PARAMETERS OF INTEREST

Although Type 1 diabetes has always been considered an irreversible autoimmune disease, some cell types, like Treg, are able to restore immune tolerance and suppression of the disease development. Liposomes targeted towards Treg cells have successfully been used to release therapeutic levels of immunomodulators, improving the autoimmune response.

Controlled release intends to deliver the therapeutic compound in the chosen region and in the required period. Both the release rate and where it takes place can be controlled.

Stimuli-responsive systems

Stimuli-responsive systems are able to control drug biodistribution in response to specific stimuli, either those found in the local environment of the target place (changes in pH, enzyme concentration or redox gradients) and those that are triggered by an external physical stimulus such as heat, ultrasound or light.

pH sensitive: Acidification of the nanocarrier environment triggers the release of its contents. It has been shown to be a great technique to target cancer cells since they have lower pH values than normal. Additionally, it can specifically reach organelles inside the cell like endosomes or lysosomes which pH is more acidic.

Enzyme-responsive: The destabilization of the nanocapsule membrane in the presence of a certain enzyme therefore releasing the cargo helps in accurately drug delivery. Enzymes that are overexpressed in the target tissue are great triggers for enzyme-responsive nanocarriers. Some examples could be phospholipase, matrix metalloproteinases, urokinase plasminogen activator, and many others that are involved in inflammatory and cardiovascular diseases as well as different cancers.

Redox responsive: The higher concentration inside cancer cells of glutathione generates a redox gradient that can be used to trigger the release of pharmaceuticals in its destiny.

Thermal sensitive liposomes: This strategy is especially useful when drug delivery is used in combination with local hyperthermia for cancer treatments. This way, when the heat treatment starts, the pharmaceutical is released which results in superior targeting and treatment efficiency.

Nanocarriers have enabled the controlled release of many compounds which are instable or cannot enter the cells on their own. However, their use in vivo is hindered by the interference from blood cells which prevent the release of the carried compound in the target tissue.
Modification of nanovesicles and nanoparticles surfaces with polymers and biomaterials, among others, provides nanosystems with increased steric stability and resistance. Additionally, it allows in vivo delivery strategies like long-circulating particles/vesicles or resistance to gastric conditions for intestinal release. Although there are many possibilities regarding nanoparticle or nanovesicle coatings, excellent examples are chitosan and PEG.

Other hydrophilic or glycolipids

Other hydrophilic polymers or glycolipids like PEG or GM1 help in removing unwanted interactions. Those have a flexible chain that occupy the space immediately adjacent to the nanovesicle or nanoparticle surface. As a consequence, it excludes other macromolecules from this space. Blood plasma opsonins cannot bind anymore to the nanocarrier, thus avoiding macrophage unspecific interactions.

Biomedical imaging as well as cell tracking play a key role in understanding structural as well as functional biological systems. However useful, traditional methods like bioluminescence and fluorescence imaging present some challenges that can be overcome with the use of nanotechnology.

Liposomes and polymeric nanovesicles, are of great interest due to their capacity to deliver a specific drug to its target while monitoring and tracking the location of the nanosystem in real time, and in vivo. This holds great potential to study the distribution as well as the bioaccumulation of the drug which is an indicator of efficiency and possible toxicity.

Additionally, a great variety of nanoparticles have already been developed and even used in clinical trials up to phase 4 for in vivo imaging, including spions, silver nanoparticles and CdS/ZnS quantum dots.

While this technology has been used to enhance different imaging modalities, it stands out in the case of magnetic resonance imaging as excellent contrasting agents. Nanoparticle cell tracking has also been reported with Magnetic Particle Imaging (MPI), fluorescence imaging, nuclear and photoacoustic imaging.

Additionally, nanoparticles can be multi-functional, allowing for different imaging methods to be used simultaneously and enabling more information to be obtained. Further functionalization can also help distinguish subtypes of tissues as in the case of tumors.