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A. S. Shinde et al.
reservoir. The cyclodextrin gatekeeper can be cleaved at the ester linkage present in
the stalk part by lipase, releasing the guest molecules from the channel. Investigation
of different categories, for the controlled DDS that uses various gate based on the
surface of MSNs, such as AuNPs, AgNPs, dendrimer, and other gatekeepers [34].
Among the investigated DDS that are structurally stable, Bio-MSNs are suited to be
the best candidate, because of its advantages in intracellular delivery, due to larger
area of surface, tunable pore sizes, and volumes, and encapsulation of various drugs,
proteins and biogenic molecules [35].
Also, to achieve the goal of the controlled release of the drug, nano-carriers
been designed to have environment-sensitive delivery. Recently, with the help of
the self-assembly approach, a pH/thermo-responsive nano-carriers were fabricated
with dually responsive poly (N-isopropyl- acrylamide) (PNiPAM)-co-acrylic acid
(AA) hydrogel core coated with silica. These core-shell particles are uniform sized
with better dispersity as compared with MSNs. In in vitro studies, the nano-carriers
are more biocompatible and less cytotoxic. Also, the controlled drug release results
specify that PNiPAM/AA@SiO 2 particles are responsive in a pH-sensitive environment with the higher releasing efficiency as compared with the MSN particles, which
is a desirable trait for cancer treatment [36].
6 Multidrug Resistance
In cancer treatment, drug-sensitive cells are killed, while the proportion of the drugresistant cells are left out known to be multidrug resistance (MDR). The integral
membrane protein also is known to be MDR transporters increases the drug efflux,
which is the most common mechanism observed in MDR. The transporters such
as multidrug resistance-associated proteins (MRPs) and p-glycoprotein (MDR1)
reduces intracellular drug dose below the lethal threshold level by actively pumping
the chemotherapeutic drug out of the cell [37]. The use of nanomaterials has provided
a solution to this limitation and helps to bypass the MDR transporters. For example,
SP1049C is an innovative micellar formulation of DOX, which manifests greater
efficiency then DOX alone at odds with different drug-resistant tumor cell lines and
helps to circumvent p-glycoprotein-mediated drug resistance [38]. However, nanocarriers bypassing the transporters are not sufficient to overcome drug efflux. The
mechanism of drug efflux is due to the overexpression of transporters in the cancer
cells. Knockdown of the gene expression for the transporters using siRNA could help
reinstate the intracellular drug concentrations which are required for the induction of
apoptosis and cell cytotoxicity. Thus, nano-based co-delivery systems are designed
to target the transporters along with the delivery of the drug to increase the intracellular drug concentration. Meng et al. have reported MSNs to be functionalized with
DOX along with the p-glycoprotein siRNA (to silence the expression of the efflux
transporter) to an MDR cancer cell line synergistically [39].
A. S. Shinde et al.
reservoir. The cyclodextrin gatekeeper can be cleaved at the ester linkage present in
the stalk part by lipase, releasing the guest molecules from the channel. Investigation
of different categories, for the controlled DDS that uses various gate based on the
surface of MSNs, such as AuNPs, AgNPs, dendrimer, and other gatekeepers [34].
Among the investigated DDS that are structurally stable, Bio-MSNs are suited to be
the best candidate, because of its advantages in intracellular delivery, due to larger
area of surface, tunable pore sizes, and volumes, and encapsulation of various drugs,
proteins and biogenic molecules [35].
Also, to achieve the goal of the controlled release of the drug, nano-carriers
been designed to have environment-sensitive delivery. Recently, with the help of
the self-assembly approach, a pH/thermo-responsive nano-carriers were fabricated
with dually responsive poly (N-isopropyl- acrylamide) (PNiPAM)-co-acrylic acid
(AA) hydrogel core coated with silica. These core-shell particles are uniform sized
with better dispersity as compared with MSNs. In in vitro studies, the nano-carriers
are more biocompatible and less cytotoxic. Also, the controlled drug release results
specify that PNiPAM/AA@SiO 2 particles are responsive in a pH-sensitive environment with the higher releasing efficiency as compared with the MSN particles, which
is a desirable trait for cancer treatment [36].
6 Multidrug Resistance
In cancer treatment, drug-sensitive cells are killed, while the proportion of the drugresistant cells are left out known to be multidrug resistance (MDR). The integral
membrane protein also is known to be MDR transporters increases the drug efflux,
which is the most common mechanism observed in MDR. The transporters such
as multidrug resistance-associated proteins (MRPs) and p-glycoprotein (MDR1)
reduces intracellular drug dose below the lethal threshold level by actively pumping
the chemotherapeutic drug out of the cell [37]. The use of nanomaterials has provided
a solution to this limitation and helps to bypass the MDR transporters. For example,
SP1049C is an innovative micellar formulation of DOX, which manifests greater
efficiency then DOX alone at odds with different drug-resistant tumor cell lines and
helps to circumvent p-glycoprotein-mediated drug resistance [38]. However, nanocarriers bypassing the transporters are not sufficient to overcome drug efflux. The
mechanism of drug efflux is due to the overexpression of transporters in the cancer
cells. Knockdown of the gene expression for the transporters using siRNA could help
reinstate the intracellular drug concentrations which are required for the induction of
apoptosis and cell cytotoxicity. Thus, nano-based co-delivery systems are designed
to target the transporters along with the delivery of the drug to increase the intracellular drug concentration. Meng et al. have reported MSNs to be functionalized with
DOX along with the p-glycoprotein siRNA (to silence the expression of the efflux
transporter) to an MDR cancer cell line synergistically [39].