2.4 Visualized drug delivery and controlled release
Due to the excellent water-solubility, biocompatibility and
environmental friendliness of nonconventional polysiloxanes, they have
gained increasing attention in biological applications, such as drug
delivery and controlled release. Our group fabricated cell-targeting
HBPSi-Apt by covalently linking the AS1411 aptamer with HBPSi and used
it as a visual tracker for on-demand cell-targeting and intracellular
drug release.[47] As can be seen in figure 10A,
the AS1411 aptamer functionalized HBPSi selectively bound with
nucleolin-overexpressed cancer cells than normal cells, confirming its
on-demand drug delivery capability. When loaded with fluorescent DOX,
intracellular drug accumulation and release was observed. The
HBPSi-Apt@DOX incubated cells display uniformly distributed blue
fluorescence in the cell cytoplasm and time-dependent red fluorescence
in the cell nucleus, which is consist with the drug release process.
With the numerous amine groups in HBPSi and the disulfide bond in
HBPSi-Apt, HBPSi-Apt@DOX showed pH and GSH dual-responsive drug release
behavior (Figure 10B). The acidic and alkaline conditions affected the
charge of HBPSi-Apt@DOX and formed different electrostatic interactions,
thus accelerated the DOX release at pH 5.0. The presence of GSH cleaved
the disulfide bond in HBPSi-Apt and exposed the HBPSi core, leading to
an enhance DOX release rate.[47]
The terminal modification gives HBPSi controlled drug release
capability. The hydrophobic cavity inside β -CD is an excellent
hydrophobic drug carrier, thus the modification of β -CD improved
the drug loading capacity of HBPSi from 80.0 mg/g to 160.0 mg/mg with a
pH responsive release behavior.[38] The connection
with hydrophobic oleic acid also increases the ibuprofen loading
capacity of HBPSi, which reaches 470 mg/g due to the hydrophobic core in
the self-assembly structure.[45] The release rate
of ibuprofen obviously accelerated in solution with a pH of 5.5 or 6.4
than that in solution at pH 7.4 (Figure 10D). The pH-controlled drug
release behavior is caused by the electrostatic interactions between
HBPSi derivatives and ibuprofen.[38] In acidic
buffer, both HBPSi derivatives and ibuprofen are positively charged,
thus the charge repulsion promotes the drug release. On the contrary,
the surface charge of ibuprofen changes to negative at pH 7.4 and the
charge attraction suppresses its release.
The abundant terminal groups also make HBPSi an excellent candidate for
responsive prodrug. With the successive linking with
3,3′-dithiodipropionic acid anhydride and
10-hydroxycamptothecin, our group
prepared a HBPSi prodrug (HBPSi-SS-HCPT) that displayed pH and redox
dual-responsive drug release behavior.[39] The
ester bond endows the HBPSi prodrug with pH responsiveness, and the
disulfide bond in 3,3′-dithiodipropionic acid anhydride results in redox
responsiveness. The pH and GSH works synergistically, thus makes HBPSi
prodrug stable under physiological conditions, and burst drug release at
intratumoral pH and GSH. In vivo antitumor experiments
demonstrated efficient antitumor efficacy with a total tumor inhibition
rate of 27% within 15 days (Figure 10F-10H). Moreover, the fluorescent
nature of HBPSi also enables visualized drug delivery and releasein vivo .