Application of Nanotechnology in Diagnosis and Therapeutics
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nanorods synthesized by self-assembly of amphiphilic dendritic polymer-drug conjugate showed greater circulation with longer blood clearance kinetics, high-cellular
uptake as well as higher accumulation (Arnida et al. 2011; Zhou et al. 2013). There
are also evidences indicating cylindrical-shaped NPs in contributing to higher circulation times and accumulation in the targeted tissue. For instance, in one of the
published study cylindrical silica NPs were found to get deposited in the liver than
the discoidal silica particles. Similarly amine-modified mesoporous silica nanorods
displayed predominant accumulation in the lungs that the equivalent nanospheres
(Dalhaimer et al. 2003, 2004; Geng et al. 2007).
2.3 Effect of Surface Charge
Zeta potential (ZP) is a scientific term for electrokinetic potential that expresses the
potential difference between the dispersion medium and fluid that is sticking over
the surface of the dispersed particles in the colloidal suspension (Kutscher et al.
2010). This is basically measured by two techniques: microelectrophoresis, which is
based on capturing the images of particles moving around, and the other one is electrophoretic light scattering, that is, based on dynamic light scattering (Kedar et al.
2010; Van Butsele et al. 2009). As discussed in the earlier sections, size and shape
of the NPs play a critical role in drug delivery. However, it has been observed that
negatively charged particles get easily opsonized and cleared by reticuloendothelial
system, mainly mediated by liver and spleen. Thus, variation in the surface charge
of the NPs can potentially aid in binding to the tissues (Chen et al. 2010; Patil et al.
2007; Reis et al. 2006). Cellular surfaces are rich in negatively charged proteoglycans that play a part in cellular proliferation, migration, and motility. Thus, NPs with
higher positive surface charge could show enhanced uptake by the cell. A study conducted by Patil et al. showed enhanced uptake of cerium oxide NPs, which had ZP of
−43 mV (Bernfield et al. 1999; Mislick and Baldeschwieler 1996). Whereas particles with less negative or positive charge did not show efficient uptake by the cells.
The uptake was highly pronounced due to electrostatic interactions. Interestingly, in
another study it was observed that NPs with lesser surface charge also showed uptake
by adsorption of negatively charged molecules on the cationic sites in the form of clusters. However, surface modification of NPs can alter the behavior of cellular uptake,
as in case of histidine substituted amino group of glycol chitosan self-assembled NPs.
Due to strong cationic nature of histidine at acidic pH, it is capable of interacting with
the endosomal membrane and its destabilization. Accordingly, the delivery of drugs
becomes convenient in case of cancer cells as well. Cancer cell surfaces are usually
negatively charged and acid-outside plasma pH gradients. This mediates stronger
interactions between cationic NPs and tumor tissues responsible for increased tumor
accumulation. This strategy is known as passive targeting or enhanced permeability
retention effect (EPR), where particle size along with the surface charge and stability
of the particles are known to contribute to the tumor accumulation (Park 2006; Staples et al. 2006). In similar to drug delivery through parenteral route, drug delivery
419
nanorods synthesized by self-assembly of amphiphilic dendritic polymer-drug conjugate showed greater circulation with longer blood clearance kinetics, high-cellular
uptake as well as higher accumulation (Arnida et al. 2011; Zhou et al. 2013). There
are also evidences indicating cylindrical-shaped NPs in contributing to higher circulation times and accumulation in the targeted tissue. For instance, in one of the
published study cylindrical silica NPs were found to get deposited in the liver than
the discoidal silica particles. Similarly amine-modified mesoporous silica nanorods
displayed predominant accumulation in the lungs that the equivalent nanospheres
(Dalhaimer et al. 2003, 2004; Geng et al. 2007).
2.3 Effect of Surface Charge
Zeta potential (ZP) is a scientific term for electrokinetic potential that expresses the
potential difference between the dispersion medium and fluid that is sticking over
the surface of the dispersed particles in the colloidal suspension (Kutscher et al.
2010). This is basically measured by two techniques: microelectrophoresis, which is
based on capturing the images of particles moving around, and the other one is electrophoretic light scattering, that is, based on dynamic light scattering (Kedar et al.
2010; Van Butsele et al. 2009). As discussed in the earlier sections, size and shape
of the NPs play a critical role in drug delivery. However, it has been observed that
negatively charged particles get easily opsonized and cleared by reticuloendothelial
system, mainly mediated by liver and spleen. Thus, variation in the surface charge
of the NPs can potentially aid in binding to the tissues (Chen et al. 2010; Patil et al.
2007; Reis et al. 2006). Cellular surfaces are rich in negatively charged proteoglycans that play a part in cellular proliferation, migration, and motility. Thus, NPs with
higher positive surface charge could show enhanced uptake by the cell. A study conducted by Patil et al. showed enhanced uptake of cerium oxide NPs, which had ZP of
−43 mV (Bernfield et al. 1999; Mislick and Baldeschwieler 1996). Whereas particles with less negative or positive charge did not show efficient uptake by the cells.
The uptake was highly pronounced due to electrostatic interactions. Interestingly, in
another study it was observed that NPs with lesser surface charge also showed uptake
by adsorption of negatively charged molecules on the cationic sites in the form of clusters. However, surface modification of NPs can alter the behavior of cellular uptake,
as in case of histidine substituted amino group of glycol chitosan self-assembled NPs.
Due to strong cationic nature of histidine at acidic pH, it is capable of interacting with
the endosomal membrane and its destabilization. Accordingly, the delivery of drugs
becomes convenient in case of cancer cells as well. Cancer cell surfaces are usually
negatively charged and acid-outside plasma pH gradients. This mediates stronger
interactions between cationic NPs and tumor tissues responsible for increased tumor
accumulation. This strategy is known as passive targeting or enhanced permeability
retention effect (EPR), where particle size along with the surface charge and stability
of the particles are known to contribute to the tumor accumulation (Park 2006; Staples et al. 2006). In similar to drug delivery through parenteral route, drug delivery