex doped antifouling cellulose nanoparticles for targeting and dual photodynamic/photothermal therapy under near infrared irradiation

Transition metal-ligand has been explored in the treatment of tumors in photodynamic theray (PDT) or photothermal therapy (PTT) and Osmium complex attracts attentration due to its lower toxicity and longer absorption wavelength. However, there was no report about binuclear Os complex for combined therapy of PDT and PTT which could have a synergistic effect and improve the effectiveness. Herein, we synthesis of mono/dinuclear Os complexes (OsY1, OsY2) with dual PDT/PTT capabilities under a single near-infrared (NIR) excitation wavelength. These features arise from the large π-conjugated structure of our dinuclear Os complex coupled with efficient metal-to-ligand charge transfer, which bring in ultralow energy gaps of 0.733 eV and 0.308 eV for OsY1 and OsY2, respectively. Furthermore, we prepared the Osmium complex-doped, aptamer-conjugated cellulose NPs via the emulsion polymerization method. These NPs exhibit a notable ability to target mitochondria and posse a “protein corona-free” status, showing much higher efficiency in tumor ablation (76 %) than the commercialized indocyanine green (ICG) doped cellulose NPs (24 %) under 808 nm irradiation. Consequently, our designed mono/dinuclear Os complex, featuring a single-molecule dual PDT/PTT effect within doped antifouling NPs, holds promise for potential applications in cancer therapy.

Fe-based nanozyme with photothermal activity prepared from polymerization-induced self-assembly assays boosts the recovery of bacteria-infected wounds

Nowadays, the overuse of antibiotics has escalated bacterial infections into an increasingly severe global health threat. Developing non-antibiotic treatments has emerged as a promising strategy for treating bacterial infections. Notably, nanozyme-based composite materials have garnered growing interest. Therefore, the efficient preparation of nanozyme is important. Herein, we have presented an efficient method to prepare Fe-based nanozyme through polymerization-induced self-assembly assay to kill bacteria efficiently, which could significantly enhance the healing of infected wounds. Through polymerization-induced self-assembly assay, a large number of uniformly sized micelles, bearing imidazole groups, could be efficiently prepared. These nanoparticles subsequently chelate with Fe ions, followed by pyrolysis and etching processes, resulting in the production of uniformly small-sized nanozymes with high adsorption activity in the near-infrared region. The composite materials could effectively eradicate bacteria via a synergistic strategy of photothermal and catalytic therapies under infected microenvironments. In vivo animal models with full-thickness wounds showed that combination therapy not only eradicates 98 % of the bacteria but also significantly accelerates wound healing. This work underscores the utility of polymerization-induced self-assembly in the preparation of nanozymes and reveals promising applications of nanozymes in wound healing. Statement of significanceThis research introduces a functional nanozyme with photothermal activity, synthesized through polymerization-induced self-assembly, offering a promising non-antibiotic strategy to combat bacterial infections. This strategy enhances wound healing by combining photothermal and catalytic therapies, effectively eradicating drug-resistant bacteria while minimizing damage to healthy tissue. Our findings hold significant implications for the development of advanced antibacterial treatments and offer a robust assay to prepare nanozyme with small sizes. The prepared functional nanoparticles have a potential in wound healing, addressing a critical need in the face of rising antibiotic resistance.

Cu-S-Mo Interfacial Sites in CuO2@MoS2/PLLA Scaffolds for Robust Synergistic Antibacterial Efficacy via CDT and PTT

Bacterial infections considerably limit the success of scaffold transplantation. CuO2 may generate hydroxyl radicals through a self-cascade catalytic process, which is effective for sterilization. However, reducing CuO2-derived Cu+ ions to Cu° can lead to a decline in catalytic activity. To overcome these limitations, we anchored CuO2 onto MoS2 to establish stable Cu-S-Mo interfacial sites. The CuO2/MoS2 nanozyme was fabricated using a low-temperature co-precipitation technique and introduced into poly-L-lactic acid scaffolds using selective laser sintering. The Cu-S-Mo interfacial sites showed a triad of functions that synergistically enhanced catalytic performance. These sites stabilized the Cu atoms, augmented catalytic activity by facilitating efficient electron transfer through the Mo4+/Mo6+ redox couple, and improved the conduction of heat derived from the photothermal response of MoS2 to the Cu catalyst. The synergistic action of chemodynamic and photothermal therapy, mediated by the Cu-S-Mo sites, resulted in remarkable antibacterial efficacy, with 92.3% and 93.5% inhibition rates against Staphylococcus aureus and Escherichia coli, respectively. Experimental evidence and simulations demonstrated that Cu-S-Mo structure stabilized the Cu atoms and improved electron transfer via interatomic charge transfer. These results highlight the potential of the CuO2@MoS2/PLLA scaffold in eliminating bacterial infections.

Synthesis of heavy-atom-free thienoisoindigo dye as near-infrared photosensitizer for type I photodynamic therapy and photoacoustic imaging

Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-AD) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O2-•) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy.

Precise photothermal treatment of bacterial infection mediated by charge-switchable nanoplatform with acylsulfonamide betaine surface

Photothermal therapy (PTT) offers a promising approach for the treatment of drug-resistant bacterial-infected wounds, yet it requires precise targeting of thermal damage to bacteria rather than healthy tissues. Herein, ultrasmall CuS NPs modified with polyzwitterion containing acylsulfonamide betaine (PCBSA@CuS), which provides a sensitive and reversible charge conversion around pH 6.8, are used to enhance the healing of bacteria-infected wounds. In the acidic infection microenvironment, the majority of PCBSA@CuS can electrostatically adsorb onto bacterial cells through cationic exposure, resulting in direct damage and death of bacteria upon NIR irradiation. Additionally, the photothermal NPs rapidly return to a zwitterionic nature in normal physiological environments, ensuring lower affinity and avoiding thermal damage to healthy tissues during continuous PTT. Compared to inert photothermal systems such as PEG-modified CuS NPs, the NPs used in this study exhibited higher bactericidal and wound healing efficacy. Therefore, this nano-antibacterial agent with highly sensitive thermal-targeting function provides a novel photothermal strategy for efficient and biosafe treatment of infected wounds.

A novel nanomedicine integrating ferroptosis and photothermal therapy, well-suitable for PD-L1-mediated immune checkpoint blockade

A novel nanomedicine integrating ferroptosis and photothermal therapy, well-suitable for PD-L1-mediated immune checkpoint blockade

Metal-Phenolic Networks: A Promising Frontier in Cancer Theranostics.

The burgeoning field of cancer theranostics has been significantly advanced by the development of Metal-Phenolic Networks (MPNs), a new class of supramolecular architectures that integrate the advantages of metals and polyphenols. This review focuses on MPNs and their promising applications in cancer theranostics. Through a systematic literature search spanning from 2010 to 2023 in databases including PubMed, Scopus, and Web of Science. The period of search was justified by the rapid evolution of nanomaterials in cancer therapy, with MPNs emerging as a significant player in biomedical applications within the specified timeframe. This review discusses the classification and structure of polyphenolic compounds, as well as their mechanisms of action in cancer treatment. The applications of MPNs in chemotherapy drug delivery, photothermal therapy, chemodynamic therapy, biomedical imaging, and synergistic therapy are especially detailed. The authors emphasize the significance of MPNs in cancer nanomedicine and look forward to their future development directions.

Full-active pharmaceutical ingredient nanosensitizer for augmented photoimmunotherapy by synergistic mitochondria targeting and immunogenic death inducing.

The precise and effective activation of the immune response is crucial in promising therapy curing cancer. Photoimmunotherapy (PIT) is an emerging strategy for precise regulation and highly spatiotemporal selectivity. However, this approach faces a significant challenge due to the off-target effect and the immunosuppressive microenvironment. To address this challenge, a nanoscale full-active pharmaceutical ingredient (API) photo-immune stimulator was developed. This formulation overcomes the limitations of PIT by strengthening the ability to penetrate tumors deeply and inducing precise and potent mitochondria-targeted dual-mode photodynamic therapy and photothermal therapy. Along with inhibiting overexpressed Hsp90, this nanosensitizer in turn improves the immunosuppressive microenvironment. Ultimately, this mitochondria-targeted PIT demonstrated potent antitumor efficacy, achieving a remarkable inhibition rate of ≥95% for both established primary tumors and distant abscopal tumors. In conclusion, this novel self-delivery full-API nanosystem enhances the efficacy of phototherapy and reprograms the immunosuppressive microenvironment, thereby holding great promise in the development of precise and effective immunotherapy.

CaCO3-encircled hollow CuS nanovehicles to suppress cervical cancer through enhanced calcium overload-triggered mitochondria damage

Cervical cancer stands is a formidable malignancy that poses a significant threat to women's health. Calcium overload, a minimally invasive tumor treatment, aims to accumulate an excessive concentration of Ca2+ within mitochondria, triggering apoptosis. Copper sulfide (CuS) represents a photothermal mediator for tumor hyperthermia. However, relying solely on thermotherapy often proves insufficient in controlling tumor growth. Curcumin (CUR), an herbal compound with anti-cancer properties, inhibits the efflux of exogenous Ca2+ while promoting its excretion from the endoplasmic reticulum into the cytoplasm. To harness these therapeutic modalities, we have developed a nanoplatform that incorporates hollow CuS nanoparticles (NPs) adorned with multiple CaCO3 particles and internally loaded with CUR. This nanocomposite exhibits high uptake and easy escape from lysosomes, along with the degradation of surrounding CaCO3, provoking the generation of abundant exogenous Ca2+in situ, ultimately damaging the mitochondria of diseased cells. Impressively, under laser excitation, the CuS NPs demonstrate a photothermal effect that accelerates the degradation of CaCO3, synergistically enhancing the antitumor effect through photothermal therapy. Additionally, fluorescence imaging reveals the distribution of these nanovehicles in vivo, indicating their effective accumulation at the tumor site. This nanoplatform shows promising outcomes for tumor-targeting and the effective treatment in a murine model of cervical cancer, achieved through cascade enhancement of calcium overload-based dual therapy.

Lead-free perovskite Cs3Sb2Cl3I6 via additive engineering for enhancing output performance of optoelectronic and triboelectric coupled nanogenerator

Perovskite-based triboelectric nanogenerators (TENGs) are emerging as promising renewable energy devices that achieve optoelectronic and triboelectric coupling on their own to improve electric output. Nevertheless, the coupled electric output is susceptible to low triboelectric and optoelectronic properties due to internal defects of perovskites and limitations in film quality. Hence, in this work, additive engineering was used to introduce poly(ethylene oxide) (PEO) polymer into lead-free perovskite Cs3Sb2Cl3I6 precursor to modulate the crystal growth and passivate the crystal defects and optimize film quality, which can synergistically optimize optoelectronic and triboelectric properties. Under illumination, the open-circuit voltage (VOC) and the short circuit current (ISC) of unmodified Cs3Sb2Cl3I6-based TENG are 116V and 11.4 μA through optoelectronic and triboelectric coupling effects, respectively. In contrast, the VOC and ISC of TENG based on Cs3Sb2Cl3I6 modified by PEO are up to 184V and 19.1 μA, respectively, which increases by 58.62% and 67.54%. The maximum power density can reach 2.13Wm-2. Most importantly, the PEO-modified Cs3Sb2Cl3I6-based TENG exhibits excellent stability, which can maintain 90.9% of its initial triboelectric output within 40 days. This work declares that ligand modification is an effective strategy to improve the electric output of coupled TENG, providing a new perspective for achieving high-performance perovskite-based TENG, and photothermal therapy by monitoring both human motion and environmental light intensity.

NIR-induced antimicrobial efficacy of TPA-BOIMPY conjugate through photothermal and photodynamic synergy

Microbial infections, particularly those produced by multidrug-resistant bacteria, are a major risk to global wellness. In place of conventional antibiotics, photothermal therapy (PTT) and photodynamic therapy (PDT) use light-activated antimicrobial agents to transform near-infrared (NIR) light into heat and reactive oxygen species (ROS), respectively, which effectively eradicates pathogens. This study explored the potential of a new organic dye, bis-(borondifluoride)-8-imidazodipyrromethene (BOIMPY), as a NIR PTT/PDT agent. To increase its phototherapy characteristics, triphenylamines (TPA) were conjugated to BOIMPY to yield TPA-BOIMPY, and Pluronic F127 was utilized to improve the hydrophilicity of TPA-BOIMPY by forming TPA-BOIMPY@F127 nanoparticles with an average particle size of 79 nm. These nanoparticles exhibited an absorption peak at 757 nm, a photothermal conversion efficiency of 34 %, a singlet oxygen quantum yield of 0.02, and excellent photostability. Under 808 nm NIR irradiation, TPA-BOIMPY@F127 remarkably reduced the viability of both E. coli and S. aureus to 0.4 % and 7.3 %, respectively. The exceptional photostability and promising PTT/PDT capabilities of TPA-BOIMPY@F127 highlight its potential as a new class of NIR PTT/PDT agents for combating bacterial infections, contributing to the ongoing development of innovative therapeutic strategies.

Effect of hyaluronic acid on the formation of acellular dermal matrix-based interpenetrating network sponge scaffolds for accelerating diabetic wound healing through photothermal warm bath

Adequate vascularization essential for delivering nutrients critical to wound healing, yet impaired angiogenesis is a major barrier in diabetic wound repair. This study investigates the impact of hyaluronic acid on interpenetrating network sponge scaffolds derived from an acellular dermal matrix, with the aim of enhancing vascularization and healing of diabetic wounds via photothermal warm bath therapy. We prepared three-dimensional porous sponges (H1P4D2@DFO) using molecular interpenetration and ion crosslinking of porcine acellular dermal matrix (PADM), hyaluronic acid, and polydopamine nanoparticles loaded with deferoxamine mesylate (PDA@DFO). This resulting extracellular matrix-based sponge demonstrated properties suitable for wound repair, including high cell adhesion, biocompatibility, bioactivity, porosity (85 %), and water absorption (4500 %). The near-infrared (NIR) photothermal effect of PDA@DFO and the sustained release of deferoxamine mesylate (DFO) enhanced wound vascularization within the wound site. These findings suggest that our sponge scaffold can simulate skin-like structures and establish a supportive microenvironment conducive to microvascular reconstruction. By combining the photothermal warm bath approach with the scaffold's tailored 3D structure, we observed enhanced angiogenesis and accelerated diabetic wound healing, indicating potential clinical applications of these scaffolds in chronic wound management.

Chitosan-based hydrogels in cancer therapy: Drug and gene delivery, stimuli-responsive carriers, phototherapy and immunotherapy

Nanotechnology has transformed the oncology sector by particularly targeting cancer cells and enhancing the efficacy of conventional therapies. Environmentally friendly materials are the top choice for treating cancer. Chitosan, sourced from chitin, is widely used with its derivatives for the extensive synthesis or modification of nanoparticles. Chitosan has been deployed to develop hydrogels, as 3D polymeric networks capable of water absorption. The chitosan hydrogels are biocompatible and biodegradable structures that can deliver drugs, genes or a combination of them in cancer therapy. Increased tumor ablation, reducing off-targeting feature and protection of genes against degradation are benefits of using chitosan hydrogels in cancer therapy. The efficacy of cancer immunotherapy can be improved by chitosan hydrogels to prevent emergence of immune evasion. In addition, chitosan hydrogels facilitate photothermal and photodynamic therapy for tumor destruction. Chitosan hydrogels can synergistically integrate chemotherapy, immunotherapy, and phototherapy in cancer treatment. Additionally, chitosan hydrogels that respond to stimuli, specifically thermo-sensitive hydrogels, have been developed for inhibiting tumors.

Photo-Thermally Controllable Tumor Metabolic Modulation to Assist T Cell Activation for Boosting Immunotherapy.

Glycolysis is crucial for tumor cell proliferation, supporting their energy needs and influencing the tumor microenvironment (TME). On one hand, increased lactate levels produced by glycolysis acidifies the TME, inhibiting T cell activity. On the other hand, glycolysis promotes the expression of PD-L1 through various mechanisms, facilitating immune evasion. Therefore, controlled modulation of glycolysis in tumor cells to subsequently improve the immune tumor microenvironment holds significant implications for clinical cancer treatment and immune regulation. To reverse the immunosuppressive microenvironment caused by tumor glycolysis and reduce tumor immune escape, we developed a photo-thermal-controlled precision drug delivery platform to regulate tumor metabolism and aid in the activation of T cells, thereby enhancing immunotherapy. First, hollow mesoporous Prussian blue (HPB) was prepared, and the glycolysis inhibitor 3-bromopyruvate (3-BrPA) was encapsulated within HPB using the phase-change material 1-tetradecanol, resulting in B/T-H. This product was then modified with tumor cell membranes to obtain a photo-thermal controllable regulator (B/T-H@Membrane, B/T-HM). Due to the excellent drug loading and photo-thermal properties of HPB, upon reaching the tumor, B/T-HM can rapidly heat under 808 nm irradiation, causing the 1-tetradecanol to transition to a liquid phase and release 3-BrPA, which effectively inhibits tumor glycolysis through the HK2 pathway, thereby reducing tumor cell proliferation, decreasing lactate production, and downregulating tumor PD-L1 expression. In synergy with photo-thermal and αPD-1, this photo-thermally controllable metabolic-immune therapy effectively activates T cells to eliminate tumor. In response to the changes in immune microenvironment caused by tumor metabolism, a photo-thermal precision-controlled drug delivery platform was successfully developed. This platform reshapes the tumor immunosuppressive microenvironment, providing a new approach for T cell-based tumor immunotherapy. It also opens new avenues for photo-thermal controllable metabolic-immune therapy.

Biodegradable lipid bilayer-assisted indocyanine green J- aggregates for photothermal therapy: Formulation, in vitro toxicity and in vivo clearance

Biodegradable lipid bilayer-assisted indocyanine green J- aggregates for photothermal therapy: Formulation, in vitro toxicity and in vivo clearance

On-demand reprogramming of immunosuppressive microenvironment in tumor tissue via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immunotherapy using engineered gold nanoparticles for malignant tumor treatment

The frequent immune escape of tumor cells and fluctuating therapeutic efficiency vary with each individual are two critical issues for immunotherapy against malignant tumor. Herein, we fabricated an intelligent core-shell nanoparticle (SNAs@CCMR) to significantly inhibit the PD-1/PD-L1 mediated immune escape by on-demand regulation of various oncogenic microRNAs and perform RNAs dependent photothermal-immunotherapy to achieve precise and efficient treatment meeting the individual requirements of specific patients by in situ generation of customized tumor-associated antigens. The SNAs@CCMR consisted of antisense oligonucleotides grafted gold nanoparticles (SNAs) as core and TLR7 agonist imiquimod (R837) functionalized cancer cell membrane (CCM) as shell, in which the acid-labile Schiff base bond was used to connect the R837 and CCM. During therapy, the acid environment of tumor tissue cleaved the Schiff base to generate free R837 and SNAs@CCM. The SNAs@CCM further entered tumor cells via CCM mediated internalization, and then specifically hybridized with over-expressed miR-130a and miR-21, resulting in effective inhibition of the migration and PD-L1 expression of tumor cells to avoid their immune escape. Meanwhile, the RNAs capture also caused significant aggregation of SNAs, which immediately generated photothermal agents within tumor cells to perform highly selective photothermal therapy under NIR irradiation. These chain processes not only damaged the primary tumor, but also produced plenty of tumor-associated antigens, which matured the surrounding dendritic cells (DCs) and activated anti-tumor T cells along with the released R837, resulting in the enhanced immunotherapy with suppressive immune escape. Both in vivo and in vitro experiments demonstrated that our nanoparticles were able to inhibit primary tumor and its metastasis via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immune activations, which provided a promising strategy to reprogram the immunosuppressive microenvironment in tumor tissue for better malignant tumor therapy.

Construction of bilayer biomimetic periosteum based on SLA-3D printing for bone regeneration

An ideal biomimetic periosteum should have excellent biocompatibility to promote osteoclast adhesion and improve osseointegration, which is significant in promoting bone regeneration. In this work, a bionic artificial periosteum printed by the SLA-3D printing was prepared, consisting of a poly (ethylene glycol) diacrylate (PEGDA)/chitosan/tricalcium phosphate (TCP) fibrous layer and a gelatin methacryloyl (GelMA)/ammonium molybdate (Mo) cambium layer. Distinct surface characteristics were achieved on both sides of the biomimetic periosteum. Among them, the fibrous layer has high mechanical properties and low porosity, which is conducive to preventing the pulling of muscle tissues and the invasion of soft tissues. The cambium layer has a porous structure and bioactive factors that can effectively promote osteogenic differentiation of preosteoblasts. Combined with mild photothermal therapy triggered by NIR light, the biomimetic periosteum could promote bone regeneration at both the chemical and physical levels. This 3D-printed bilayer hydrogel can provide a promising strategy for preparing advanced tissue-engineered periosteum with excellent physical and bone regeneration properties.