Porous silicon–graphene oxide core–shell nanoparticles for targeted delivery of siRNA to the injured brain

Joo, Jinmyoung; Kwon, Ester J.; Kang, Jinyoung; Skalak, Matthew; Anglin, Emily J.; Mann, Aman P.; Ruoslahti, Erkki; Bhatia, Sangeeta N.; Sailor, Michael J.

doi:10.1039/c6nh00082g

Cited by 86 publications

(50 citation statements)

References 60 publications

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“…The release kinetics of the peptide payload, determined by measuring fluorescence intensity from the 6‐FAM label in the supernatant (after separation from the PSiNPs by centrifugation), matched the aqueous degradation profile of the PSiNPs: the loss in PL intensity from the PSiNPs correlated linearly with the appearance of fluorescence from the FAM label (Figure S5c, Supporting Information). This correlation between drug release and decrease in steady‐state PL intensity has been reported previously for the release of siRNA, protein, and small molecule payloads from porous Si particles . However, the time‐resolved PL spectrum has not previously been used to monitor payload release from a porous Si delivery vehicle.…”

Section: Methodssupporting

confidence: 70%

Tracking the Fate of Porous Silicon Nanoparticles Delivering a Peptide Payload by Intrinsic Photoluminescence Lifetime

et al. 2018

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A nanoparticle system for systemic delivery of therapeutics is described, which incorporates a means of tracking the fate of the nanocarrier and its residual drug payload in vivo by photoluminescence (PL). Porous silicon nanoparticles (PSiNPs) containing the proapoptotic antimicrobial peptide payload, [KLAKLAK] , are monitored by measurement of the intrinsic PL intensity and the PL lifetime of the nanoparticles. The PL lifetime of the PSiNPs is on the order of microseconds, substantially longer than the nanosecond lifetimes typically exhibited by conventional fluorescent tags or by autofluorescence from cells and tissues; thus, emission from the nanoparticles is readily discerned in the time-resolved PL spectrum. It is found that the luminescence lifetime of the PSiNP host decreases as the nanoparticle dissolves in phosphate-buffered saline solution (37 °C), and this correlates with the extent of release of the peptide payload. The time-resolved PL measurement allows tracking of the in vivo fate of PSiNPs injected (via tail vein) into mice. Clearance of the nanoparticles through the liver, kidneys, and lungs of the animals is observed. The luminescence lifetime of the PSiNPs decreases with increasing residence time in the mice, providing a measure of half-life for degradation of the drug nanocarriers.

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Section: Methodssupporting

confidence: 70%

Tracking the Fate of Porous Silicon Nanoparticles Delivering a Peptide Payload by Intrinsic Photoluminescence Lifetime

et al. 2018

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“…22 They have a high loading capacity for therapeutic payloads, which are released upon dissolution of the nanostructure, and this release can be controlled. 22, 49–51 Finally, pSiNPs, and nanoparticles in general, are well suited for targeting with peptides because the avidity effect provided by the multivalent presentation on the NP surface compensates for the relatively low affinity of peptides for their target. 27 …”

Section: Discussionmentioning

confidence: 99%

Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy

et al. 2018

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Bacterial resistance to antibiotics has made it necessary to resort to antibiotics that have considerable toxicities. Here, we show that the cyclic 9-amino acid peptide CARGGLKSC (CARG), identified via phage display on Staphylococcus aureus (S. aureus) bacteria and through in vivo screening in mice with S. aureus-induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in S. aureus-infected tissues and reduces the needed overall systemic dose, minimizing side effects. CARG binds specifically to S. aureus bacteria but not Pseudomonas bacteria in vitro, selectively accumulates in S. aureus-infected lungs and skin of mice but not in non-infected tissue and Pseudomonas-infected tissue, and significantly enhances the accumulation of intravenously injected vancomycin-loaded porous silicon nanoparticles bearing the peptide in S. aureus-infected mouse lung tissue. The targeted nanoparticles more effectively suppress staphylococcal infections in vivo relative to equivalent doses of untargeted vancomycin nanoparticles or of free vancomycin. The therapeutic delivery of antibiotic-carrying nanoparticles bearing peptides targeting infected tissue may help combat difficult-to-treat infections.

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“…The common silica functionalization reagent (3‐aminopropyl)‐dimethylethoxysilane places a positively charged amine group on the surface of the inner pore walls, and this combined with a graphene oxide shell allowed entrapment of siRNA in pSi nanoparticles that induced 65% gene silencing effect in vitro. By targeting the compromised blood‐brain barrier (BBB) in a mouse brain injury model and through the agency of the RVG (rabies virus glycoprotein) peptide, this system was able to achieve enhanced siRNA‐delivery efficiency in vivo . A similar structure, lacking the graphene oxide shell and conjugated with the CAQK brain injury targeting peptide attained 70% gene silencing effect in vitro .…”

Section: Protective Carriers For Sirna Deliverymentioning

confidence: 99%

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201903637.With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.

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Porous silicon–graphene oxide core–shell nanoparticles for targeted delivery of siRNA to the injured brain

Cited by 86 publications

References 60 publications

Tracking the Fate of Porous Silicon Nanoparticles Delivering a Peptide Payload by Intrinsic Photoluminescence Lifetime

Tracking the Fate of Porous Silicon Nanoparticles Delivering a Peptide Payload by Intrinsic Photoluminescence Lifetime

Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

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