264
A. S. Shinde et al.
limiting the passive targeting [25]. Thus attachment of target molecules at the surface
of nanoparticles helped to overcome the limitation, also known as active targeting.
The delivery system, when equipped with the ‘homing device,’ it guides the carrier
towards the intended targets, is capable of recognizing and binding to the complementary receptors present on the surface of the cancer cells [22]. The ligands may also help
in protecting the NPs from the enzymatic destruction increasing its effectiveness of
the treatment and reduces the toxic effect on healthy tissues. For example, Kumar et al.
synthesized functionalized gold nanoparticles (AuNPs) with PMI (p12), therapeutic
peptide, and targeted peptide, CRGDK for binding to receptor neuropilin-1 which
are overexpressed on cancer cells resulting in membrane receptor-mediated internalization [26]. In in vitro studies, after maximum binding interaction with the MDAMB-321 cell surface, there is an increased rate of the delivery of therapeutic p12
peptide inside targeted cells [26]. FDA approved antibodies such as rituximab, ipilimumab, and trastuzumab used for clinical treatments, are widely studied ligands due
to their high specificity and availability [27]. Dendrimer conjugated with antibody
binds exclusively to human prostate adenocarcinoma cells [28].
Apart from the merits, antibodies are found difficult to conjugate with the
NPs, resulting in shorter circulation time and thus expensive. Peptides have shown
promising alternate solutions due to their smaller, stable, simple, and more comfortable to produce. Nucleic acid base aptamers consist of advantages of both peptides
and antibodies, but on the other hand, they degrade quickly. Other small molecules
can also be used as ligands on the NPs, such as folic acid for folate receptors [29].
Such units are small, stable, and easy to produce. Unfortunately, ligand detection
for relevant substrates is challenging. Even with the proper binding of receptors and
ligands, binding incompatibility can limit therapeutic efficiency. Multiple ligands
with different charges can increase overall affinity for binding, but the limited
binding ability and capacity of receptors will govern the quality and quantity of
the binding. For instance, the overly strong coupling can reduce tumor penetration,
hinder selectivity, and lead to an overdose of carriers [30].
Active targeting directs the nano-carriers to a specific cell, tissue, or organ, which
remains at the site of disease for an extended period, thereby increasing the local
accumulation of NPs. In comparison, passive targeting depends on the natural distribution of nano-carrier and the EPR effect. Both of these targeting processes depends
on the location of initial drug delivery and blood circulation [31].
5 Controlled Drug Release
A flawless drug carrier should have the ability of controlled drug release along
with the nature of a high load of the drug. Early release of drugs in blood circulation can harm healthy tissues and can show severe side effects. The evolving field
of Nanotechnology can overcome these side effects with the use of nanomaterials
for drug delivery. Many researchers use biodegradable materials such as polymeric
A. S. Shinde et al.
limiting the passive targeting [25]. Thus attachment of target molecules at the surface
of nanoparticles helped to overcome the limitation, also known as active targeting.
The delivery system, when equipped with the ‘homing device,’ it guides the carrier
towards the intended targets, is capable of recognizing and binding to the complementary receptors present on the surface of the cancer cells [22]. The ligands may also help
in protecting the NPs from the enzymatic destruction increasing its effectiveness of
the treatment and reduces the toxic effect on healthy tissues. For example, Kumar et al.
synthesized functionalized gold nanoparticles (AuNPs) with PMI (p12), therapeutic
peptide, and targeted peptide, CRGDK for binding to receptor neuropilin-1 which
are overexpressed on cancer cells resulting in membrane receptor-mediated internalization [26]. In in vitro studies, after maximum binding interaction with the MDAMB-321 cell surface, there is an increased rate of the delivery of therapeutic p12
peptide inside targeted cells [26]. FDA approved antibodies such as rituximab, ipilimumab, and trastuzumab used for clinical treatments, are widely studied ligands due
to their high specificity and availability [27]. Dendrimer conjugated with antibody
binds exclusively to human prostate adenocarcinoma cells [28].
Apart from the merits, antibodies are found difficult to conjugate with the
NPs, resulting in shorter circulation time and thus expensive. Peptides have shown
promising alternate solutions due to their smaller, stable, simple, and more comfortable to produce. Nucleic acid base aptamers consist of advantages of both peptides
and antibodies, but on the other hand, they degrade quickly. Other small molecules
can also be used as ligands on the NPs, such as folic acid for folate receptors [29].
Such units are small, stable, and easy to produce. Unfortunately, ligand detection
for relevant substrates is challenging. Even with the proper binding of receptors and
ligands, binding incompatibility can limit therapeutic efficiency. Multiple ligands
with different charges can increase overall affinity for binding, but the limited
binding ability and capacity of receptors will govern the quality and quantity of
the binding. For instance, the overly strong coupling can reduce tumor penetration,
hinder selectivity, and lead to an overdose of carriers [30].
Active targeting directs the nano-carriers to a specific cell, tissue, or organ, which
remains at the site of disease for an extended period, thereby increasing the local
accumulation of NPs. In comparison, passive targeting depends on the natural distribution of nano-carrier and the EPR effect. Both of these targeting processes depends
on the location of initial drug delivery and blood circulation [31].
5 Controlled Drug Release
A flawless drug carrier should have the ability of controlled drug release along
with the nature of a high load of the drug. Early release of drugs in blood circulation can harm healthy tissues and can show severe side effects. The evolving field
of Nanotechnology can overcome these side effects with the use of nanomaterials
for drug delivery. Many researchers use biodegradable materials such as polymeric