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Applications of Nanomedicine.

A Comprehensive Overview of the Development and Prospects of Nanobiotechnology in China.

Nanobiotechnology in the Republic of Korea.

Nanomedicine: Prospective Diagnostic and Therapeutic Potentials.

Nanotechnology: What it is and how it can be Applied in Healthcare.

The article starts of with an overview of the Institute of Bioengineering and Nanotechnology. It describes the focus of the institution. There are two research articles after the summary. One of it touches on non-cytotoxic and photostable quantum dots for bioimaing applications and the other is on silica-coated nanocomposites of magnetic nanoparticles and quantum dots.

This article is based on R&D strategy.

Aquatic pteridophyte (Azolla sp.) was taken to assess its potential to synthesize the metal (Au) nanoparticles. The synthesized particles were characterized using X-ray, UV-visible, scanning and transmission electron microscopy analyses. Nanoparticles almost spherical in shape having the sizes of 5–17nm are found. UV-visible study revealed the surface plasmon resonance at 538nm. Responsible phytochemicals for the transformation were principally phenolics, tannins, anthraquinone glycosides and sugars present abundantly in the plant thereby bestowing it adaptive prodigality. Also, the use of Azolla sp. for the synthesis of gold nanoparticles offers the benefit of eco-friendliness.

Nanomedicine is to apply and further develop nanotechnology to solve problems in medicine, i.e. to diagnose, treat and prevent diseases at the cellular and molecular level. This article demonstrates through a full spectrum of proof-of-concept research, from nanoparticle preparation and characterization, in vitro drug release and cytotoxicity, to in vivo pharmacokinetics and xenograft model, how nanoparticles of biodegradable polymers could provide an ideal solution for the problems encountered in the current regimen of chemotherapy. A system of vitamin E TPGS coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles is used as an example for paclitaxel formulation as a model drug. In vitro HT-29 cancer cell viability experiment demonstrated that the paclitaxel formulated in the nanoparticles could be 5.64 times more effective than Taxol^® after 24 hr of treatment. In vivo pharmacokinetics showed that the drug formulated in the nanoparticles could achieve 3.9 times higher therapeutic effects judged by area-under-the curve (AUC). One shot can realize sustainable chemotherapy of 168 hr compared with 22 hr for Taxol^® at a single 10 mg/kg dose. Xenograft tumor model further confirmed the advantages of the nanoparticle formulation versus Taxol^®.

Movement and shape changes are fundamental aspects of all living organisms. This biological motility results from the biological nanomotors, in particular protein nanomotors. Cells contain a variety of protein nanomotors that rotate (e.g., F₀F₁-ATP synthase or bacterial flagellar motors) or move in a linear fashion (e.g., the kinesin, myosin and dynein motors). F₀F₁-ATP synthase is one of the ideal nanomotors or energy providing systems for micro/nanomachines because of its small size, smart and perfect structure, and ultra-high energy transfer efficiency. Therefore, in this paper, we have reviewed the structure, mechanism, and potential applications of the F₀F₁-ATP synthase nanomotor. In all organisms, the F₀F₁-ATP synthase consists of two distinct nanomotors, F₀ and F₁. The F₀ moiety is embedded in the membrane and is a detergent soluble unit while the F₁ moiety protrudes from the membrane and is a water soluble unit. F₀F₁-ATP synthase operates as two stepper motor/generators coupled by a common shaft and an electrochemical-to-mechanical-to-chemical energy transducer with an astounding 360° rotary motion of subunits. F₀F₁-ATP synthase nanomotor may enable the creation of a new class of sensors, mechanical force transducers, actuators, and nanomechanical devices. Thus, the F₀F₁-ATP synthase nanomotor field has expanded into a wide variety of science.

Nanotechnology is one of the most important emerging fields of science in this century. It deals with designing, construction, investigation, and utilization of systems at the nanoscale. Another interesting research discipline of current day is biotechnology, which gives us a way to understand biological system and to utilize our knowledge for industrial manufacturing. Nanobiotechnology lies at the interface of these two research fields. It exploits nanotechnology and biotechnology to analyze and create nanobiosystems to meet a wide variety of challenges and develops a wide range of applications.

We report a novel method to simultaneously extract superoxide dismutase (SOD), catalase (CAT) and carbonic anhydrase (CA) from the same sample of red blood cells (RBCs). This avoids the need to use expensive commercial enzymes, thus allowing this to be cost effective for large-scale production of a nanobiotechnological polyHb-SOD-CAT-CA with enhancements to all three RBC functions. The best concentration of phosphate buffer for ethanol-chloroform treatment results in good recovery of CAT, SOD and CA after extraction. Different concentrations of the enzymes can be used to enhance the activity of polyHb-SOD-CAT-CA to 2, 4 or 6 times that of RBCs.

Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (poly-[Hb-SOD-CAT-CA]) contains all three major functions of red blood cells (RBCs) at an enhanced level. It transports oxygen, removes oxygen radicals and transports carbon dioxide. Our previous studies in a 90-minute 30 mm Hg MAP-sustained hemorrhagic shock rat model showed that it was more effective than blood in the lowering of elevated intracellular PCO₂, recovery of ST-elevation and histology of the heart and intestine. This paper analyzes the storage and temperature stability. The allowable storage time for RBCs is about 1 day at room temperature and 42 days at 4°C. Also, RBCs cannot be pasteurized to remove infective agents like HIV and Ebola. PolyHb can be heat sterilized and can be stored for a year even at room temperature. However, poly-[Hb-SOD-CAT-CA] contains both Hb and enzymes, and enzymes are particularly sensitive to storage and heat. We thus carried out studies to analyze its storage stability at different temperatures and heat pasteurization stability. The results of the storage stability show that lyophillization extends the storage time to a year at 4°C and 40 days at room temperature (compared to 42 days and 1 day, respectively, for RBCs). After the freeze-dry process, the enzyme activities of poly-[SFHb-SOD-CAT-CA] was 100 ± 2% for CA, 100 ± 2% for SOD, and 93 ± 3.5% for CAT. After heat pasteurization at 70°C for 2 hours, lyophilized poly-[Hb-SOD-CAT-CA] retained good enzyme activities of CA (97 ± 4%), SOD (100 ± 2.5%) and CAT (63.8 ± 4%). More CAT can be added during the crosslinking process to maintain the same enzyme ratio after heat pasteurization. Heat pasteurization is possible only for the lyophilized form of poly-[Hb-SOD-CAT-CA] and not for the solution. It can be easily reconstituted by dissolving it in suitable solutions that continue to have good storage stability (though less than that for the lyophilized form). According to the P50 value, poly-[SFHb-SOD-CAT-CA] retains its oxygen-carrying ability before and after long-term storage.

This study investigates the long-term effects of PEG-PLA nano-artificial cells containing hemoglobin (nanoRBCs) on renal function and renal histology after a one-third blood volume toploading in rats. The experimental rats received one of the following infusions: NanoRBCs in Ringer’s lactate solution, stroma-free hemoglobin (SFHb), polyhemoglobin (polyHb) or autologous rat whole blood (rat RBCs). Blood samples were taken before infusions and on Days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on Day 21 after the infusions and their kidneys were excised for histology examination. Infusion of SFHb induced significant decrease in renal function damage as evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in the SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed to be damaged. There was no abnormalities in renal biochemistry or histology in all the other groups (nanoRBCs, polyHb, Ringer’s lactate solution and rat RBCs). In conclusion, the injections of nanoRBCs did not have adverse effects on renal function or remal histology.

This study investigates the long-term effects of nano-dimension PEG-PLA artificial red blood cells (RBCs) containing hemoglobin and RBC enzymes on the liver and spleen after a one-third blood volume toploading in rats. The experimental rats received one of the following infusions: Nano-artificial RBCs in Ringer’s lactate solution, stroma-free hemoglobin, polyhemoglobin and autologous rat whole blood. Blood samples were taken before infusions and after infusions on Days 1, 7 and 21 for analysis. Nano-artificial RBCs, polyhemoglobin, Ringer’s lactate solution and rat RBCs did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand stroma-free hemoglobin induced significant adverse effects on the liver, as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On Day 21 after the infusions, rats were sacrificed and their livers and spleens were excised for histological examination. Nano-artificial RBCs, polyhemoglobin, Ringer’s lactate solution and rat RBCs did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in the rats’ central veins and sinusoids and hepatic steatosis. In conclusion, injected nano-artificial RBCs can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on livers or spleens.

Nanomedicine is to apply and further develop nanotechnology to solve problems in medicine, i.e. to diagnose, treat and prevent diseases at the cellular and molecular level. This article demonstrates through a full spectrum of proof-of-concept research, from nanoparticle preparation and characterization, in vitro drug release and cytotoxicity, to in vivo pharmacokinetics and xenograft model, how nanoparticles of biodegradable polymers could provide an ideal solution for the problems encountered in the current regimen of chemotherapy. A system of vitamin E TPGS coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles is used as an example for paclitaxel formulation as a model drug. In vitro HT-29 cancer cell viability experiment demonstrated that the paclitaxel formulated in the nanoparticles could be 5.64 times more effective than Taxol^® after 24 hr of treatment. In vivo pharmacokinetics showed that the drug formulated in the nanoparticles could achieve 3.9 times higher therapeutic effects judged by area-under-the curve (AUC). One shot can realize sustainable chemotherapy of 168 hr compared with 22 hr for Taxol^® at a single 10mg/kg dose. Xenograft tumor model further confirmed the advantages of the nanoparticle formulation versus Taxol^®.