confirmed that these nanoparticles had no acute toxicity and were safe to be used for
drug delivery. Next, paclitaxel-loaded nanoparticles were used against multiple
tumor-cell lines to determine their bioactivity. Results confirmed that nanoparticles
were efficient drug delivery platform to deliver drug to B16F10, HeLa, HepG2,
MCF-7, and MDA-MB-231 cells. Moreover, paclitaxel-loaded nanoparticles show
increased in vitro efficacy to PTX-resistant cancer cells. Lastly, paclitaxel-loaded
nanoparticles were used on tumor-bearing mice model and discovered to suppress
tumor growth. As a consequence, acetalated α-CD was a pH-responsive nanomaterial for the delivery of antitumor drugs in vitro and in vivo.
Polyvalency is a useful strategy to assemble stable nanoparticles. Namgung et al.
reported nano-assembly based on poly-CD and poly-paclitaxel for antitumor therapy
[22]. Authors used poly-CD as a biocompatible biomaterial. Polyvalency supramolecular interaction between CD and paclitaxel assisted the formation of nanoparticles, which were further stabilized by hydrogen-bond between CDs. These
nanoparticles could disassemble due to dilution, salt, or free CD competition.
Paclitaxel was conjugated to polymer backbone by ester bond, which could degrade
to release free paclitaxel triggered by esterase. These nano-assemblies were evaluated against several tumor-cell lines in vitro and demonstrated potent bioactivity. For
MCF-7 cells, nano-assemblies had an IC 50 of 120-fold lower compared to that of free
paclitaxel. Before nano-assembly was used for in vivo study, hemolysis assay was
carried out to confirm the biocompatibility of these nano-assemblies. Then, nanoassemblies were used against two tumor models: human colon cancer HCT-8 cells
and human breast cancer MDA-MB-231 cells. For both tumor models, nanoassemblies had good efficacy with high suppression effect toward tumor volume
growth. Biodistribution study was carried out with MCF-7 or MDA-MB-231 tumorbearing mice. It was discovered that for both tumor models, nano-assemblies were
accumulated and cleared by the liver, kidney, and gastrointestinal tract. There were
decent accumulations of paclitaxel in tumor with a relatively higher tumor accumulation for MDA-MB-231 tumor model. This work demonstrated the interplay of
host-guest interaction and multivalency for drug delivery applications, and supramolecular interaction is a powerful tool to conveniently construct nanoscale DDSs.
Zhang et al. took advantage of paclitaxel-conjugated CD to assemble photocontrolled reversible microtubule [23]. As shown in Fig. 7, microtubule (MT)
assembly was obtained by mixing CD derivative (PTX-CD) and paclitaxel-modified
photochromic arylazopyrazole (PTX-AAP) as a result of host-guest interaction
between CD and AAP. MTs were photo-switched by UV-irradiation due to configuration transition of azobenzene. Self-assembly of PTX-CD and PTX-AAP could
form different types of nanoscale architectures, which were carefully characterized
by transmission electron microscopy (TEM). Fluorescence-dye-staining assays were
exploited to study the complexation-induced intertubular aggregation at the cellular
level. Normal MTs were uniformly distributed in the whole cell. By contrast,
nanoparticulate aggregates of approximately 4–8 μm were formed around cell nuclei
in the trans-MT group, which could trigger the cell death. Therefore, photocontrolled microtubule morphology change could be used to switch on or switch
off cell cytotoxicity, which is a new strategy for disease diagnosis and treatment.
23 Stimuli-Responsive Self-Assembly Based on Macrocyclic Hosts and Biomedical. . .
615
drug delivery. Next, paclitaxel-loaded nanoparticles were used against multiple
tumor-cell lines to determine their bioactivity. Results confirmed that nanoparticles
were efficient drug delivery platform to deliver drug to B16F10, HeLa, HepG2,
MCF-7, and MDA-MB-231 cells. Moreover, paclitaxel-loaded nanoparticles show
increased in vitro efficacy to PTX-resistant cancer cells. Lastly, paclitaxel-loaded
nanoparticles were used on tumor-bearing mice model and discovered to suppress
tumor growth. As a consequence, acetalated α-CD was a pH-responsive nanomaterial for the delivery of antitumor drugs in vitro and in vivo.
Polyvalency is a useful strategy to assemble stable nanoparticles. Namgung et al.
reported nano-assembly based on poly-CD and poly-paclitaxel for antitumor therapy
[22]. Authors used poly-CD as a biocompatible biomaterial. Polyvalency supramolecular interaction between CD and paclitaxel assisted the formation of nanoparticles, which were further stabilized by hydrogen-bond between CDs. These
nanoparticles could disassemble due to dilution, salt, or free CD competition.
Paclitaxel was conjugated to polymer backbone by ester bond, which could degrade
to release free paclitaxel triggered by esterase. These nano-assemblies were evaluated against several tumor-cell lines in vitro and demonstrated potent bioactivity. For
MCF-7 cells, nano-assemblies had an IC 50 of 120-fold lower compared to that of free
paclitaxel. Before nano-assembly was used for in vivo study, hemolysis assay was
carried out to confirm the biocompatibility of these nano-assemblies. Then, nanoassemblies were used against two tumor models: human colon cancer HCT-8 cells
and human breast cancer MDA-MB-231 cells. For both tumor models, nanoassemblies had good efficacy with high suppression effect toward tumor volume
growth. Biodistribution study was carried out with MCF-7 or MDA-MB-231 tumorbearing mice. It was discovered that for both tumor models, nano-assemblies were
accumulated and cleared by the liver, kidney, and gastrointestinal tract. There were
decent accumulations of paclitaxel in tumor with a relatively higher tumor accumulation for MDA-MB-231 tumor model. This work demonstrated the interplay of
host-guest interaction and multivalency for drug delivery applications, and supramolecular interaction is a powerful tool to conveniently construct nanoscale DDSs.
Zhang et al. took advantage of paclitaxel-conjugated CD to assemble photocontrolled reversible microtubule [23]. As shown in Fig. 7, microtubule (MT)
assembly was obtained by mixing CD derivative (PTX-CD) and paclitaxel-modified
photochromic arylazopyrazole (PTX-AAP) as a result of host-guest interaction
between CD and AAP. MTs were photo-switched by UV-irradiation due to configuration transition of azobenzene. Self-assembly of PTX-CD and PTX-AAP could
form different types of nanoscale architectures, which were carefully characterized
by transmission electron microscopy (TEM). Fluorescence-dye-staining assays were
exploited to study the complexation-induced intertubular aggregation at the cellular
level. Normal MTs were uniformly distributed in the whole cell. By contrast,
nanoparticulate aggregates of approximately 4–8 μm were formed around cell nuclei
in the trans-MT group, which could trigger the cell death. Therefore, photocontrolled microtubule morphology change could be used to switch on or switch
off cell cytotoxicity, which is a new strategy for disease diagnosis and treatment.
23 Stimuli-Responsive Self-Assembly Based on Macrocyclic Hosts and Biomedical. . .
615