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In this study, nanohybrid materials consisting of graphene oxide (GO), β‑cyclodextrin (CD) and poly(amido amine) dendrimer (DEN) were successfully prepared by covalent bonding. GO-CD and GO-CD-DEN were found to be potential nanocarriers for anticancer drugs including chemotherapeutics (doxorubicin (DOX), camptothecin (CPT)) and photosensitizer (protoporphyrin IX (PpIX)). GO-CD possessed 1.2 times higher DOX-loading capacity than GO due to inclusion of additional DOX to the CD. The drug loading on GO-CD-DEN increased in the order: DOX < PpIX < CPT. Enhanced cytotoxicity of DOX and CPT and also the photocytotoxicity of PpIX were observed when the drugs were loaded in GO-CD and GO-CD-DEN. Functionalization of GO with CD and CD-DEN increased the uptake in cancer cells, and both GO-CD and GO-CD-DEN nanohybrids remained in the cytoplasm and were not uptaken into the nucleus, as shown in the flow cytometry and high-content screening study., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We synthesized a dextrin (DEX)-conjugated graphene oxide (GO) nanocarrier (GO 100 -DEX) as a potential drug delivery system to respond to a tumor-associated stimulus, α-amylase, that has high permeability through the fenestrated endothelial barrier to the tumor site. At acidic pH and in the presence of α-amylase to simulate tumor conditions, GO 100 -DEX released a 1.5-fold higher amount of doxorubicin (DOX) than of GO 100 . Under the same conditions, the cytotoxic effects of GO 100 -DEX/DOX were 2-fold greater than those of free DOX and 2.9-fold greater than those of GO 100 /DOX. Employing an in vitro biomimetic microfluidic blood vessel model lined with human umbilical vein endothelial cells, we evaluated the tumor vasculature endothelial permeation of GO 100 -DEX and GO 100 using dextrans of 10 and 70kDa for comparison and as standards to validate the microfluidic blood vessel model. The results showed that the permeabilities of GO 100 -DEX and GO 100 were 4.3- and 4.9-fold greater than that of 70kDa dextran and 2.7- and 3.1-fold higher than that of 10kDa dextran, thus demonstrating the good permeability of the GO-based nanocarrier through the fenestrated endothelial barrier., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier., Experimental Approach: 3 H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3 H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF)., Results: In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state., Conclusion/implications: The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier., Competing Interests: The authors report no conflicts of interest in this work.

Their limited solubility and lack of tumor selectivity limit the clinical usefulness of photosensitizers. Various nanostructures have been evaluated as delivery agents for photosensitizers in an attempt to overcome these obstacles, but these have typically been limited by premature clearance by the reticuloendothelial system (RES) and non-specific interactions with normal cells that result from their hydrophobic surfaces. In this study, we report our attempt to circumvent these problems by applying a low molecular weight chitosan (25 kDa) coating to a poly(lactic-co-glycolic acid)-diiodinated boron dipyrromethene (PLGA-I2BODIPY) nanoparticle-photosensitizer construct. This chitosan coating increased the hydrophilicity and decreased the charge of PLGA-I2 BODIPY nanoparticle surfaces without changing their size (average diameter 147 nm) or morphology. In comparison to the uncoated controls, the coated nanoparticles reduced the burst release of I2BODIPY, increased its predominantly lysosomal cellular uptake, and enhanced its photocytotoxicity in 4T1 murine and MDA-MB-231 human breast cancer cells. PLGA-Chitosan-I2BODIPY nanoparticles also showed reduced serum protein adsorption and macrophage uptake compared to the uncoated controls. In 4T1 tumor-bearing mice, the PLGA-Chitosan-I2BODIPY nanoparticles exhibited better tumor-targeting selectivity and significantly reduced accumulation in RES tissues, including the lymph nodes, spleen and liver (by 10.2-, 2.1- and 1.3-fold, respectively), and in non-tumorous organs, such as the skin and eyes (by 22.7- and 4-fold, respectively). The PLGA-Chitosan-I2BODIPY and PLGA-I2BODIPY nanoparticles also showed increased anticancer efficacy compared to free I2BODIPY. These results suggest that the low molecular weight chitosan (25 kDa) is a promising nanoparticle "stealth coating" that improves tumor selectivity.

Graphene oxide (GO)-based nanocarriers have been frequently studied due to their high drug loading capacity. However, the unsatisfactory biocompatibility of these GO-based nanocarriers hampers their use in clinical settings. This review discusses how each of the physicochemical characteristics (e.g., size, surface area, surface properties, number of layers and particulate states) and surface coatings on GO affect its in vitro and in vivo nanotoxicity. We provide an overview on the effect of GO properties on interactions with cells such as red blood cells, macrophages and cell lines, and experimental organisms including rodents, rabbits and Zebrafish, offering some guidelines for development of safe GO-based nanocarriers. We conclude the paper by outlining the challenges involving GO-based formulations and future perspectives of this research in the biomedical field., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Circulation half-life has become one of the major design considerations in nanoparticle drug delivery systems. By taking cues for designing long circulating carriers from natural entities such as red blood cells (RBCs) has been explored for many years. Among all the cellular carriers including leukocytes, fibroblasts, islets, and hepatocytes, RBCs offer several distinctive features. The present review underlines a discussion on the applications of different RBC carriers (RBC mimics) which can evade the body's reticuloendothelial system overcoming many barriers such as size, shape, accelerated blood clearance, mechanical properties, control over particle characteristics, and surface chemistry. Bilayer membrane liposomes infusing phospholipids have long been synthesized to mimic bioconcave RBC carriers using the notion of stealth liposomes. This is not a comprehensive review; some illustrative examples are given on how they are currently obtained. A special attention is devoted to the RBC mimics from polymers, red cell membrane ghosts, and the red cell membrane enclosing polymeric cores as potential drug carriers. The present research reveals the achievement of RBC surface charge to accord with the immune system as a game of hide and seek in a much promising way in the light of its pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) causes considerable morbidity and mortality, particularly in the case of post-cardiac infarction or kidney transplantation; however, the site-specific accumulation of small molecule reno-protective agents for AKI has often proved ineffective due to dynamic fluid and solute excretion and non-selectivity, which impedes therapeutic efficacy. This article reviews the current status and future trajectories of renal nanomedicine research for AKI management from pharmacological and clinical perspectives, with a particular focus on appraising nanosized drug carrier (NDC) use for the delivery of reno-protective agents of different pharmacological classes and the effectiveness of NDCs in improving renal tissue targeting selectivity and efficacy of said agents. This review reveals the critical shift in the role of the small molecule reno-protective agents in AKI pharmacotherapy - from prophylaxis to treatment - when using NDCs for delivery to the kidney. We also highlight the need to identify the accumulation sites of NDCs carrying reno-protective agents in renal tissues during in vivo assessments and detail the less-explored pharmacological classes of reno-protective agents whose efficacies may be improved via NDC-based delivery. We conclude the paper by outlining the challenges and future perspectives of NDC-based reno-protective agent delivery for better clinical management of AKI. Nanosized drug carrier (NDC) – based targeting of small molecular reno-protective agents (SMRA) to kidneys with acute injury were increasingly attempted and reported effective in vivo. This review critically appraised such in vivo reports and (i) uncovered the advantageous transition in the role of SMRA in managing acute kidney injury (AKI) from prophylaxis-orientated to therapeutic orientated (outer ring) when they are delivered to the kidney by the NDCs; and (ii) highlights the less-explored pharmacological classes of SMRA (middle ring) whose efficacies may be improved via NDC-based renal drug delivery. (* outer ring : intended use of NDC-SMRA for AKI, middle ring : SMRA of various pharmacological classes integrated into NDCs and tested in vivo). [Display omitted] [ABSTRACT FROM AUTHOR]