Bifunctional RAFT Agent Directed Preparation of Polymer/Graphene Oxide Composites.

Polymer/graphene oxide (GO) composites, which combine the physical properties of GO and the processability of polymers, are of increasing interest in a variety of applications ranging from conductive foams, sensors, to bioelectronics. However, the preparation of these composites through physical blending demands the polymers with functional groups that interact strongly with the GO. Here the design and synthesis of a new bifunctional reversible addition-fragmentation chain transfer (RAFT) agent are demonstrated, which allows the synthesis of polymers with predetermined molecular weights and low dispersibilities (Ð), while having functionalities at both polymer termini that allow strong binding to GO. To access polymers with diverse thermal and mechanical properties, acrylonitrile-styrene-acrylate (ASA) copolymers with different types of acrylates, both short and long side chains, are synthesized under the control of the bifunctional RAFT agent. Furthermore, the strong binding between GO and the synthesized polymers is verified and explored to prepare polymer/GO composites with diverse tensile strengths and conductivity in the range of semiconductors. Overall, this novel RAFT agent is expected to expand the utility of polymer/GO composites by providing well-defined polymers with tunable properties and strong binding with GO.

Depolymerization of Trityl End-Capped Poly(Ethyl Glyoxylate): Potential Applications in Smart Packaging.

The temperature-dependent depolymerization of self-immolative poly(ethyl glyoxylate) (PEtG) capped with triphenylmethyl (trityl) groups is studied and its potential application for smart packaging is explored. PEtGs with four different trityl end-caps are prepared and found to undergo depolymerization to volatile products from the solid state at different rates depending on temperature and the electron-donating substituents on the trityl aromatic rings. Through the incorporation of hydrophobic dyes including Nile red and IR-780, the depolymerization is visualized as a color change of the dye as it changes from a dispersed to aggregated state. The ability of this platform to provide information on thermal history through an easily readable signal makes it promising in smart packaging applications for sensitive products such a food and other cargo that is susceptible to degradation.

Poly(ethyl glyoxylate)-Poly(ethylene oxide) Nanoparticles: Stimuli-Responsive Drug Release via End-to-End Polyglyoxylate Depolymerization.

The ability to disrupt polymer assemblies in response to specific stimuli provides the potential to release drugs selectively at certain sites or conditions in vivo. However, most stimuli-responsive delivery systems require many stimuli-initiated events to release drugs. "Self-immolative polymers" offer the potential to provide amplified responses to stimuli as they undergo complete end-to-end depolymerization following the cleavage of a single end-cap. Herein, linker end-caps were developed to conjugate self-immolative poly(ethyl glyoxylate) (PEtG) with poly(ethylene oxide) (PEO) to form amphiphilic block copolymers. These copolymers were self-assembled to form nanoparticles in aqueous solution. Cleavage of the linker end-caps were triggered by a thiol reducing agent, UV light, H2O2, and combinations of these stimuli, resulting in nanoparticle disintegration. Low stimuli concentrations were effective in rapidly disrupting the nanoparticles. Nile red, doxorubin, and curcumin were encapsulated into the nanoparticles and were selectively released upon application of the appropriate stimulus. The ability to tune the stimuli-responsiveness simply by changing the linker end-cap makes this new platform highly attractive for applications in drug delivery.

[The development of cell-penetrating peptides in drug delivery system].

Cell membrane serves as the natural barrier. Cell-penetrating peptides(CPPs) have been a powerful vehicle for the intracellular delivery of a large variety of cargoes cross the cell membrane. The efficiency of intracellular delivery of drugs, proteins, peptides and nucleic acid, as well as various nanoparticulate pharmaceutical carriers(e.g., liposomes, polymeric micelles and inorganic nanoparticles) has been demonstrated both in vitro and in vivo. This review focuses on the CPPs-based strategy for intracellular delivery of small molecule drugs, proteins, peptides, nucleic acid and CPP-modified nanocarriers.

Antibacterial, antioxidant and fruit packaging ability of biochar-based silver nanoparticles-polyvinyl alcohol-chitosan composite film.

Silver nanoparticles were prepared by loading Ag+ into biochar of waste barley distillers' grains shell by reduction with trisodium citrate, and this silver-loaded biochar was introduced into polyvinyl alcohol-chitosan. Various analysis with Fourier Transform Infrared spectroscopy, X-ray diffraction, Thermogravimetric analysis, and water contact angle revealed that biochar-based silver nanoparticle was incorporated into the polyvinyl alcohol-chitosan film, the biochar-based silver nanoparticles-polyvinyl alcohol-chitosan (C-Ag-loaded PVA/CS) composite film had good thermostability and hydrophobicity. Through the analysis via disk diffusion method, the composite containing 3 % of biochar-based silver nanoparticles-polyvinyl alcohol-chitosan had high antibacterial activity (inhibition zone: 18 mm against E. coli and 15 mm against S. aureus), and the bacterial membrane permeability was measured, indicating that C-Ag-loaded PVA/CS composite film could destroy the cell membrane, release intracellular substances, and have high antioxidant activity. During the storage, the weight loss rate of the biochar-based silver nanoparticles-polyvinyl alcohol-chitosan plastic wrap group was 0.14 %, and the titratable acid content only decreased by 0.061 %, which had a good effect on extending the shelf life of blueberries. The C-Ag-loaded PVA/CS composite film could also delay deterioration of blueberries and prolong storage time. Overall, this composite film had potential in food packaging and extending food shelf-life aspects.

Combination of solid acid and solvent pretreatment for co-production of furfural, xylooligosaccharide and reducing sugars from Phyllostachys edulis.

The efficient utilization of biomass resources has gained widespread attention in current research. This study focused on the conversion of hemicellulose into xylo-oligosaccharides and furfural, as well as enhanced cellulose saccharification and lignin removal from residual biomass. The solid acid catalyst AT-Sn-MMT was prepared by sulfonation and tin ion loading of montmorillonite K-10. In a mixture of deep eutectic solvent and γ-valerolactone (3:7, v/v), AT-Sn-MMT was used to catalyze Phyllostachys edulis (PE) at 160 °C for 20 min, obtaining a furfural yield of 85.7 % and 1.5 g/L xylo-oligosaccharides. The delignification of pretreated PE was 59.5 %, reaching an accessibility of 221.3 g dye/g material. While the enzymatic saccharification efficiency was increased to 73.1 %. This work drew on the merits of solid acid catalysts and mixed solvent systems, and this constructed pretreatment method could be efficiently applied for co-production of reducing sugars, xylooligosaccharide and furfural, realizing the efficient valorization of PE.

UV-blocking, antibacterial, corrosion resistance, antioxidant, and fruit packaging ability of lignin-rich alkaline black liquor composite film.

The novel multifunctional active packaging composite film with antimicrobial, antioxidant, water-vapor and UV-barrier, and corrosion resistance properties was successfully prepared from waste biomass. In this study, waste poplar sawdust was pretreated using green liquor to extract black liquor (BL). BL was then mixed with polyvinyl alcohol (PVA) solution for synthesizing silver nanoparticles (AgNPs). PVA-BL-AgNPs film was fabricated by solution casting method, and the microstructure characterization and macroscopic performance testing of the composite film were conducted. The results revealed that PVA-BL-AgNPs film exhibited inhibitory effects against Staphylococcus aureus (inhibition zone: 33.6 mm), Pseudomonas aeruginosa (inhibition zone: 31.6 mm), and Escherichia coli (inhibition zone: 32.0 mm). It could eliminate over 99 % of 2,2-diazodi (3-ethyl-benzothiazol-6-sulfonic acid) (ABTS) free radicals and provided 100 % UV-blocking, reducing light-induced food damage. It exhibited the improvement of water-vapor barrier properties and corrosion resistance. In vitro cytotoxicity assays demonstrated that no significant impact occurred on cell proliferation, confirming the safety of the film. Packaging experiments showed that PVA-BL-AgNPs film effectively inhibited milk spoilage and prolonged the shelf-life of bread and bananas. Therefore, PVA-BL-AgNPs film might extend the shelf-life of food and offer significant opportunities in addressing the issues of low safety and environmental pollution associated with traditional packaging films.

Research progress on the application of magnesium phosphate bone cement in bone defect repair: A review.

BACKGROUND: Bone defects arising from diverse causes, such as traffic accidents, contemporary weapon usage, and bone-related disorders, present significant challenges in clinical treatment. Prolonged treatment cycles for bone defects can result in complications, impacting patients' overall quality of life. Efficient and timely repair of bone defects is thus a critical concern in clinical practice. OBJECTIVE: This study aims to assess the scientific progress and achievements of magnesium phosphate bone cement (MPC) as an artificial bone substitute material. Additionally, the research seeks to explore the future development path and clinical potential of MPC bone cement in addressing challenges associated with bone defects. METHODS: The study comprehensively reviews MPC's performance, encompassing e.g. mechanical properties, biocompatibility, porosity, adhesion and injectability. Various modifiers are also considered to broaden MPC's applications in bone tissue engineering, emphasizing drug-loading performance and antibacterial capabilities, which meet clinical diversification requirements. RESULTS: In comparison to alternatives such as autogenous bone transplantation, allograft, polymethyl methacrylate (PMMA), and calcium phosphate cement (CPC), MPC emerges as a promising solution for bone defects. It addresses limitations associated with these alternatives, such as immunological rejection and long-term harm to patients. MPC can control heat release during the curing process, exhibits superior mechanical strength, and has the capacity to stimulate new bone growth. CONCLUSION: MPC stands out as an artificial bone substitute with appropriate mechanical strength, rapid degradation, non-toxicity, and good biocompatibility, facilitating bone repair and regeneration. Modification agents can enhance its clinical versatility. Future research should delve into its mechanical properties and formulations, expanding clinical applications to create higher-performing and more medically valuable alternatives in bone defect repair.

[Research progress of new multifunctional bone cement in bone tumor therapy].

Objective: The research progress of new multifunctional bone cement in bone tumor therapy in recent years was reviewed, in order to provide help for the future research of anti-tumor bone cement. Methods: The related literature on the treatment of bone tumors with new multifunctional bone cement at home and abroad in recent years was extensively reviewed and summarized. Results: The new multifunctional bone cements include those with the functions of photothermotherapy, magnetic thermotherapy, chemoradiotherapy, and antibacterial after operation, which are discussed from the aspects of anti-tumor, drug controlled release, and cytotoxicity. Controlled drug release has been achieved in multifunctional bone cements by adjusting heat and pH or incorporating particles such as chitosan oligosaccharides and γ-cyclodextrin. At present, multifunctional bone cement with hyperthermia, radiotherapy, and chemotherapy has effectively inhibited the local recurrence and distant metastasis of bone tumors. Broadening the application of bone cement for photothermal and magnetic thermal therapy to deeper bone tumors, investigating more precise controlled release of drug-loaded bone cement, and introducing nanoparticles with both thermal conversion and intrinsic enzymatic activities into bone cement for synergistic anti-tumor therapy are promising research directions. Conclusion: The new multifunctional bone cement inhibits bone tumor cells, promotes new bone formation in bone defects, and prevents incision infection after tumor resection. Certain progress has been made in anti-tumor, antibacterial, drug-controlled release, and reduction of cytotoxicity. Expanding the deeper application range of the new multifunctional bone cement, verifying the safety in clinical application, and focusing on the individualized treatment of the new multifunctional bone cement are the problems that need to be solved in the future.

Ultraviolet blocking ability, antioxidant and antibacterial properties of newly prepared polyvinyl alcohol-nanocellulose­silver nanoparticles-ChunJian peel extract composite film.

In this work, nanocellulose (CNC) from waste water chestnut (WCT) shell was firstly used for preparing nanocomposite films, by using ChunJian peel extract (CJPE) as a green reducing agent to synthesize silver nanoparticles (AgNPs), and then loading them into polyvinyl alcohol-nanocellulose (PVA-CNC) matrix, a multifunctional nanocomposite material that could be used in food packaging was developed. The prepared films were tested for mechanical strength, barrier properties, thermal properties, antibacterial, antioxidant and biocompatibility through various characterizations. The PVA-CNC-AgNPs-CJPE film had good thermostability, mechanical strength, barrier properties, and biocompatibility. Compared with pure PVA film and PVA-CNC film, PVA-CNC-AgNPs-CJPE could shield over 95 % of the UVB (320-275 nm) spectrum and UVC (275-200 nm) spectrum and most of the UVA (400-320 nm). By disk diffusion analysis, the inhibition zones of PVA-CNC-AgNPs-CJPE film against E. coli, P. aeruginosa, S. aureus and E. faecalis were 22.3 mm, 25.0 mm, 22.0 mm and 19.3 mm, respectively. The milk antibacterial simulation test confirmed that PVA-CNC-AgNPs-CJPE film could effectively limit bacterial reproduction and prolong the shelf life of milk. PVA-CNC-AgNPs-CJPE film had excellent UV barrier properties, good antioxidant properties and high-efficiency antibacterial activity, which is expected to be widely used in sustainable nanocomposite food packaging.

[Progress in antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants].

Objective: To review antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants, so as to provide reference for subsequent research. Methods: The related research literature on antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants in recent years was reviewed, and the research progress was summarized based on different kinds of antibacterial substances and osteogenic active substances. Results: At present, the antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants includes: ① Combined coating strategy of antibiotics and osteogenic active substances. It is characterized in that antibiotics can be directly released around titanium-based implants, which can improve the bioavailability of drugs and reduce systemic toxicity. ② Combined coating strategy of antimicrobial peptides and osteogenic active substances. The antibacterial peptides have a wide antibacterial spectrum, and bacteria are not easy to produce drug resistance to them. ③ Combined coating strategy of inorganic antibacterial agent and osteogenic active substances. Metal ions or metal nanoparticles antibacterial agents have broad-spectrum antibacterial properties and various antibacterial mechanisms, but their high-dose application usually has cytotoxicity, so they are often combined with substances that osteogenic activity to reduce or eliminate cytotoxicity. In addition, inorganic coatings such as silicon nitride, calcium silicate, and graphene also have good antibacterial and osteogenic properties. ④ Combined coating strategy of metal organic frameworks/osteogenic active substances. The high specific surface area and porosity of metal organic frameworks can effectively package and transport antibacterial substances and bioactive molecules. ⑤ Combined coating strategy of organic substances/osteogenic active substancecs. Quaternary ammonium compounds, polyethylene glycol, N-haloamine, and other organic compounds have good antibacterial properties, and are often combined with hydroxyapatite and other substances that osteogenic activity. Conclusion: The factors that affect the antibacterial and osteogenesis properties of titanium-based implants mainly include the structure and types of antibacterial substances, the structure and types of osteogenesis substances, and the coating process. At present, there is a lack of clinical verification of various strategies for antibacterial/osteogenesis dual-functional surface modification of titanium-based implants. The optimal combination, ratio, dose-effect mechanism, and corresponding coating preparation process of antibacterial substances and bone-active substances are needed to be constantly studied and improved.

Improved biotransformation of lignin-valorized vanillin into vanillylamine in a sustainable bioreaction medium.

Lignin is a critical biopolymer for creating a large number of highly valuable biobased compounds. Vanillin, one of lignin-derived aromatics, can be used to synthesize vanillylamine that is a key fine chemical and pharmaceutical intermediate. To produce vanillylamine, a productive whole-cell-catalyzed biotransformation of vanillin was developed in deep eutectic solvent - surfactant - H2O media. One newly created recombinant E. coli 30CA cells expressing ω-transaminase and L-alanine dehydrogenase was employed to transform 50 mM and 60 mM vanillin into vanillylamine in the yield of 82.2% and 8.5% under 40 °C, respectively. The biotransamination efficiency was enhanced by introducing surfactant PEG-2000 (40 mM) and deep eutectic solvent ChCl:LA (5.0 wt%, pH 8.0), and the highest vanillylamine yield reached 90.0% from 60 mM vanillin. Building an effective bioprocess was utilized for transamination of lignin-derived vanillin to vanillylamine with newly created bacteria in an eco-friendly medium, which had potential application for valorization of lignin to value-added compounds.

(3-Chloro-2-hydroxypropyl) trimethylammonium chloride and polyethyleneimine co-modified pomelo peel cellulose-derived aerogel for remelt syrup decolorization in sugar refining.

The crucial need for quality refined sugar has led to the development of advanced adsorbents, with a focus on the decolorization of remelt syrup. In this study, (3-chloro-2-hydroxypropyl) trimethylammonium chloride and polyethyleneimine co-modified pomelo peel cellulose-derived aerogel (CP-PPA) was fabricated, and synthetic melanoidins were used as model colorants of remelt syrup to evaluate the validity and practicality of CP-PPA for eliminating colored impurities. Integrating abundant amine-functionalized groups (quaternary ammonium and protonated amine) within the pomelo peel-derived aerogel directionally captured electronegative melanoidins via electrostatic interactions. Furthermore, the active sites, types, and relative strength of the weak interactions between CP-PPA and melanoidins were determined using density functional theory simulations. CP-PPA exhibited an excellent equilibration adsorbing capacity for capturing melanoidins of 749.51 mg/g, and a removal efficiency of 93.69 %. Additionally, the adsorption mechanism was thoroughly examined in an effort to improve the economy of the sugar refinement industry.

Hyperbranched polyethyleneimine-functionalised chitosan aerogel for highly efficient removal of melanoidins from wastewater.

Melanoidins are hazardous dark-coloured substances contained in molasses-based distillery wastewater. Adsorption is an effective approach to eliminate melanoidins from wastewater. However, melanoidin adsorption capacities of available adsorbents are unsatisfactory, which seriously limits their practical application. A hyperbranched polyethyleneimine-functionalised chitosan aerogel (HPCA) was fabricated as an effective adsorbent for melanoidin scavenging. HPCA demonstrated superior melanoidin adsorption efficiency because of its high specific surface area, abundant amino functional groups, and high hydrophilicity. Melanoidin removal rate of HPCA was 94.95%, which remained at 91.45% after 5 cycles. Notably, using the Langmuir isothermal model, the maximum melanoidin adsorption capacity of HPCA was determined to be 868.36 mg/g, surpassing those of most of previously reported adsorbents. Toxicity experiments indicated that HPCA can be considered a safe adsorbent with excellent biocompatibility that hardly threatens aquatic organisms. The efficient melanoidin removal of HPCA was attributed to electrostatic attraction, H-bonding, and van der Waals force. However, the adsorption might be predominantly controlled by electrovalent interaction between protonated amino groups of HPCA and carboxyl/carboxylate groups of melanoidins. Two novel models, namely, external diffusion resistance-internal diffusion resistance mixed model and adsorption on active site model, were employed to describe the dynamic mass transfer characteristics of melanoidin adsorption by HPCA.

Efficient Valorization of Sugarcane Bagasse into Furfurylamine in Benign Deep Eutectic Solvent ChCl:Gly-Water.

Recently, highly efficient production of valuable furan-based chemicals from available and renewable lignocellulosic biomass has attracted more and more attention via a chemoenzymatic route in an environmentally friendly reaction system. In this work, the feasibility of chemoenzymatically catalyzing sugarcane bagasse into furfurylamine with heterogeneous catalyst and ω-transaminase biocatalyst was developed in the deep eutectic solvent (DES) ChCl:Gly-water. Sulfonated Al-Laubanite was firstly synthesized to catalyze sugarcane bagasse to furfural. SEM, BET, XRD, and FT-IR were used to characterize Al-Laubanite. Catalyst Al-Laubanite structure was significantly different from carrier laubanite. High furfural yield (60.9%) was achieved by catalyzing sugarcane bagasse in 20 min at 170 ℃ and pH 1.0 by Al-Laubanite (2.4 wt%) in the presence of ChCl:Gly (20 wt%). Potential catalytic mechanism was proposed under the optimized catalytic condition. In addition, one recombinant E. coli CV harboring ω-transaminase could completely transform biomass-derived furfural to furfurylamine at 40 °C and pH 7.5 using L-alanine as amine donor in ChCl:Gly-water (20:80, wt:wt). This established chemoenzymatic cascade reaction strategy was successfully utilized for valorization of biomass into furan-based chemicals in the benign ChCl:Gly-water system.

[Application and research progress of three-dimentional printed porous titanium alloy after tumor resection].

Objective: To review the current research and application progress of three-dimentional (3D) printed porous titanium alloy after tumor resection, and provide direction and reference for the follow-up clinical application and basic research of 3D printed porous titanium alloy. Methods: The related literature on research and application of 3D printed porous titanium alloy after tumor resection in recent years was reviewed from three aspects: performance of simple 3D printed porous titanium alloy, application analysis of simple 3D printed porous titanium alloy after tumor resection, and research progress of anti-tumor 3D printed porous titanium alloy. Results: 3D printing technology can adjust the pore parameters of porous titanium alloy, so that it has the same biomechanical properties as bone. Appropriate pore parameters are conducive to inducing bone growth, promoting the recovery of skeletal system and related functions, and improving the quality of life of patients after operation. Simple 3D printed porous titanium alloy can more accurately match the bone defect after tumor resection through preoperative personalized design, so that it can closely fit the surgical margin after tumor resection, and improve the accuracy and efficiency of the operation. The early and mid-term follow-up results show that its application reduces the postoperative complications such as implant loosening, subsidence, fracture and so on, and enhances the bone stability. The anti-tumor performance of 3D printed porous titanium alloy mainly includes coating and drug-loading treatment of pure 3D printed porous titanium alloy, and some progress has been made in the basic research stage. Conclusion: Simple 3D printed porous titanium alloy is suitable for patients with large and complex bone defects after tumor resection, and the anti-tumor effect of 3D printed porous titanium alloy can be achieved through coating and drug delivery.

Inflammation-targeting polymeric nanoparticles deliver sparfloxacin and tacrolimus for combating acute lung sepsis.

Sepsis is a complex disorder with very high morbidity and mortality; it can occur when an immune disorder triggers an invasion of pathogens in the host. Although many potential anti-infective and immunosuppressive treatments have been reported, we still do not have effective means of treating sepsis in clinic. The aim of this study is to develop a nanomaterial system that targets the site of inflammation and carries a combination of multiple drugs to better treat sepsis and alleviate its symptoms. We selected poly(lactide-co-glycolide acid) (PLGA) with good biocompatibility and degradability to prepare the nanoparticles (NPs) loaded with broad-spectrum antibiotic Sparfloxacin (SFX) and anti-inflammatory immunosuppressant Tacrolimus (TAC) by an emulsion-solvent evaporation method. The targeting ability of the NPs toward inflammatory sites is endowed by grafting of the γ3 peptide (NNQKIVNLKEKVAQLEA) that can specifically bind to the intercellular adhesion molecule-1 (ICAM-1), which is highly expressed on the surface of inflammatory endothelial cells. The drug loaded γ3-PLGA NPs have excellent cytocompatibility, low hemolysis ratio, and systemic toxicity. The drug loaded γ3-PLGA NPs also have excellent antibacterial property to both Gram-positive and Gram-negative bacteria and can effectively reduce the inflammation and immune response in acute lung infection mice. This study provides a simple and robust nanoplatform to treat lung infection induced sepsis, which may pave a way to design multifunctional nanomedicine for clinical translation.

Development of Fertilizer Coatings from Polyglyoxylate-Polyester Blends Responsive to Root-Driven pH Change.

Many current controlled-release fertilizers (CRFs) are coated with nonbiodegradable polymers that can contribute to microplastic pollution. Here, coatings of self-immolative poly(ethyl glyoxylate) (PEtG) capped with a carbamate and blended with polycaprolactone (PCL) or poly(l-lactic acid) (PLA) were evaluated. They were designed to depolymerize and release fertilizers in the vicinity of plant roots, where the pH is lower than that in the surrounding environment. PEtG/PCL coatings exhibited significant temperature and pH effects, requiring 18 days at pH 5 and 30 °C, compared to 77 days at pH 7 and 22 °C, to reach 15% mass loss. Plant roots were also effective in triggering coating degradation. Spray-coating and melt-coating were explored, with the latter being more effective in providing pellets that retained urea prior to polymer degradation. Finally, PEtG/PCL-coated pellets promoted plant growth to a similar degree or better than currently available CRFs.

A Dual-Modality MR/PA Imaging Contrast Agent Based on Ultrasmall Biopolymer Nanoparticles for Orthotopic Hepatocellular Carcinoma Imaging.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death and early stage diagnosis can greatly increase the survival rate of patient. However, the accurate detection of HCC remains an urgent challenge in medical diagnosis. The combination of magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) are conducive for accurate locating of cancerous tissue. Therefore, it is necessary to explore a more facile and biosafe dual-modal contrast agent for orthotopic HCC detection. METHODS: In this study, a promising contrast agent had been identified based on gadolinium chelated melanin nanoparticles and evaluated its usage as a dual-modal T1 MRI and PAI contrast agent for orthotopic HCC detection. RESULTS: The gadolinium-based melanin nanoparticles presented ultrasmall size, high chelation stability and negligible cytotoxicity estimated by CCK-8 assay. Moreover, the nanoparticle exhibited higher r1 relaxivity (45.762 mM-1 s-1) than clinically approved Gadodiamide (4.975 mM-1 s-1) at 1.5 T MR scanning. A linear regression analysis confirmed that the nanoparticles were ideal candidates for PAI in vitro. After the nanoparticles were injected into vein in mice with orthotopic HCC, a dramatic increase in signal of the liver was observed at 0.5 hr by MRI and PAI, while the tumor exerted remarkable signal enhancement at 7 hrs, showing excellent detection sensitivity. In addition, the nanoparticles exhibited excellent biocompatibility and they can be excreted through both hepatobiliary and renal pathways after diagnosis. CONCLUSION: These results indicate that the ultrasmall gadolinium chelated melanin nanoparticles is a promising candidate as a dual-modal MRI/PAI contrast agent for the detection of orthotopic HCC.

Ultrasmall endogenous biopolymer nanoparticles for magnetic resonance/photoacoustic dual-modal imaging-guided photothermal therapy.

Multi-modal imaging-guided photothermal therapy (PTT) has aroused extensive attention in biomedical research recently because it can provide more comprehensive information for accurate diagnosis and treatment. In this research, the manganese ion chelated endogenous biopolymer melanin nanoparticles were successfully prepared for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging-guided PTT. The obtained nanoparticles with an ultrasmall size of about 3.2 nm exhibited negligible cytotoxicity, high relaxivity for MRI, an excellent photothermal effect and PA activity. Moreover, in vivo MRI and PAI results all demonstrated that the nanoparticles began to diffuse in the blood after intratumoral injection into tumor-bearing mice and could spread throughout the whole tumor region at 3 h, indicating the optimal treatment time. The subsequent photothermal therapy of cancer cells in vivo was carried out and the result showed that tumor growth could be effectively inhibited without inducing any observed side effects. Besides, melanin as an endogenous biopolymer has native biocompatibility and biodegradability, and it can be excreted through both renal and hepatobiliary pathways after treatment. Therefore, the melanin-Mn nanoparticles may assist in better indicating the optimal treatment time, monitoring the therapeutic process and enhancing the therapeutic effect and showed great clinical translation potential for cancer diagnosis and therapy.