255
MEB55-loaded GSH/pH-NS demonstrated greater inhibition of
DU145 cell (high GSH content) viability in MTT assays compared
to free MEB55. In contrast, they had a lower effect on the viability
of PC-3 cells (low GSH content). LDH assays revealed that treatment with the GSH/pH-NS resulted in cell death, which was
dependent on the intracellular GSH content. Treatment with free
SLs also induced cell death in PC-3 cells, which was likely related
to oxidative stress. Limited LDH release was observed in the other
cell types 24 h after treatment. Annexin-V staining indicated that
the DU145 cells underwent apoptotic cell death, and colony formation assays confirmed the dependence of the cellular responses
on the intracellular GSH content. The incorporation of two SLs
into GSH/pH-NS enhanced their cytotoxic effects on prostate
cancer cells indicating that GSH/pH-NS are dual-stimuliresponsive nanocarriers that may favor the selectively controlled
release of SLs in target cancer cells [45].
Ailanthone is a natural active compound isolated from the
Ailanthus altissima tree, which has been shown to possess an in
vitro growth inhibitory effect against several cancer cell lines.
Advanced bladder cancer is a common disease characterized by a
frequent onset of resistance to cisplatin-based therapy. It has been
demonstrated on bladder cancer cells, and the cisplatin resistance
(CDDP) is accompanied by an increase in Nrf2 protein expression
which contributes to conferring CDDP resistance. Indeed, Nrf2
overexpression is associated with clinically relevant CDDP resistance in bladder cancer patients [46]. Increasing evidence has
demonstrated the involvement of YAP, a key component of the
Hippo tumor-suppressor pathway, in chemoresistance of several
types of cancers. Ailanthone is able to inhibit proliferation in resistant cells. Incorporating it in similar nanocarriers can improve the
anticancer therapeutic activity [47].
Erlotinib belongs to BCS II class drugs approved initially for
non-small cell lung cancer, and is an epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitor. Its potential in the
treatment of various other cancers such as breast cancer, locally
advanced or metastatic non-small cell lung cancer, ovarian cancer,
glioma, head and neck cancer, and colorectal cancer has also been
demonstrated. Systemic and uncontrolled administration of erlotinib hydrochloride (ERL) is associated with severe toxicity [48].
One study utilized previously synthesized and characterized
NS based on the reaction between β-cyclodextrin monomer and
CDI cross-linker. The solubility of ERL was optimum in 1:4 w/w
proportions of drug and NS; solubility of all complexes ERL-NS
was significantly higher (p < 0.01) than pure ERL (3.16 ± 0.73 μg/
mL). ERL-NS was found to be more cytotoxic against both MIA
PaCa-2 and PANC-1 cells compared to free ERL. When incubated
with MIA PaCa-2 and PANC-1 pancreatic cells, IC 50 values of
ERL-NS in each time frame (24 h, 48 h, and 72 h) were significantly
Drug-Encapsulated Cyclodextrin Nanosponges
MEB55-loaded GSH/pH-NS demonstrated greater inhibition of
DU145 cell (high GSH content) viability in MTT assays compared
to free MEB55. In contrast, they had a lower effect on the viability
of PC-3 cells (low GSH content). LDH assays revealed that treatment with the GSH/pH-NS resulted in cell death, which was
dependent on the intracellular GSH content. Treatment with free
SLs also induced cell death in PC-3 cells, which was likely related
to oxidative stress. Limited LDH release was observed in the other
cell types 24 h after treatment. Annexin-V staining indicated that
the DU145 cells underwent apoptotic cell death, and colony formation assays confirmed the dependence of the cellular responses
on the intracellular GSH content. The incorporation of two SLs
into GSH/pH-NS enhanced their cytotoxic effects on prostate
cancer cells indicating that GSH/pH-NS are dual-stimuliresponsive nanocarriers that may favor the selectively controlled
release of SLs in target cancer cells [45].
Ailanthone is a natural active compound isolated from the
Ailanthus altissima tree, which has been shown to possess an in
vitro growth inhibitory effect against several cancer cell lines.
Advanced bladder cancer is a common disease characterized by a
frequent onset of resistance to cisplatin-based therapy. It has been
demonstrated on bladder cancer cells, and the cisplatin resistance
(CDDP) is accompanied by an increase in Nrf2 protein expression
which contributes to conferring CDDP resistance. Indeed, Nrf2
overexpression is associated with clinically relevant CDDP resistance in bladder cancer patients [46]. Increasing evidence has
demonstrated the involvement of YAP, a key component of the
Hippo tumor-suppressor pathway, in chemoresistance of several
types of cancers. Ailanthone is able to inhibit proliferation in resistant cells. Incorporating it in similar nanocarriers can improve the
anticancer therapeutic activity [47].
Erlotinib belongs to BCS II class drugs approved initially for
non-small cell lung cancer, and is an epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitor. Its potential in the
treatment of various other cancers such as breast cancer, locally
advanced or metastatic non-small cell lung cancer, ovarian cancer,
glioma, head and neck cancer, and colorectal cancer has also been
demonstrated. Systemic and uncontrolled administration of erlotinib hydrochloride (ERL) is associated with severe toxicity [48].
One study utilized previously synthesized and characterized
NS based on the reaction between β-cyclodextrin monomer and
CDI cross-linker. The solubility of ERL was optimum in 1:4 w/w
proportions of drug and NS; solubility of all complexes ERL-NS
was significantly higher (p < 0.01) than pure ERL (3.16 ± 0.73 μg/
mL). ERL-NS was found to be more cytotoxic against both MIA
PaCa-2 and PANC-1 cells compared to free ERL. When incubated
with MIA PaCa-2 and PANC-1 pancreatic cells, IC 50 values of
ERL-NS in each time frame (24 h, 48 h, and 72 h) were significantly
Drug-Encapsulated Cyclodextrin Nanosponges