Nanosponges are a type of nanoparticle, often a synthesized carbon-containing polymer. They are porous in structure, pores being about 1–2 nanometers in size, and can therefore be targeted to absorb small amounts of matter or toxin. Nanosponges are often used in medicine as targeted drug delivery systems, detoxification methods, or as a way of damage control after an injury. They can also be used in environmental applications to clean up ecosystems by performing tasks like purifying water or metal deposits. Their small size allows them to move quickly through substances, like water or blood, efficiently finding and attacking unwanted matter. Nanosponges are often synthetically manufactured but oftentimes include natural materials to improve their efficiency when injected into the body. Nanosponges are superior to microsponges in application as the smaller size allows less disruption into the system in which it is implemented therefore imposing less risk of failed or detrimental effects. The prefix "nano" implies that items of this size are measured on a scale of meters.
History Nanosponges were first referred to as "cyclodextrin nanosponges" by DeQuan Li and Min Ma in 1998. This term was used because there is a cross-linked β-cyclodextrin with organic diisocyanates. An insoluble network is present in this structure, which shows a high inclusion constant. These polymers are formed through the reaction of native cyclodextrins with a cross-linking agent, the latter influencing the behavior and properties of the entire unit.
Cyclodextrin nanosponges were not discovered to have potential in being drug carriers until work done by Trotta and colleagues. They performed syntheses of new kinds of cyclodextrin nanosponges that revealed many potential applications that had not been previously considered.
Mechanisms Structure
Cyclodextrins are a class of cyclic glucopyranose oligomers, with common structures of α, β, and γ. α-cyclodextrins comprise six glucopyranose units, β- cyclodextrins comprise seven, and γ comprise eight. Cyclodextrins are biological nanomaterials whose molecular structure greatly influences their supramolecular properties. To synthesize cyclodextrins, enzymatic action occurs on hydrolyzed starch.
Cyclodextrin nanosponges are made of a three dimensional cross-linked polymer network. They can be made with α, β, and γ cyclodextrins. The inclusion capacity and the solubilizing capacity of the nanosponges can be tuned according to how much of the cross-linking agent is used.
Functions Cyclodextrins have a toroidal shape, which allows them to have a cavity inside which can fit other molecules. This useful structure allows them to act as drug carriers in the body, as long as the compounds to be delivered have compatible geometry and polarity with the cavity. To determine when these compounds are delivered, the structure of the cyclodextrin nanosponge can be modified to release its contents sooner or later. Several ligands can be conjugated on the surface of the nanosponge to determine where it will target in the body.
Naturally inspired synthetic nanosponges
Liposomes When injected into the body, synthetic nanosponges made of liposomes can be coated with leukocytes. These leukocytes can be incorporated in nanoparticles though methods known as the "ghost-cell" or "hitchhiking" strategy. Hitchhiking strategy is when nanoparticles are trafficked by living leukocytes. The ghost cell method entails nanoparticles coated in the natural membrane. Since they are coated with leukocytes, the nanosponges will pull towards a location of infection or foreign matter in the body. The nanosponges avoid macrophage attack because they are coated with natural materials. Researchers have only tested these in lab animals but suggest the liposome nanosponge could be easier to get approved by the FDA for in-patient use. Researchers have found promising results in using these nanosponges in drug delivery, relieving inflammation, and repairing damaged tissue.
Coatings (RBC & RBC-PL) Common pathogens can be toxins that form pores in a cell membrane. These cells target red blood cells. When there are no red blood cells around, these toxins target platelets. Nanorobots with a coating similar to red blood cells and platelets exist, allowing them to be disguised as a red blood cell and/or platelet. These RBC-PL coated nanorobots display efficient propulsion in blood without apparent biofouling. Their movement mimics the movement of natural cells. This ability to blend in enhances their ability to bind to platelet-adhering pathogens. The increased binding ability helps the nanorobots more effectively neutralize toxins because a pathogen that targets these types of cells would be more likely to interact with the nanorobots. This, in turn, increases the amount of collisions and interactions between the nanorobots and the pathogens/toxins. The nanorobots help to absorb and remove the toxins and bacteria. Other functions of these nanorobots are the ability to neutralize cytolytic activity regardless of the molecular structure, enhancing mass transport, and they may also be able to fight auto-immune diseases. Having a natural coating on something synthetic allows the nanorobots to have the benefits of both natural and synthetic materials.
Environmental application
Oil pollution in the ground Substances like crude oil and tar pollute the ground and are difficult to clean up because of how they stick to dirt and soil. These toxic materials slipping into the soil can cause detrimental health effects to animals and people who consume plants grown in this soil. Current methods of trying to remove these pollutants from hazardous waste sites have proven to be costly and inefficient. Engineers at Cornell University have created a 20 nanometer long particle that can self assemble in water so that its orientation allows for a hydrophilic exterior and hydrophobic interior. These particles are small enough to travel quickly through sand and soil without getting trapped. The Cornell researchers injected these nanoparticles into the bottom of a steel column filled with sand contaminated by phenanthrene and a polycyclic aromatic hydrocarbon (PAH), components typically found in tar. They watched as the nanoparticles traveled up the column, cleaning the sand along the way. The hydrophobic cores of the nanosponge drew the phenanthrene off the sand grains and into the interior of the sponge.
Researchers intend to one day use this technology to improve upon "pump and treat remediation," in which polluted groundwater is pumped up to the surface, cleaned of its pollutants, and then injected back into the ground. With these nanoparticles implemented, pollutants can be more efficiently collected without getting trapped in the soil. Once cleaned of the toxins they have collected, they can be injected into the soil once more to continue cleaning.
Purification of wastewater Some nanosponges are made to be eco-friendly and have a high concentration of carboxyl groups. They are used to remove metal deposits in wastewater in the oceans, where organisms can absorb these deposits which leads to detrimental build up in their tissue. The concentration of heavy metals grows while going up the food chain as organisms eat other organisms. Being at the top of the food pyramid, humans are most at risk for the detrimental effects of these metals in our food. These effects include allergic reactions, insomnia, vision problems, and can be as extreme as to cause mental disability, dementia, and kidney disease. Unlike many organic pollutants, heavy metals can be removed and destroyed by using nanomaterials like nanosponges. These nanomaterials act as sustainable filtering materials by binding to metals and removing them from wastewater before they disperse into the ecosystem. Using nanosponges for this results in a higher efficiency and lower cost than alternative cleaning methods like ion exchange resins, activated carbon, or other biological agents. Porous materials produced from renewable and low cost sources, like cellulose, chitin, or starch, are one of the most promising classes of absorbents in terms of effectiveness.
Cyclodextrins (CDs) and amylose are derived from starches and are well known for their peculiar structural features and complex properties. The internal cavities in these CDs serve as sites for hydrophobic or very weakly hydrophilic molecules and hence generate a strong affinity to organic molecules at water-solid interfaces. In order to properly bind metal to these CDs, dextrins must be chemically changed by adding an acidic functional group. These functional groups are allowed to undergo deprotonation in an aqueous media so the reaction of these with the hydroxyl groups in dextrin allows negatively charged insoluble polymers to be created . These polymers are known as nanosponges for their porous characteristic; they are able to bond to both organic molecules and metal deposits. After cleaning, these nanosponges can easily be separated from the water through simple filtration since they are insoluble in all solvents.
One type of nanosponge being researched is prepared with β-cyclodextrins and a linear pea starch derivative called linecaps. β-cyclodextrins are used due to low cost and medium-sized pores allowing for a broad range of guest molecules to be collected. Additionally, β-cyclodextrins are favored over dextrin polymers, as they can interact with transition metals also. Primary and secondary hydroxyl groups can act as coordination sites with some metal ions, and CDs can coordinate more than one ion at a time. These two components are reacted with citric acid in water to create the nanosponges using sodium hypophosphate monohydrate as a catalyst for the reaction. These nanosponges were compared to the performance of nanosponges synthesized in the same manner substituting PDMA (pyromellitate substance) for citric acid.
A high number of cross-links were introduced into the synthesis process in order to create a maximum amount of carboxyl groups. This allowed for a higher complexation ability of these nanosponges to other molecules. A high degree of cross-linking generally leads to low swellable polymers which are more suited for water treatment, as the water will not take up the space meant for metal waste and can more easily be filtered from water after cleaning. Higher contact time leads to higher efficiency of the cleaning of nanosponges in wastewater.
It was found, at high metal concentrations, that pyromellitate was able to absorb more metal deposits. At low concentrations, they both performed nearly identical. However, in the presence of interfering sea water, citrate nanosponges were able to selectively absorb more metal than the PDMA nanosponges, allowing them to be more effective in the cleanup of metal from salt water. Although the research of these citric acid nanosponges is still undergoing revision and development, they show promise for being a sustainable way to clean metal deposits from the ecosystem.
Medical applications
Drug delivery Nanosponges are being researched to be used for drug delivery systems to treat cancer and infectious diseases. Although nanosponges are one three-thousandth the size of red blood cells, they each can carry thousands of drug molecules. They can hide in the immune system where immune cells try to destroy and remove foreign material from the body. Particles coated with membranes from circulating red blood cells cannot be detected. Additionally, particles coated with membranes from circulating white blood cells or leukocytes avoid attack from macrophages.