Hollow Mesoporous Silica/Poly(<scp>l</scp>-lysine) Particles for Codelivery of Drug and Gene with Enzyme-Triggered Release Property

Zhu, Yufang; Meng, Weina; Gao, Hong; Hanagata, Nobutaka

doi:10.1021/jp203454g

Cited by 121 publications

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“…This group also reported that the loading capacity of CpG oligodeoxynucleotide molecules was 30-40 µg/mg nanoparticles for poly-l-lysine-coated mesoporous SiO 2 nanoparticles with a size and specific surface area of 400-500 nm and 680 m 2 /g, respectively, but the capacity increased to about 100 µg/mg nanoparticles in a layer-by-layer assembly with CpG oligodeoxynucleotide molecules and poly-l-lysine. 36 Although flake-shell SiO 2 nanoparticles coated with PEI-600 showed the lowest loading capacity (97.7 ± 11.5 µg/mg nanoparticles) among the different Mns of PEI, the loading capacity was still comparable with or higher than that of mesoporous SiO 2 nanoparticles. Surface coating by polycations has limited usefulness for mesoporous SiO 2 nanoparticles because the polycations bury or cover the mesopores.…”

Section: Discussionmentioning

confidence: 88%

“…The specific surface area of the flake-shell SiO 2 nanoparticles was 83-fold higher than that of smooth-surfaced SiO 2 nanoparticles, and is similar to that of mesoporous SiO 2 nanoparticles with a similar diameter. 22,35,36 Such a large surface area makes it possible to load a large amount of nucleic acid drugs on the surface of flake-shell SiO 2 nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

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Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Manoharan¹,

Ji²,

Yamazaki³

et al. 2012

IJN

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Background Class B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules. Methods For improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO 2 nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO 2 nanoparticles were prepared by coating SiO 2 nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da). Results The capacity of the flake-shell SiO 2 nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO 2 nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO 2 nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO 2 nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO 2 nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO 2 nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO 2 nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO 2 nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Manoharan¹,

Ji²,

Yamazaki³

et al. 2012

IJN

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“…At the same time, calcium phosphate gradually dissolves in the acidic environment of the lysosome's interior, so the slow release of CpG ODN can be expected. Zhu et al 81 have…”

Section: Sustained Release Of Cpg Odnsmentioning

confidence: 99%

Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system

Hanagata¹

2012

IJN

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163

139

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Unmethylated cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are recognized by Toll-like receptor 9 (TLR9) found in antigen-presenting cells and B cells and can activate the immune system. Using CpG ODNs as an adjuvant has been found to be effective for treating infectious diseases, cancers, and allergies. Because natural ODNs with only a phosphodiester backbone are easily degraded by nuclease (deoxyribonuclease [DNase]) in serum, CpG ODNs with a phosphorothioate backbone have been studied for clinical application. CpG ODNs with a phosphorothioate backbone have raised concern regarding undesirable side effects; however, several CpG ODNs with only a phosphodiester backbone have been reported to be stable in serum and to show an immunostimulatory effect. In recent years, research has been conducted on delivery systems for CpG ODNs using nanoparticles (NPs). The advantages of NP-based delivery of CpG ODN include (1) it can protect CpG ODN from DNase, (2) it can retain CpG ODN inside the body for a long period of time, (3) it can improve the cellular uptake efficiency of CpG ODN, and (4) it can deliver CpG ODN to the target tissues. Because the target cells of CpG ODN are cells of the immune system and TLR9, the receptor of CpG ODN is localized in endolysosomes, CpG ODN delivery systems are required to have qualities different from other nucleic acid drugs such as antisense DNA and small interfering RNA. Studies until now have reported various NPs as carriers for CpG ODN delivery. This review presents DNase-resistant CpG ODNs with various structures and their immunostimulatory effects and also focuses on delivery systems of CpG ODNs that utilize NPs. Because CpG ODNs interact with TLR9 and activate both the innate and the adaptive immune system, the application of CpG ODNs for the treatment of cancers, infectious diseases, and allergies holds great promise.

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“…The polymer shells can provide colloidal stability, handle for chemoligation (targeting moieties) and improve the blood circulation lifetimes, which are crucial for efficient in vivo drug delivery. Various polymers have been reported as coating shells poly(L-lysine) (PLL), 22 poly(N-isopropylacrylamide), 23 poly (lactic acid) (PLA) 24 either in their native forms or as conjugates. However, the applicability of these functionalized MSNs is largely restricted to their compositions and the coating materials, whereby the loading efficiency is usually not high enough for a practical usage and the polymer shell also limits both drug loading and release from MSNs.…”

Section: Introductionmentioning

confidence: 99%

Chondroitin sulfate functionalized mesostructured silica nanoparticles as biocompatible carriers for drug delivery

Qin²,

Fan³

2012

IJN

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Mesoporous silica nanoparticles (MSNs) have garnered a great deal of attention as potential carriers for therapeutic payloads. Here, we report a pH-responsive drug-carrier based on chondroitin sulfate functionalized mesostructured silica nanoparticles (NMChS-MSNs) ie, the amidation between NMChS macromer and amino group functionalized MSNs. The prepared nanoparticles were characterized using dynamic light scattering, fourier transform infrared spectroscopy and transmission electron microscopy. The resultant NMChS-MSNs were uniform spherical nanoparticles with a mean diameter of approximately 74 nm. Due to the covalent graft of hydrophilic and pH responsive NMChS, the NMChS-MSNs could be well dispersed in aqueous solution, which is favorable to being utilized as drug carriers to construct a pH-responsive controlled drug delivery system. Doxorubicin hydrochloride (DOX), a well-known anticancer drug, could be effectively loaded into the channels of NMChS-MSNs through electrostatic interactions between drug and matrix. The drug release rate of DOX@NMChS-MSNs was pH dependent and increased with the decrease of pH. The in vitro cytotoxicity test indicated that NMChS-MSNs were highly biocompatible and suitable to use as drug carriers. Our results imply that chondroitin sulfate functionalized nanoparticles are promising platforms to construct the pH-responsive controlled drug delivery systems for cancer therapy.

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Hollow Mesoporous Silica/Poly(l-lysine) Particles for Codelivery of Drug and Gene with Enzyme-Triggered Release Property

Cited by 121 publications

References 50 publications

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system

Chondroitin sulfate functionalized mesostructured silica nanoparticles as biocompatible carriers for drug delivery

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Hollow Mesoporous Silica/Poly(l-lysine) Particles for Codelivery of Drug and Gene with Enzyme-Triggered Release Property

Cited by 121 publications

References 50 publications

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-&alpha;

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-&alpha;

Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system

Chondroitin sulfate functionalized mesostructured silica nanoparticles as biocompatible carriers for drug delivery

Contact Info

Product

Resources

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Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α