Targeted Cell Uptake of a Noninternalizing Antibody Through Conjugation to Iron Oxide Nanoparticles in Primary Central Nervous System Lymphoma

Wang, Tingzhong; Kievit, Forrest M.; Veiseh, Omid; Arami, Hamed; Stephen, Zachary R.; Chen, Fang; Liu, Yunhui; Ellenbogen, Richard G.; Zhang, Miqin

doi:10.1016/j.wneu.2013.01.011

Cited by 25 publications

(15 citation statements)

References 50 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was well correlated with other studies that have reported the development of targeted Nps. 32,[48][49][50] Thus, the tumor uptake of these Nps would take place specifically via an EGFR-mediated uptake mechanism. Cell cycle analysis indicated that the EGFR-specific uptake of the targeted CET MAb-DOCT-γ-PGA Nps was more efficient than that of the nontargeted DOCT-γ-PGA Nps by MKN-28 cells, thereby arresting the cells in the G2/M phase, disturbing the process of cell division, and further progressing the cancer cells into the death phase.…”

Section: Discussionmentioning

confidence: 99%

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

Sreeranganathan

Uthaman

Sarmento

et al. 2017

IJN

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide–N-Hydoxysuccinimide (EDC–NSH) chemistry. Increased uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of free DOCT in Swiss albino mice, indicating the possibility of improved therapeutic effect in the disease model. Qualitative in vivo imaging showed early and enhanced tumor targeted accumulation of CET MAb-DOCT-γ-PGA Nps in EGFR +ve MKN-28–based gastric cancer xenograft, which exhibited efficient arrest of tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted CET MAb-DOCT-γ-PGA Nps could be developed as a substitute to conventional nonspecific chemotherapy, and hence could become a feasible strategy for cancer therapy for EGFR-overexpressing gastric tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

Sreeranganathan

Uthaman

Sarmento

et al. 2017

IJN

View full text Add to dashboard Cite

show abstract

“…cancers) [18, 44] and cardiovascular diseases [45]. The major part of the IV injected tracers gets rapidly eliminated from the blood stream by mononuclear phagocytizing macrophages in the reticuloendothelial (RES) system [46].…”

Section: Resultsmentioning

confidence: 99%

In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents

Arami¹,

Khandhar²,

Tomitaka³

et al. 2015

Biomaterials

Self Cite

View full text Add to dashboard Cite

Magnetic Particle Imaging (MPI) is a novel non-invasive biomedical imaging modality that uses safe magnetite nanoparticles as tracers. Controlled synthesis of iron oxide nanoparticles (NPs) with tuned size-dependent magnetic relaxation properties is critical for the development of MPI. Additional functionalization of these NPs for other imaging modalities (e.g. MRI and fluorescent imaging) would accelerate screening of the MPI tracers based on their in vitro and in vivo performance in pre-clinical trials. Here, we conjugated two different types of poly-ethylene-glycols (NH2-PEG-NH2 and NH2-PEG FMOC) to monodisperse carboxylated 19.7nm NPs by amide bonding. Further, we labeled these NPs with Cy5.5 near infra-red fluorescent (NIRF) molecules. Bi-functional PEG (NH2-PEG-NH2) resulted in larger hydrodynamic size (~98nm vs. ~43nm) of the tracers, due to interparticle crosslinking. Formation of such clusters impacted the multimodal imaging performance and pharmacokinetics of these tracers. We found that MPI signal intensity of the tracers in blood depends on their plasmatic clearance pharmacokinetics. Whole body mice MPI/MRI/NIRF, used to study the biodistribution of the injected NPs, showed primary distribution in liver and spleen. Biodistribution of tracers and their clearance pathway was further confirmed by MPI and NIRF signals from the excised organs where the Cy5.5 labeling enabled detailed anatomical mapping of the tracers.in tissue sections. These multimodal MPI tracers, combining the strengths of each imaging modality (e.g. resolution, tracer sensitivity and clinical use feasibility) pave the way for various in vitro and in vivo MPI applications.

show abstract

“…It is known that receptor crosslinking can lead to internalization and localization to lysosomes in some cases such as when the anti-Her2 antibody trastuzumab is hyper-crosslinked [44]. Iron oxide nanoparticles targeted to CD20 have shown internalization in undifferentiated lymphoma B lymphocytes (MC116 cells) [45]. The pair-correlation function at 6 h (Fig.…”

Section: Resultsmentioning

confidence: 99%

Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM

Hartley

Zhang

Gudheti

et al. 2016

Journal of Controlled Release

View full text Add to dashboard Cite

We used a single-molecule localization technique called direct stochastic optical reconstruction microscopy (dSTORM) to quantify both colocalization and spatial distribution on a cellular level for two conceptually different N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. Microscopy images were acquired of entire cells with resolutions as high as 25 nm revealing the nanoscale distribution of the fluorescently labeled therapeutic components. Drug-free macromolecular therapeutics consisting of two self-assembling nanoconjugates showed slight increase in nanoclusters on the cell surface with time. Additionally, dSTORM provided high resolution images of the nanoscale organization of the self-assembling conjugates at the interface between two cells. A conjugate designed for treating ovarian cancer showed that the model drug (Cy3) and polymer bound to Cy5 were colocalized at an early time point before the model drug was enzymatically cleaved from the polymer. Using spatial descriptive statistics it was found that the drug was randomly distributed after 24 h while the polymer bound dye remained in clusters. Four different fluorescent dyes were used and two different therapeutic systems were tested to demonstrate the versatility and possible general applicability of dSTORM for use in studying drug delivery systems.

show abstract

Targeted Cell Uptake of a Noninternalizing Antibody Through Conjugation to Iron Oxide Nanoparticles in Primary Central Nervous System Lymphoma

Cited by 25 publications

References 50 publications

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents

Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM

Contact Info

Product

Resources

About

Targeted Cell Uptake of a Noninternalizing Antibody Through Conjugation to Iron Oxide Nanoparticles in Primary Central Nervous System Lymphoma

Cited by 25 publications

References 50 publications

In vivo evaluation of cetuximab-conjugated poly(&gamma;-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

In vivo evaluation of cetuximab-conjugated poly(&gamma;-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents

Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM

Contact Info

Product

Resources

About

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts