A5020903534- Nanoparticle-Based Drug Delivery
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Cancer therapeutics and mechanisms
- Advanced biosensing and bioanalysis techniques
- Nanoplatforms for cancer theranostics
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Research Studies
- Cancer Research and Treatments
- Axon Guidance and Neuronal Signaling
- Glioma Diagnosis and Treatment
- Advanced Biosensing Techniques and Applications
- Protein purification and stability
- Medical Imaging Techniques and Applications
- Cancer Treatment and Pharmacology
- Graphene and Nanomaterials Applications
- Microtubule and mitosis dynamics
- Lipid Membrane Structure and Behavior
- Occupational and environmental lung diseases
- Ubiquitin and proteasome pathways
- Machine Learning in Materials Science
- Protein Degradation and Inhibitors
- Virus-based gene therapy research
Hermes Microvision (United States)
2004-2023
Merrimack Pharmaceuticals (United States)
2011-2022
University of Toronto
2012
Princess Margaret Cancer Centre
2012
University Health Network
2012
University of California, San Francisco
1996-2011
Neurological Surgery
2006-2011
University of California, Davis
2010
Lawrence Berkeley National Laboratory
2008
UCSF Helen Diller Family Comprehensive Cancer Center
2008
We describe evidence for a novel mechanism of monoclonal antibody (MAb)-directed nanoparticle (immunoliposome) targeting to solid tumors in vivo. Long-circulating immunoliposomes targeted HER2 (ErbB2, Neu) were prepared by the conjugation anti-HER2 MAb fragments (Fab' or single chain Fv) liposome-grafted polyethylene glycol chains. fragment did not affect biodistribution long-circulating properties i.v.-administered liposomes. However, antibody-directed also increase tumor localization...
Liposomes (70-100 nm) of 1-palmitoyl-2-oleoylphosphatidylcholine, cholesterol, and poly(ethylene glycol) (PEG)-modified phosphatidylethanolamine (PEG-DSPE) were conjugated to Fab' fragments a humanized recombinant MAb against the extracellular domain HER2/neu create sterically stabilized immunoliposomes (anti-HER2 SL) as drug carrier targeting HER2-overexpressing cancers. Conjugation employed maleimide-terminated membrane-anchored spacers two kinds: short spacer, providing attachment close...
Abstract We previously reported the development of epidermal growth factor receptor (EGFR)–targeted immunoliposomes that bind and internalize in tumor cells which overexpress EGFR and/or mutant variant III (EGFRvIII), enabling intracellular delivery potent anticancer agents vitro. now describe vivo proof-of-concept for this approach multiple drugs EGFR-overexpressing models. Anti-EGFR were constructed modularly with Fab′ fragments cetuximab (IMC-C225), covalently linked to liposomes...
Abstract Liposome formulations of camptothecins have been actively pursued because the potential for significant pharmacologic advantages from successful drug delivery this important class anticancer drugs. We describe nanoliposomal CPT-11, a novel nanoparticle/liposome construct containing CPT-11 (irinotecan) with unprecedented loading efficiency and in vivo retention. Using modified gradient method featuring sterically hindered amine highly charged, multivalent anionic trapping agents,...
Abstract Purpose: Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR its variability human tumors is highly debated has been proposed as an explanation for variable responses therapeutic clinical studies. Experimental Design: We assessed the effect patients using a 64Cu-labeled nanoparticle, 64Cu-MM-302 (64Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), imaging by PET/CT....
We hypothesized that immunoliposomes (ILs) target epidermal growth factor receptor (EGFR) and/or its truncated variant EGFRvIII can be constructed to provide efficient intracellular drug delivery in tumor cells overexpressing these receptors. Monoclonal antibody fragments included Fab' derived from C225, which binds both EGFR and EGFRvIII, or novel anti-EGFR scFv C10, only. were covalently linked liposomes containing various reporters drugs. ILs evaluated for specific binding,...
Targeted drug delivery systems that combine imaging and therapeutic modalities in a single macromolecular construct may offer advantages the development application of nanomedicines. To incorporate unique optical properties luminescent quantum dots (QDs) into immunoliposomes for cancer diagnosis treatment, we describe synthesis, biophysical characterization, tumor cell-selective internalization, anticancer QD-conjugated immunoliposome-based nanoparticles (QD-ILs). Pharmacokinetic vivo...
Abstract Although liposomes have been used as a vehicle for delivery of therapeutic agents in oncology, their efficacy targeting brain tumors has limited due to poor penetration through the blood-brain barrier. Because convection-enhanced (CED) may improve index tumors, we conducted three-stage study: stage 1 established feasibility using vivo magnetic resonance imaging (MRI) confirm adequate liposomal distribution within targeted regions normal rat brain. Liposomes colabeled with gadolinium...
Modification of liposome surface with polyethylene glycol was used to improve oligodeoxyribonucleotide (ODN) loading, stability the resulting complexes, and specificity cellular delivery ODN by cationic liposomes. Liposomes composed a lipid (DOTAP, DOGS, DDAB), neutral (DOPE), phospholipid derivative (PEG-PE) formed complex 18-mer phosphorothioate up ODN/lipid molar ratio 0.25. The complexes showed intact vesicular structures similar original liposomes their size (100–130 nm) unchanged after...
Plasma-stable liposomes (100 nm) were prepared from dioleoylphosphatidylethanolamine (DOPE) and 3-6 mol% of a new disulfide-linked poly(ethylene glycol)-phospholipid conjugate (mPEG-DTP-DSPE). In contrast to similar preparations containing non-cleavable PEG-phospholipid conjugate, thiolytic cleavage the grafted polymer chains facilitated rapid complete release liposome contents. Furthermore, detachment PEG DOPE resulted in liposomal fusion. Finally, while formulation pH-sensitive...
Abstract We hypothesized that combining convection-enhanced delivery (CED) with a novel, highly stable nanoparticle/liposome containing CPT-11 (nanoliposomal CPT-11) would provide dual drug strategy for brain tumor treatment. Following CED in rat brains, tissue retention of nanoliposomal was greatly prolonged, >20% injected dose remaining at 12 days all doses. Tissue residence dependent, doses 60 μg (3 mg/mL), 0.8 mg (40 and 1.6 (80 mg/mL) resulting half-life (t1/2) 6.7, 10.7, 19.7...
We have previously shown that convection-enhanced delivery (CED) of highly stable nanoparticle/liposome agents encapsulating chemotherapeutic drugs is effective against intracranial rodent brain tumor xenografts. In this study, we evaluated the combination a newly developed containing topoisomerase I inhibitor CPT-11 (nanoliposomal [nLs-CPT-11]), and PEGylated liposomal doxorubicin (Doxil) II doxorubicin. Both were detectable in CNS for more than 36 days after single CED application. Tissue...
Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas investigate use convection-enhanced delivery (CED) liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization intratumoral infusions by real-time magnetic...