Targeted drug delivery crossing cytoplasmic membranes of intended cells via ligand-grafted sterically stabilized liposomes

Lu, Jian; Jeon, Eun-Jung; Lee, Bao Shiang; Önyüksel, Hayat; Wang, Zaijie Jim

doi:10.1016/j.jconrel.2005.10.025

Cited by 27 publications

(24 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed size of liposome (1% octreotide ligand decoration as example) was approximately 100 nm ( Figure 1A), which was similar to hydrodynamic diameter obtained from the DLS. Post-insertion method had been proved to be an efficient method for liposomal modification (Uster et al, 1996, Iden & Allen, 2001, Lu et al, 2006. Not only because it showed excellent insertion efficiency as demonstrated here, but also due to the various density of octreotide-targeted liposomes came from a single preparation of P-L.…”

Section: Characterization Of Octreotide-targeted Liposomal Doxmentioning

confidence: 70%

“…Various density of Octreotide-targeted liposomes were obtained by post-insertion method (Paul S. Uster 1996, Ka-yun Ng (Ng et al, 2000), Debbie L. Iden, (Iden & Allen, 2001), Justin M. Saul (Saul et al, 2003), and Jian Lu (Lu et al, 2006). In brief, separate aliquots of blank liposome from a single batch were equilibrated at 40 C water bath and then different aliquot of concentrated HSPE-PEG-Octreotide solution was added at defined molar lipid-ligand ratio.…”

Section: Activity Determination Of Hspe-peg-octreotide By Synchronousmentioning

confidence: 99%

See 1 more Smart Citation

Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

Yuan

Sun

et al. 2016

Drug Delivery

View full text Add to dashboard Cite

Octreotide had been exploited as a targeting ligand for nanoparticle tumor localization overexpressing somatostatin receptor. In addition to particle size and other physiochemical properties, ligand density had great influence on the delivery of active targeted nanoparticles. Herein, octreotide-targeted liposomal doxorubicin was constructed with different ligand density by post-inserting HSPE-PEG 4000 -Octreotide into pre-formed liposome. The octreotide ligand insertion was confirmed by activity detection of octreotide in HSPE-PEG 4000 -Octreotide with synchronous fluorescence. 1% octreotide density could achieve the best uptake efficiency on NCI-H-446 and SMMC-7721 cell lines among all liposomes. Octreotide-grafted longcirculating liposome (Oct-SSL) was prepared based on 1% octreotide density. The results showed that the insertion of PEG reduced cellular uptake and cytotoxicity. However, Oct-SSL showed a higher MRT compared with Oct-L showing the relative higher long circulating effect in pharmacokinetic study. Oct-SSL also showed tumor growth inhibition of twofold compared with other groups in Heps xenograft model mice. Oct-SSL with suitable ligand density and PEG modification exhibited significant effective tumor targeting for antitumor drug delivery.

show abstract

Section: Characterization Of Octreotide-targeted Liposomal Doxmentioning

confidence: 70%

Section: Activity Determination Of Hspe-peg-octreotide By Synchronousmentioning

confidence: 99%

Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

Yuan

Sun

et al. 2016

Drug Delivery

View full text Add to dashboard Cite

show abstract

“…22,23 First, an anti-MSLN mAb was incubated with Traut's reagent at a molar ratio of 1:100 in PBS (pH 7.4) for 2 hours for antibody thiolation. To remove excess Traut's reagent, the thiolated antibody was further dialyzed in PBS (pH 7.4) with 5 mM EDTA for 24 hours.…”

Section: Conjugation Of Anti-msln Monoclonal Antibodymentioning

confidence: 99%

A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

Deng¹,

Ke²,

He³

et al. 2012

IJN

View full text Add to dashboard Cite

Pancreatic cancer is a highly lethal disease with a 5-year survival rate less than 5% due to the lack of an early diagnosis method and effective therapy. To provide a novel early diagnostic method and targeted therapy for pancreatic cancer, a multifunctional nanoimmunoliposome with high loading of ultrasmall superparamagnetic iron oxides (USPIOs) and doxorubicin (DOX) was prepared by transient binding and reverse-phase evaporation method, and was conjugated with anti-mesothelin monoclonal antibody by post-insertion method to target anti-mesothelin-overexpressed pancreatic cancer cells. The in vitro and in vivo properties of this anti-mesothelin antibody-conjugated PEGlyated liposomal DOX and USPIOs (M-PLDU; and PEGlyated nanoimmunoliposome without antibody conjugation [PLDU]) were evaluated both in human pancreatic cancer cell line Panc-1 cell and in a pancreatic cancer xenograft animal model. Results showed that M-PLDUs were spherical and uniform with a diameter about ∼180 nm, with a zeta potential of about −28∼−30 mV, and had good efficacy encapsulating DOX and USPIOs. The in vitro study demonstrated that M-PLDUs possessed good magnetic resonance imaging (MRI) capability with a transverse relaxivity (r 2 ) of about 58.5 mM -1 ⋅ s -1 . Confocal microscopy showed more efficient uptake of M-PLDU in Panc-1 cells by antibodymediated targeting. Methyl thiazolyl tetrazolium assay results showed significant inhibitory effect of M-PLDU against Panc-1 cells (half-maximal inhibitory concentration, 1.95 µM). The in vivo imaging study showed that the tumor signal intensity (SI) dropped significantly about 4 hours after intravenous injection of M-PLDU. The decrease in tumor SI induced by M-PLDUs (∆SI = 145.98 ± 20.45) or PLDUs (∆SI = 75.69 ± 14.53) was much more significant than that by free USPIOs (∆SI = 42.78 ± 22.12; P , 0.01). The in vivo antitumor study demonstrated that compared with FD (free DOX) and PLDU, M-PLDU possessed higher inhibitory effect on tumor growth and the tissue distribution assay further proved that M-PLDUs could selectively accumulate in the tumor xenograft. These results indicated that M-PLDU not only well retained the inherent MRI capability of USPIOs, but significantly improved the targeting distribution of USPIOs and therapeutic agents in pancreatic tumor tissues. They may serve as a promising theranostic nanomedicine not only for early detection but also for MRI-monitored targeting therapy of human pancreatic cancer.

show abstract

“…The concept of targeting always exploits phenotypic differences between the disease target and normal tissues that are then translated into a dose differential between the target and off-target sites. Current methods involve the use of antibodies and other ligands to deliver agents (peptides, nucleotides, hydrophobic drugs) to selected extracellular and intracellular targets (119). Antibodies have the advantage of high specificity, but they are expensive, time-consuming to produce, and have problems with stability and storage.…”

Section: Strategies For Pec Targeted Delivery Of Therapeuticsmentioning

confidence: 99%

Multifunctional Nanoparticulate Polyelectrolyte Complexes

et al. 2007

View full text Add to dashboard Cite

Water-soluble, biodegradable, polymeric, polyelectrolyte complex dispersions (PECs) have evolved because of the limitations, in terms of toxicity, of the currently available systems. These aqueous nanoparticulate architectures offer a significant advantage for products that may be used as drug delivery systems in humans. PECs are created by mixing oppositely charged polyions. Their hydrodynamic diameter, surface charge, and polydispersity are highly dependent on concentration, ionic strength, pH, and molecular parameters of the polymers that are used. In particular, the complexation between polyelectrolytes with significantly different molecular weights leads to the formation of water-insoluble aggregates. Several PEC characteristics are favorable for cellular uptake and colloidal stability, including hydrodynamic diameter less than 200 nm, surface charge of >30 mV or <-30 mV, spherical morphology, and polydispersity index (PDI) indicative of a homogeneous distribution. Maintenance of these properties is critical for a successful delivery vehicle. This review focuses on the development and potential applications of PECs as multi-functional, site-specific nanoparticulate drug/gene delivery and imaging devices.

show abstract

Targeted drug delivery crossing cytoplasmic membranes of intended cells via ligand-grafted sterically stabilized liposomes

Cited by 27 publications

References 47 publications

Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

Multifunctional Nanoparticulate Polyelectrolyte Complexes

Contact Info

Product

Resources

About