Nanomaterials: Versatile Drug Carriers for Nanomedicine
283
1. Immune-mediated rejection or destruction—to avoid nanomedicine as a
dangerous foreign entity, leading to initiate immune defense reaction and further
elimination of the drug.
2. Immunotoxicity—to make sure nanomedicine do not cause unwanted inflammatory or immune responses, that may induce damage to the body.
3. Immunosafety—to design nanomedicine so that it won’t interfere with the normal
immune responses.
Nanoparticulate drug delivery system, when inoculated, immune system provokes
a series of reactions to protect the body from possible harm. The immune system
may trigger various defense mechanisms such as platelet activation, production of
antibodies, and inflammation. These reactions may further cause pathological consequences such as thrombosis, hemolysis, hypersensitivity reactions, which may lead
to the elimination of the nanomedicine from the system [152]. The reactions occurred
may be either past complement activation or direct NPs interaction. Although, during
the synthesis of nanomedicines, the bioactive contaminates, if eliminated carefully
and biocompatible materials are used, then the danger of its destruction may be
reduced.
Reticuloendothelial system (RES) helps in the capture and engulfment of the
particulate material at the tissue level. This includes tissue leukocytes, macrophages,
dendritic cells, epithelial and endothelial cells present in different organs (e.g., liver
and spleen). Some studies have revealed that positively charged particles can voluntarily get attached to the surface of the phagocyte membrane (negatively charged)
and are frequently more cytotoxic than anionic and neutral ones, thus abundantly
internalized. The process of endocytosis can be receptor-independent or -dependent
according to the active functional characteristics present of the size, shape, and NP
surface. Such sub micrometric particles are engulfed mostly via a receptor-mediated
mechanism, by the professional phagocytes (like monocytes and macrophages).
Here, the particle surface characteristics act as a critical element to determine the
receptor-mediated uptake. For example, if the NPs are opsonized with the IgG or
C3ib (one among the activated fragment of complement system), it can be recognized by specific receptors for Fcγ or C3ib on the phagocyte membrane and internalized. At the same time, the adsorption of serum albumin can sharply decrease
the recognition and uptake of the particle [153, 154]. After the nanomedicine is
administered intravenously, its composition of the “bioshell” (preferred than that of
‘protein corona,’ as it is not entirely made up of proteins) that covers NPs is not an
easy task to determine. The bioshells differ with time because of the on/off rate of
blood molecules that are adsorbed on the surface of the NPs, time (prolonged incubation in 100% plasma results in more stable shell forms), temperature (feverish of
patients) and blood composition (like age, sex and disease dependent). This causes
NPs-blood interaction as more of a dynamic process, where bioshell influences the
NPs surface characteristics and its degradation [155]. Many soluble defense or scavenging molecules (clotting components, inflammation complement fragments, adhesion molecules, collectins, etc.) are get adsorbed on the surface of the NPs. Sometimes, NPs may be able to adsorb anti-inflammatory factors (such as albumin, serpins,
283
1. Immune-mediated rejection or destruction—to avoid nanomedicine as a
dangerous foreign entity, leading to initiate immune defense reaction and further
elimination of the drug.
2. Immunotoxicity—to make sure nanomedicine do not cause unwanted inflammatory or immune responses, that may induce damage to the body.
3. Immunosafety—to design nanomedicine so that it won’t interfere with the normal
immune responses.
Nanoparticulate drug delivery system, when inoculated, immune system provokes
a series of reactions to protect the body from possible harm. The immune system
may trigger various defense mechanisms such as platelet activation, production of
antibodies, and inflammation. These reactions may further cause pathological consequences such as thrombosis, hemolysis, hypersensitivity reactions, which may lead
to the elimination of the nanomedicine from the system [152]. The reactions occurred
may be either past complement activation or direct NPs interaction. Although, during
the synthesis of nanomedicines, the bioactive contaminates, if eliminated carefully
and biocompatible materials are used, then the danger of its destruction may be
reduced.
Reticuloendothelial system (RES) helps in the capture and engulfment of the
particulate material at the tissue level. This includes tissue leukocytes, macrophages,
dendritic cells, epithelial and endothelial cells present in different organs (e.g., liver
and spleen). Some studies have revealed that positively charged particles can voluntarily get attached to the surface of the phagocyte membrane (negatively charged)
and are frequently more cytotoxic than anionic and neutral ones, thus abundantly
internalized. The process of endocytosis can be receptor-independent or -dependent
according to the active functional characteristics present of the size, shape, and NP
surface. Such sub micrometric particles are engulfed mostly via a receptor-mediated
mechanism, by the professional phagocytes (like monocytes and macrophages).
Here, the particle surface characteristics act as a critical element to determine the
receptor-mediated uptake. For example, if the NPs are opsonized with the IgG or
C3ib (one among the activated fragment of complement system), it can be recognized by specific receptors for Fcγ or C3ib on the phagocyte membrane and internalized. At the same time, the adsorption of serum albumin can sharply decrease
the recognition and uptake of the particle [153, 154]. After the nanomedicine is
administered intravenously, its composition of the “bioshell” (preferred than that of
‘protein corona,’ as it is not entirely made up of proteins) that covers NPs is not an
easy task to determine. The bioshells differ with time because of the on/off rate of
blood molecules that are adsorbed on the surface of the NPs, time (prolonged incubation in 100% plasma results in more stable shell forms), temperature (feverish of
patients) and blood composition (like age, sex and disease dependent). This causes
NPs-blood interaction as more of a dynamic process, where bioshell influences the
NPs surface characteristics and its degradation [155]. Many soluble defense or scavenging molecules (clotting components, inflammation complement fragments, adhesion molecules, collectins, etc.) are get adsorbed on the surface of the NPs. Sometimes, NPs may be able to adsorb anti-inflammatory factors (such as albumin, serpins,