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A. S. Shinde et al.
vitronectin) or factor H (complement inhibitor). This protects from the complement
attack. This method is used by some bacteria and cancer cells, which helps to escape
complement-mediating lysis [156].
Surface coating and derivatization with molecules that help to alter the recognition
and engulfment by the phagocytes is the technique that makes the NPs ‘invisible’
to the recognition tools of the immune cells. This ‘Trojan horse’ strategy helps
nanomedicine to escape uptake and destruction [157]. This invisibility of NPs fails
to recognize it as dangerous and thus do not induce the polymorphonuclear phagocytes (PMNs) and inflammation reactions. For example, polysialic acids (negatively
charged) is a capsule to some pathogenic bacteria (like Neisseria meningitidis)
escapes recognition by the immune system. It is similar to that of the host polysaccharides like those existing on integrins molecules. Therefore, this can be utilized
for the synthesis of nanomedicine to evade the immune defense system [158].
PEG is a block copolymer when used for the coating of the nanoparticles can
help to decrease the opsonin adsorption and recognition by immune cells. It also
significantly reduces the uptake and destruction by RES (in vitro and in vivo) along
with the other procedures to manage NPs size and shape [159]. However, PEGylated
liposomes act as T-cell-independent antigen (type II) and induce antibody-dependent
(IgM) rapid clearance of its second dose of circulation, known to be accelerated blood
clearance (ABC) phenomenon. This consequence lacks the therapeutic effect [160].
The rate of ABC phenomenon depends on the NPs size, shape, surface charge,
liposomal composition, PEG density, dosage, and the interval between administered doses. Thus, while giving attention to these criteria while synthesizing the
nanomedicine will help to avoid immune recognition and antibody responses. At the
same time, the host immunological integrity will be spared.
Dendrimers are micellar nanostructures, branched symmetric structure polymeric
macromolecules containing highly dense functional groups at their periphery. Significant applications of dendrimer nanocarriers hold promise to facilitate diagnostic
imaging, gene transfection, non-viral gene transfer, drug delivery, detection, and
therapeutics for cancer and other diseases [161]. With different surface modifications, glycodendrimers, have been designed with anti-viral or anti-microbial effect as
anti-infective ligands. For example, a polysulfonate G4 polyamidoamine (PAMAM)
dendrimer can block HIV-1 and HIV-2 activity in vitro [162]. The infection is
prevented by the mechanism related to structural entrapment of the virus with
help of the branched structure. The dendrimer-mediated anti-microbial activity may
be due to the involvement of immune-modulation. For instance, the subcutaneous
melanoma mice model, when administered with N-acetyl-glucosamine-coated G1
PAMAMs, decreases tumor growth, and thus the survival of mice in increased. These
results were accompanied along with the increased number of CD69+ cells in tumor
tissues and spleen. The upregulation of the IFN-g, IL-1 h, IL-2, and TNF-a was
also observed [163]. Such a phenomenon was indicated with the over-expression
of pro-inflammatory chemokines and cytokines, such as MIL-1 h, MIP-1a, IL-8,
IL-1 h, IL-6, and TNF-a induced in macrophages and human dendritic cells by
glucosamine-modified G3.5 PAMAMs [164]. Thus, many synthesized dendrimers
A. S. Shinde et al.
vitronectin) or factor H (complement inhibitor). This protects from the complement
attack. This method is used by some bacteria and cancer cells, which helps to escape
complement-mediating lysis [156].
Surface coating and derivatization with molecules that help to alter the recognition
and engulfment by the phagocytes is the technique that makes the NPs ‘invisible’
to the recognition tools of the immune cells. This ‘Trojan horse’ strategy helps
nanomedicine to escape uptake and destruction [157]. This invisibility of NPs fails
to recognize it as dangerous and thus do not induce the polymorphonuclear phagocytes (PMNs) and inflammation reactions. For example, polysialic acids (negatively
charged) is a capsule to some pathogenic bacteria (like Neisseria meningitidis)
escapes recognition by the immune system. It is similar to that of the host polysaccharides like those existing on integrins molecules. Therefore, this can be utilized
for the synthesis of nanomedicine to evade the immune defense system [158].
PEG is a block copolymer when used for the coating of the nanoparticles can
help to decrease the opsonin adsorption and recognition by immune cells. It also
significantly reduces the uptake and destruction by RES (in vitro and in vivo) along
with the other procedures to manage NPs size and shape [159]. However, PEGylated
liposomes act as T-cell-independent antigen (type II) and induce antibody-dependent
(IgM) rapid clearance of its second dose of circulation, known to be accelerated blood
clearance (ABC) phenomenon. This consequence lacks the therapeutic effect [160].
The rate of ABC phenomenon depends on the NPs size, shape, surface charge,
liposomal composition, PEG density, dosage, and the interval between administered doses. Thus, while giving attention to these criteria while synthesizing the
nanomedicine will help to avoid immune recognition and antibody responses. At the
same time, the host immunological integrity will be spared.
Dendrimers are micellar nanostructures, branched symmetric structure polymeric
macromolecules containing highly dense functional groups at their periphery. Significant applications of dendrimer nanocarriers hold promise to facilitate diagnostic
imaging, gene transfection, non-viral gene transfer, drug delivery, detection, and
therapeutics for cancer and other diseases [161]. With different surface modifications, glycodendrimers, have been designed with anti-viral or anti-microbial effect as
anti-infective ligands. For example, a polysulfonate G4 polyamidoamine (PAMAM)
dendrimer can block HIV-1 and HIV-2 activity in vitro [162]. The infection is
prevented by the mechanism related to structural entrapment of the virus with
help of the branched structure. The dendrimer-mediated anti-microbial activity may
be due to the involvement of immune-modulation. For instance, the subcutaneous
melanoma mice model, when administered with N-acetyl-glucosamine-coated G1
PAMAMs, decreases tumor growth, and thus the survival of mice in increased. These
results were accompanied along with the increased number of CD69+ cells in tumor
tissues and spleen. The upregulation of the IFN-g, IL-1 h, IL-2, and TNF-a was
also observed [163]. Such a phenomenon was indicated with the over-expression
of pro-inflammatory chemokines and cytokines, such as MIL-1 h, MIP-1a, IL-8,
IL-1 h, IL-6, and TNF-a induced in macrophages and human dendritic cells by
glucosamine-modified G3.5 PAMAMs [164]. Thus, many synthesized dendrimers