Abstract:Competitive binding activated nanovalves (CBAN) with ondemand activation capability are fabricated through switching from host-guest complexation to decomplexation upon the introduction of competitive guest (C-guest) molecules. Guest molecules of pyrene or naphthalene are used to associate with b-cyclodextrin (b-CD) host to form supramolecular complexes. These supramolecular conjugations were assembled on the surface of mesoporous silica nanoparticles (MSNs), which played a role of "nanovalve" for blocking the… Show more
“…By comparing with UCMS showing no emission peak, the individual emission of UCMS-S-BP at 320 nm indicates that the thioether linker is successfully grafted on the surface of UCMS nanoparticles. After association of thioether linker with β -CD via host/guest interaction ( β -CD capping), a further increase in intensity at 320 nm for UCMS-S-BP@ β -CD is observed in agreement with the literature40 which demonstrates a successful modification of -S-BP linker and its capability of β -CD capping. TGA measurements (Figure 2C) also showed an obvious decrease in weight of the stepwise functionalized nanoparticles, indicating a successful surface functionalization and β -CD capping.Figure 2( A ) UV-Vis absorption spectra of BP, UCMS-SH, and UCMS–S-BP.…”
Background:
The design of novel nanoparticles with higher therapeutic efficacy and lower side effects, is still difficult but encouraging in cancer therapy. Specifically, for upconversion nanoparticles (UCNP)-based drug release, a high intensity of NIR light (1.4~5.0 W/cm
2
) above the maximum permissible exposure (0.33 W/cm
2
for 980 nm) is commonly used and severely limits its practical application.
Methods:
The highly emissive UCNP is first synthesized and then coated with mesoporous silica (MS) shell (UCMS). Next, the surface of UCMS is modified with the thioether (-S-BP) linker, leading to UCMS-S-BP nanoparticles. Finally, after the drug doxorubicin (Dox) is loaded into the pore channels of UCMS, the pore openings are blocked by the
β
-cyclodextrin (
β
-CD) gatekeeper through the association with the -S-BP linker (UCMS(Dox)-S-BP@
β
-CD).
Results:
Upon 980 nm NIR light irradiation with an ultralow intensity of 0.30 W/cm
2
, it is found that the loaded Dox can be released through the cleavage of thioether linkers triggering dissociation of
β
-CD gatekeepers. The in vitro results exhibited significantly therapeutic efficacy with 85.2% of HeLa cells killed in this study.
Conclusions:
An ultralow-intensity NIR light triggered on-demand drug release system has been developed by employing highly emissive UCNP and photocleavable linker with low bond dissociation energy to avoid the potential photodamage on healthy neighbor cells.
“…By comparing with UCMS showing no emission peak, the individual emission of UCMS-S-BP at 320 nm indicates that the thioether linker is successfully grafted on the surface of UCMS nanoparticles. After association of thioether linker with β -CD via host/guest interaction ( β -CD capping), a further increase in intensity at 320 nm for UCMS-S-BP@ β -CD is observed in agreement with the literature40 which demonstrates a successful modification of -S-BP linker and its capability of β -CD capping. TGA measurements (Figure 2C) also showed an obvious decrease in weight of the stepwise functionalized nanoparticles, indicating a successful surface functionalization and β -CD capping.Figure 2( A ) UV-Vis absorption spectra of BP, UCMS-SH, and UCMS–S-BP.…”
Background:
The design of novel nanoparticles with higher therapeutic efficacy and lower side effects, is still difficult but encouraging in cancer therapy. Specifically, for upconversion nanoparticles (UCNP)-based drug release, a high intensity of NIR light (1.4~5.0 W/cm
2
) above the maximum permissible exposure (0.33 W/cm
2
for 980 nm) is commonly used and severely limits its practical application.
Methods:
The highly emissive UCNP is first synthesized and then coated with mesoporous silica (MS) shell (UCMS). Next, the surface of UCMS is modified with the thioether (-S-BP) linker, leading to UCMS-S-BP nanoparticles. Finally, after the drug doxorubicin (Dox) is loaded into the pore channels of UCMS, the pore openings are blocked by the
β
-cyclodextrin (
β
-CD) gatekeeper through the association with the -S-BP linker (UCMS(Dox)-S-BP@
β
-CD).
Results:
Upon 980 nm NIR light irradiation with an ultralow intensity of 0.30 W/cm
2
, it is found that the loaded Dox can be released through the cleavage of thioether linkers triggering dissociation of
β
-CD gatekeepers. The in vitro results exhibited significantly therapeutic efficacy with 85.2% of HeLa cells killed in this study.
Conclusions:
An ultralow-intensity NIR light triggered on-demand drug release system has been developed by employing highly emissive UCNP and photocleavable linker with low bond dissociation energy to avoid the potential photodamage on healthy neighbor cells.
“…The surface of UCNP@mSiO 2 was subsequently immobilized with hydrophobic DNQ as the guest stalk molecule. After doxorubicin hydrochloride (DOX, a universal anticancer drug) was loaded into the channels of mSiO 2 shell, β-cyclodextrin (β-CD) − with a hydrophobic cavity was added as a host gatekeeper to cap DNQ host molecules via hydrophobic affinity, which play a role in the OFF state of the nanovalves to prevent the drug from being released (Scheme e). Upon 980 nm light irradiation, a NIR light-triggered hydrophobic-to-hydrophilic switch due to the transformation of hydrophobic DNQ to hydrophilic 3-indenecarboxylic acid (ICA) , took place so that the capped β-CD gatekeepers dissociate as the result of repulsion between hydrophobic β-CD and hydrophilic ICA, activating the ON state of the nanovalves to release drug triggering on-demand cancer therapy (Scheme f).…”
An on-demand drug delivery nanoplatform based on mesoporous silica (mSiO 2 ) coated upconversion nanoparticles (UCNP@mSiO 2 ) with a novel near-infrared (NIR) light-triggered hydrophobic-to-hydrophilic switch nanovalve was fabricated. The surface of UCNP@mSiO 2 was first immobilized with hydrophobic 2-diazo-1,2-naphthoquinones (DNQ) guest molecules. After doxorubicin hydrochloride (DOX, a universal anticancer drug) was loaded into channels of mSiO 2 shell, β-cyclodextrin (β-CD) host molecules with a hydrophobic cavity were added as gatekeepers to cap DNQ stalk molecules via hydrophobic affinity, which may play a role in the OFF state of the nanovalve to prevent the drug from being released. Upon 980 nm light irradiation, a NIR light-triggered hydrophobic-to-hydrophilic switch, that transformed the hydrophobic guest DNQ into hydrophilic guest 3-indenecarboxylic acid (ICA), took place so that the capped β-CD gatekeepers dissociated due to repulsion between β-CD host (hydrophobic) and ICA guest (hydrophilic), activating the ON state of the nanovalves to release drug. The in vitro studies prove that the nanoplatform enables on-demand drug release to efficiently kill HeLa cell upon NIR light regulation. The in vivo experiment results further confirm that the nanoplatform with such fabricated nanovalves is able to inhibit tumor growth in mice. The designed nanovalves based on the novel NIR light-triggered hydrophobic-to-hydrophilic switch strategy therefore may shed new light on future development of on-demand cancer therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
