Superparamagnetic Nanocrystals Clustered Using Poly(ethylene glycol)-Crosslinked Amphiphilic Copolymers for the Diagnosis of Liver Cancer.

Superparamagnetic iron oxide (SPIO) nanocrystals have been extensively studied as theranostic nanoparticles to increase transverse (T2) relaxivity and enhance contrast in magnetic resonance imaging (MRI). To improve the blood circulation time and enhance the diagnostic sensitivity of MRI contrast agents, we developed an amphiphilic copolymer, PCPZL, to effectively encapsulate SPIO nanocrystals. PCPZL was synthesized by crosslinking a polyethylene glycol (PEG)-based homobifunctional linker with a hydrophobic star-like poly(ε-benzyloxycarbonyl-L-lysine) segment. Consequently, it could self-assemble into shell-crosslinked micelles with enhanced colloidal stability in bloodstream circulation. Notably, PCPZL could effectively load SPIO nanocrystals with a high loading capacity of 66.0 ± 0.9%, forming SPIO nanoclusters with a diameter of approximately 100 nm, a high cluster density, and an impressive T2 relaxivity value 5.5 times higher than that of Resovist®. In vivo MRI measurements highlighted the rapid accumulation and contrast effects of SPIO-loaded PCPZL micelles in the livers of both healthy mice and nude mice with an orthotopic hepatocellular carcinoma tumor model. Moreover, the magnetic micelles remarkably enhanced the relative MRI signal difference between the tumor and normal liver tissues. Overall, our findings demonstrate that PCPZL significantly improves the stability and magnetic properties of SPIO nanocrystals, making SPIO-loaded PCPZL micelles promising MRI contrast agents for diagnosing liver diseases and cancers.

Hollow Mesoporous Silica Nanoparticles for Dual Chemo-starvation Therapy of Hepatocellular Carcinoma.

PURPOSE: This study aims at chemotherapy and starvation therapy of HCC via starvation and apoptosis. METHODS: Hollow mesoporous organosilica nanoparticles (HMONs) with the thioether-hybrid structure were developed using an organic/inorganic co-templating assembly approach. Hydrofluoric acid was used to remove the internal MSN core for yielding large radial mesopores for loading drug cargos. The morphology and structure of NPs were determined using TEM and SEM. HMONs were stepwise surface modified with glucose oxidase (GOx), oxygen (O2) and Doxorubicin (DOX), and cancer cell membrane (CCM) for yielding CCM-coated HMONs (targeted stealth biorobots; TSBRs) for starvation, apoptotic, and enhanced cell uptake properties, respectively. The surface area and pore size distribution were determined via BET and BJH assays. The catalytic ability of GOx-modified NPs was measured using in vitro glucose conversion approach authenticated by H2O2 and pH determination assays. MTT assay was used to determine the cytotoxicities of NPs. Cell uptake and apoptotic assay were used for the NPs internalization and apoptosis mechanisms. The subcutaneous HepG2 tumor model was established in mice. The long-term in vivo toxicity was determined using blood assays. RESULTS: The prepared NPs were spherical, hollow and mesoporous with excellent surface area and pore size distribution. The GOx-modified NPs exhibited excellent catalytic activity. The TSBRs showed better cytotoxicity and reduce the tumor size and weight. The NPs showed long-term safety in vivo. CONCLUSION: TSBRs destroyed cancer cells by starvation and chemotherapy in both in-vitro and in-vivo settings which demonstrates its anti-cancer potential.

Biocontrol Microneedle Patch: A Promising Agent for Protecting Citrus Fruits from Postharvest Infection.

With increasing human awareness of food safety, the replacement of highly toxic pesticides with biocompatible antimicrobials has become a trend. This study proposes a biocontrol microneedle (BMN) to expand the application of the food-grade preservative epsilon-poly-L-lysine (ε-PL) in fruit preservatives by utilizing a dissolving microneedle system. The macromolecular polymer ε-PL not only possesses broad-spectrum antimicrobial activity but also exhibits good mechanical properties. With the addition of a small amount of polyvinyl alcohol, the mechanical strength of the ε-PL-based microneedle patch could be further improved to achieve an enhanced failure force of needles at 1.6 N/needle and induce an approximately 96% insertion rate in citrus fruit pericarps. An ex vivo insertion test revealed that the microneedle tips could be effectively inserted into the citrus fruit pericarp, rapidly dissolve within 3 min, and produce inconspicuous needle holes. Moreover, the high drug loading capacity of BMN was observed to reach approximately 1890 µg/patch, which is essential for enhancing the concentration-dependent antifungal activity of ε-PL. The drug distribution study has confirmed the feasibility of mediating the local diffusion of EPL in the pericarp through BMN. Therefore, BMN has great potential to reduce the incidence of invasive fungal infections in local areas of citrus fruit pericarp.

Poly(l-Ornithine)-Based Polymeric Micelles as pH-Responsive Macromolecular Anticancer Agents.

Anticancer peptides and polymers represent an emerging field of tumor treatment and can physically interact with tumor cells to address the problem of multidrug resistance. In the present study, poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF) block copolypeptides were prepared and evaluated as macromolecular anticancer agents. Amphiphilic PLO-b-PLF self-assembles into nanosized polymeric micelles in aqueous solution. Cationic PLO-b-PLF micelles interact steadily with the negatively charged surfaces of cancer cells via electrostatic interactions and kill the cancer cells via membrane lysis. To alleviate the cytotoxicity of PLO-b-PLF, 1,2-dicarboxylic-cyclohexene anhydride (DCA) was anchored to the side chains of PLO via an acid-labile ß-amide bond to fabricate PLO(DCA)-b-PLF. Anionic PLO(DCA)-b-PLF showed negligible hemolysis and cytotoxicity under neutral physiological conditions but recovered cytotoxicity (anticancer activity) upon charge reversal in the weakly acidic microenvironment of the tumor. PLO-based polypeptides might have potential applications in the emerging field of drug-free tumor treatment.

Nanostructured organic photosensitizer aggregates in disease phototheranostics.

Aggregate science provides promising opportunities for the discovery of novel disease phototheranostics. Under the guidance of aggregology and the Jablonski energy level diagram, photosensitizer aggregates with tunable photophysical properties can consequently result in tailorable diagnosis and treatment modalities. This review summarizes recent advances in the formation of nanostructured organic photosensitizer aggregates, their photophysical processes (e.g., radiative emission, vibrational relaxation, and intersystem crossing), and particularly, their applications in disease phototheranostics such as fluorescence imaging and sensing, photothermal therapy, photoacoustic imaging, and photodynamic therapy. It is expected that this comprehensive summary will provide guidance for the construction of nanostructured organic photosensitizer aggregates, for establishment of aggregation-photophysical property relationships and the development of novel disease phototheranostic nanomedicines.

A new approach based on CXCR4-targeted combination liposomes for the treatment of liver fibrosis.

Liver fibrosis results from excessive extracellular matrix accumulation due to injury and leads to cirrhosis, cancer, and death. Herein, we propose a chemokine receptor 4 (CXCR4)-targeted combination (CTC) liposomal therapy to treat carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model. This study aims to combine small molecules such as pirfenidone and AMD3100 in a single nanoplatform to investigate their synergistic antifibrotic effects in a setting of CCl4-induced liver fibrosis. CTC liposomes (CTC lipo) were prepared using the thin-film hydration method. CTC lipo exhibited a spherical shape, and the particle size was recorded at the nanoscale which confirms its appropriateness for in vitro and in vivo applications. CTC lipo had good storage and serum stability. The entrapped drugs in CTC lipo showed reduced toxicity at higher concentrations. CTC lipo displayed CXCR4 mediated cell uptake and were internalized by caveolae-mediated endocytosis. CTC lipo showed CXCR4 targeting and stromal cell-derived factor 1α (SDF1-α)/CXCR4 axis blocking activity. CTC lipo reduced the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and hydroxyproline (HYP) levels. The histological studies showed improved liver architecture and reduced collagen deposition after treatment. Transforming growth factor ß (TGFß), alpha-smooth muscle actin (α-SMA), and collagen I were elevated by CCl4 in comparison with the Sham. Upon CTC liposomal treatment, the quantitative score for the elevated fibrotic proteins such as TGFß, α-SMA, and collagen I was normalized. CTC lipo displayed significant downregulation of the upregulated TGFß, α-SMA, collagen I, and P-p38 expressions at the molecular level. The CXCR4 targeted liposomes showed prolonged biodistribution at 24 h. Our findings indicated that CTC lipo might be an alternative antifibrotic therapy that may offer new access to research and development. In a nutshell, the present study suggests that systemic administration of CTC lipo has efficient antifibrotic potential and deserves to be investigated for further clinical applications.

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Poly(l-ornithine)-Grafted Zinc Phthalocyanines as Dual-Functional Antimicrobial Agents with Intrinsic Membrane Damage and Photothermal Ablation Capacity.

Multifunctional antimicrobial peptides that combine the intrinsic microbicidal property of cationic polypeptide chains and additional antibacterial strategy hold promising applications for the treatment of infections caused by antibiotic-resistant bacteria, especially "superbugs". In the present study, star-shaped copolymers ZnPc-g-PLO with a zinc phthalocyanine (ZnPc) core and four poly(l-ornithine) (PLO) arms were designed, synthesized, and evaluated as dual-functional antimicrobial agents, that is, intrinsic membrane damage and photothermal ablation capacity. In an aqueous solution, amphiphilic ZnPc-g-PLO molecules self-assemble into nanosized polymeric micelles with an aggregated ZnPc core and star-shaped PLO periphery, where the ZnPc core exhibits appreciable aggregation-induced photothermal conversion efficiency. In the absence of laser irradiation, ZnPc-g-PLO micelles display potent and broad-spectrum antibacterial activities via physical bacterial membrane disruption as a result of the high cationic charge density of the star-shaped PLO. Upon laser irradiation, significant improvement in bactericidal potency was realized due to the efficacious photothermal sterilization from the ZnPc core. Notably, ZnPc-g-PLO micelles did not induce drug-resistance upon subinhibitory passages. In summary, dual-functional ZnPc-g-PLO copolymers can serve as promising antibacterial agents for the treatment of infectious diseases caused by antibiotic-resistant bacteria.

Cyclam-Modified Polyethyleneimine for Simultaneous TGFß siRNA Delivery and CXCR4 Inhibition for the Treatment of CCl4-Induced Liver Fibrosis.

BACKGROUND: Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death. PURPOSE: This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor ß (TGFß) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFß silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model. METHODS: Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFß silencing of PEI-Cyclam polyplex was authenticated by Western blotting. RESULTS: The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFß polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFß polyplex significantly downregulated α-smooth muscle actin, TGFß, and collagen type III. CONCLUSION: Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFß siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.

Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity.

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local "burst" release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6-6.3 µg mL-1), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.

Poly(α-l-lysine)-based nanomaterials for versatile biomedical applications: Current advances and perspectives.

Poly(α-l-lysine) (PLL) is a class of water-soluble, cationic biopolymer composed of α-l-lysine structural units. The previous decade witnessed tremendous progress in the synthesis and biomedical applications of PLL and its composites. PLL-based polymers and copolymers, till date, have been extensively explored in the contexts such as antibacterial agents, gene/drug/protein delivery systems, bio-sensing, bio-imaging, and tissue engineering. This review aims to summarize the recent advances in PLL-based nanomaterials in these biomedical fields over the last decade. The review first describes the synthesis of PLL and its derivatives, followed by the main text of their recent biomedical applications and translational studies. Finally, the challenges and perspectives of PLL-based nanomaterials in biomedical fields are addressed.

Unnatural Amino-Acid-Based Star-Shaped Poly(l-Ornithine)s as Emerging Long-Term and Biofilm-Disrupting Antimicrobial Peptides to Treat Pseudomonas aeruginosa-Infected Burn Wounds.

Peptide-based antimicrobial materials are recognized as promising alternatives to antibiotics to circumvent the emergence of antibiotic-resistant bacteria or to combat multiple resistant bacteria by targeting the bacterial cell membrane. The components and conformations of antimicrobial peptides are extensively explored to achieve broad-spectrum and effective antimicrobial activity. Here, star-shaped antimicrobial polypeptides are fabricated by employing homologs of poly(l-lysine)s (i.e., poly(l-ornithine)s, poly(l-lysine)s, and poly(l-α,ζ-diaminoheptylic acid)s) with the aim of modulating their charge/hydrophobicity balance and rationalizing their structure-antimicrobial property relationships. The in vitro antibacterial investigation reveals that unnatural amino-acid-based star-shaped poly(l-ornithine)s have remarkable proteolytic stability, excellent biofilm-disrupting capacity, and broad-spectrum antimicrobial activity, even against difficult-to-kill Gram-negative Pseudomonas aeruginosa. Furthermore, star-shaped poly(l-ornithine)s significantly reduce the microbial burden and improve the burn wound healing of mouse skin infected with P. aeruginosa. These results demonstrate that unnatural amino-acid-based star-shaped poly(l-ornithine)s can serve as emerging long-term and biofilm-disrupting antimicrobial agents to treat biofilm-related infections in burn, especially caused by notorious P. aeruginosa.

Calcium-cation-doped polydopamine-modified 2D black phosphorus nanosheets as a robust platform for sensitive and specific biomolecule sensing.

Many polymer decorated/modified 2D nanomaterials have been developed as enhanced drug delivery systems and photothermal theranostic nanoagents. However, few reports describe the use of these novel nanomaterials as nanoplatforms for biomolecule sensing. Herein, we used calcium-cation-doped polydopamine-modified (PDA-modified) 2D black phosphorus (BP) nanosheets (BP@PDA) as a sensing nanoplatform for the detection of nucleic acids and proteins in complex biological samples. Fluorescent-dye-labeled single-strand DNA aptamer/probes are adsorbed by the Ca2+-doped BP@PDA mediated by calcium-cation coordination. The PDA coating enhances the stability of the inner BP, provides binding sites to DNA nucleobases, and quenches fluorescence. Without any chemical conjugation, this sensing nanoplatform selectively and specifically detects protein (human thrombin, linear range: 10-25 nM, detection limit: 0.02 nM), single-strand DNA (linear range: 1-10 nM, detection limit: 0.52 nM) in 1% serum diluted samples, and senses intracellular mRNAs (C-myc, and actin) in living cells. The nanoplatform exhibits the advantages of both the 2D nanomaterial (BP) and the coating polymer (PDA), naturally enters living cells unaided by transfection agents, resists enzymatic lysis and shows high biocompatibility. This nanoplatform design contributes towards future biomolecule analytical method development based on polymer decorated/modified 2D nanomaterials.

Poly(L-Glutamic Acid)-Based Brush Copolymers: Fabrication, Self-assembly, and Evaluation as Efficient Nanocarriers for Cationic Protein Drug Delivery.

Protein drugs were considered to be the first choice to treat many human diseases, but their clinical application was usually limited by their short half-life and lack of validated targeted therapy. Here, a series of folate-functionalized poly(ethylene glycol)-b-(poly(2-aminoethyl-L-glutamate)-g-poly(L-glutamic acid))s (FA-PEG-b-(PELG-g-PLGA)s) were designed as tumor-targeted carriers for cationic protein delivery. Compared with traditional copolymers consisting of PEG and linear charged hydrophilic blocks, FA-PEG-b-(PELG-g-PLGA) with brush-like polyelectrolyte segments were beneficial to improving their electrostatic interactions with loading protein molecules, thus increasing drug-loading stability and protecting encapsulated proteins from degradation. The designed polymer brushes could efficiently encapsulate cytochrome C (CytC), a cationic model protein, to form polyion complex (PIC) micelles with an average particle size of approximately 200 nm. An in vitro drug release study showed that the drug-loading stability of the formed PIC micelles was largely improved. The functionalization of the block copolymer carriers with a targeting folate group enhanced the tumor cell growth inhibition and total apoptotic rates induced by CytC. Our results shed light on the unique advantages of brush-like polymer carriers in delivering cationic proteins, and the poly(L-glutamic acid)-based linear-brush diblock copolymers could be applied as a versatile delivery platform for molecular targeting in cancer therapy.

Poly(Ethylene Glycol) Crosslinked Multi-Armed Poly(l-Lysine) with Encapsulating Capacity and Antimicrobial Activity for the Potential Treatment of Infection-Involved Multifactorial Diseases.

With the development of modern medical technology, common diseases usually can be treated by traditional medicines and their formulation, while diseases with multiple etiologies still remain a great challenge in clinic. Nanoformulation was widely explored to address this problem. However, due to limited drug loading space of nanocarriers, co-delivery strategy usually fails to achieve sufficient loading of multiple drugs simultaneously. In this research, we explored the potential of poly(ethylene glycol) (PEG) crosslinked alternating copolymers MPLL-alt-PEG as both an anionic drug carrier and antimicrobial agent. The high cationic charge density of multi-armed poly(l-lysine) (MPLL) segments in MPLL-alt-PEG could endow the electrostatic encapsulation of anionic model drugs through the formation of polyion complex micelles with a MPLL/drug complex core and crosslinked PEG outer shell, enabling pH-sensitive drug release. Meanwhile, the MPLL-alt-PEG copolymer exhibits a broad spectrum of antimicrobial activities against various clinically relevant microorganisms with low hemolytic activity. Studies on antibacterial mechanism revealed that MPLL-alt-PEG attacked bacteria through the membrane disruption mechanism which is similar to that of typical antimicrobial peptides. Taken together, the present study shed light on the possibility of endowing a polymeric carrier with therapeutic effect and thus offered a promising strategy for achieving a comprehensive treatment of bacterial infection-involved multifactorial diseases.

Poly(ethylene glycol) crosslinked multi-armed poly(ε-benzyloxycarbonyl-L-lysine)s as super-amphiphiles: Synthesis, self-assembly, and evaluation as efficient delivery systems for poorly water-soluble drugs.

Polymeric micelles with high thermodynamic stability and loading capacity are of tremendous significance for their potential applications in drug delivery. In the present study, super-amphiphiles in the form of poly(ethylene glycol)-crosslinked multi-armed polyethylenimine-g-poly(ε-benzyloxycarbonyl-L-lysine)s (PEZ-alt-PEG) were designed, synthesized, and optimized as nanocarriers for hydrophobic drugs. In an aqueous solution, the copolymer PEZ-alt-PEG self-assembled into sub-100-nm spherical shell crosslinked micelles with low toxicity in vitro and in vivo. The crosslinked super-amphiphilic structure of PEZ-alt-PEG could not only enhance the thermodynamic stability of polymeric micelles, but it could also significantly improve the loading capacity of hydrophobic drugs, such as curcumin (CUR). CUR-loaded PEZ-alt-PEG micelles could mediate effective drug delivery with sustained and complete CUR release. The use of PEZ-alt-PEG micellar nanocarriers remarkably improved the cellular uptake of CUR and therefore exhibited effective inhibitory activity on the growth of human hepatoma (HepG2) cells. Compared to free CUR, CUR-loaded polymeric micelles significantly accelerated the apoptosis rate of HepG2 cells. Therefore, PEZ-alt-PEG polymeric micelles, with their high thermodynamic stability, high drug-loading capacity, enhanced drug uptake and improved pharmacodynamic effects, could serve as efficient and promising nanocarriers for poorly water-soluble drugs.

Proliferation and Migration of Lung Cancer Could be Inhibited by Oxymatrine through the Regulation for miR-520/VEGF.

Recent evidence suggests that Oxymatrine (OMT) has excellent effects in anticancer. The mechanism, however, remains unclear. In the present study, we investigated the potential mechanism of OMT against cancer. The differential expression of miRNA was screened by miRNA array. The expression of miRNA-520 and VEGF in lung cancer was assayed by real-time PCR, Western blot and immunohistochemistry, respectively. The direct interaction between miRNA-520 and VEGF was assayed by luciferase activity assay and their roles in lung cancer proliferation, invasion and migration were analyzed in vivo and in vitro. We found that miR-520 was markedly down-regulated and VEGF was markedly up-regulated in lung cancer tissues compared with adjacent normal tissues, which had significant negative correlation. Dual-luciferase assays confirmed that miR-520 directly targeting VEGF by binding to its upstream promoter region. Through in vitro and in vivo experiments, we found that different doses of OMT could up-regulate miR-520, selectively inhibit VEGF and thus inhibit the proliferation and migration of lung cancer. Our findings indicate that OMT inhibited cancer progression and metastasis by upregulation of miR-520 and downregulation of VEGF, which provide new support for OMT may be as a novel anticancer drug for the treatment of lung cancer in the future.

Phycocyanin/PEG-b-(PG-g-PEI) attenuated hepatic ischemia/reperfusion-induced pancreatic islet injury and enlarged islet functionality.

BACKGROUND: Hepatic ischemia/reperfusion-induced pancreatic islet injury (HI/RIPII) was an important pathophysiological phenomenon in clinics. In the present study, we observed the effects of phycocyanin on HI/RIPII. However, the half-life of phycocyanin was extremely short and limited its use in vivo. MATERIALS AND METHODS: In order to overcome this shortcoming, poly(ethylene glycol)-b-(poly(l-glutamic acid)-g-polyethylenimine) (PEG-b-(PG-g-PEI)) was synthesized and estimated as a nanocarrier for lengthening delivery of phycocyanin through the abdominal subcutaneous injection in rats. Phycocyanin (isoelectric point=4.3) was encapsulated with PEG-b-(PG-g-PEI) via electrostatic interactions at pH 7.4. RESULTS: In vitro phycocyanin was fast and efficiently encapsulated and showing efficient loading and sustained release. In vivo the anti-HI/RIPII function of phycocyanin/PEG-b-(PG-g-PEI) complex was surveyed in rats using free phycocyanin as the controls, and the results showed that phycocyanin/PEG-b-(PG-g-PEI) complex reduced HI/RIPII property and enlarged islet functionality. CONCLUSION: These results suggested that PEG-b-(PG-g-PEI) might be treated as a potential phycocyanin nanocarrier.

Gadolinium-conjugated star-block copolymer polylysine-modified polyethylenimine as high-performance T 1 MR imaging blood pool contrast agents.

Core-shell copolymers have received widespread attention because of their unique properties, such as suitable for surface modification and increasing the functionality. Thus, they have been increasingly used in many fields including biomedical, pharmaceutical, electronics and optics. Here, a new core-shell copolymer system was developed to synthesize potential blood pool contrast agent (CA) for magnetic resonance imaging (MRI). The novel CA with high T 1 relaxivity was synthesized by conjugating gadolinium (Gd) chelators onto star-block copolymer polyethylenimine-grafted poly(l-lysine) (PEI-PLL) nanoparticles (NPs). The T 1 relaxivity of PEI-PLL-DTPA-Gd NPs measured on a 7.0 T small animal MRI scanner was 8.289 mM-1 s-1, higher than that of T 1 contrast agents widely used in the clinic, such as Gd-DTPA (also known as Magnevist, r 1 = 4.273 mM-1 s-1). These results show that PEI-PLL-DTPA-Gd exhibits more efficient T 1 MR contrast enhancement compared to Gd-DTPA. More importantly, the PEI-PLL-DTPA-Gd core-shell NPs exhibited extremely low toxicity when measured against the HepG2 cell line over a similar concentration rang of Magnevist. In in vivo experiments, PEI-PLL-DTPA-Gd not only displayed good T 1 contrast enhancement for the abdominal aorta, but also showed prolonged blood circulation time compared with Gd-DTPA, which should enable longer acquisition time, for MR and MR angiographic images, with high resolution in clinical practice. PEI-PLL-DTPA-Gd NPs have potential to serve as high T 1 relaxivity blood pool MRI CA in the clinic.