Low-Density Lipoprotein Reconstituted by Pyropheophorbide Cholesteryl Oleate as Target-Specific Photosensitizer

Zheng, Gang; Li, Hui; Zhang, Min; Lund‐Katz, Sissel; Chance, Britton; Glickson, Jerry D.

doi:10.1021/bc025516h

Cited by 101 publications

(92 citation statements)

References 14 publications

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“…As noted above, the LBNPs have been used for delivery of near-infrared f luorophores (35,53,54), photodynamic therapy agents (32,34), MRI agents (ref. 55; I. Corbin, H.L., J.C., J.D.G., and G.Z., unpublished data), and PET͞SPECT agents (18,21) to tumor cells that overexpress LDLR, and their binding was monitored by noninvasive imaging methods.…”

Section: Mechanism Underlying Selective Alkylation Of Lys -Amino Groupsmentioning

confidence: 99%

Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents

Zheng

Chen²,

Li³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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202

186

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We report that a lipoprotein-based nanoplatform generated by conjugating tumor-homing molecules to the protein components of naturally occurring lipoproteins reroutes them from their normal lipoprotein receptors to other selected cancer-associated receptors. Multiple copies of these targeting moieties may be attached to the same nanoparticle, or a variety of different targeting moieties can be attached. Such a diverse set of tumor-homing molecules could be used to create a variety of conjugated lipoproteins as multifunctional, biocompatible nanoplatforms with a broad application to both cancer imaging and treatment. The same principle can be applied to imaging and treatment of other diseases and for monitoring specific tissues. To validate this concept, we prepared a low-density lipoprotein (LDL)-based folate receptor (FR)-targeted agent by conjugating folic acid to the Lys residues of the apolipoprotein B (apoB)-100 protein. To demonstrate the ability of the lipoprotein-based nanoplatform to deliver surfaceloaded and core-loaded payloads, the particles were labeled either with the optical reporter 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine that was intercalated in the phospholipid monolayer or with the lipophilic photodynamic therapy agent, tetra-tbutyl-silicon phthalocyanine bisoleate, that was reconstituted into the lipid core. Cellular localization of the labeled LDL was monitored by confocal microscopy and flow cytometry in FR-overexpressing KB cells, in FR-nonexpressing CHO and HT-1080 cells, and in LDL receptor-overexpressing HepG 2 cells. These studies demonstrate that the folic acid conjugation to the Lys side-chain amino groups blocks binding to the normal LDL receptor and reroutes the resulting conjugate to cancer cells through their FRs.folate receptor ͉ low-density lipoprotein receptor ͉ biocompatible ͉ optical imaging ͉ photodynamic therapy

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Section: Mechanism Underlying Selective Alkylation Of Lys -Amino Groupsmentioning

confidence: 99%

Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents

Zheng

Chen²,

Li³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

202

186

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“…The sterol ester moiety is not required as modified triglycerides and fatty acids have been loaded into LDL. Furthermore, numerous contrast agent analogs containing either unsaturated fatty acyl chains or sterol ester moieties have also been successfully reconstituted into the LDL core [41,55,56]. To date, the core extraction/reconstitution procedure has only been reported for LDL in the literature.…”

Section: Core-loading "Reconstitution" Proceduresmentioning

confidence: 99%

Lipoprotein‐Based Nanoplatforms for Cancer Molecular Imaging

Corbin

Zheng

2011

Nanoplatform‐Based Molecular Imaging

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LIPOPROTEINS: NATURE'S ENDOGENOUS NANOCARRIEREfficient transport of key lipids, such as triacylglycerols (TAGs) and cholesterol, is an essential process in mammalian systems. These molecules respectively serve as a high-energy fuel source and as a structural building block for all cells. Like other essential nutrients and substrates these molecules must be delivered to cells through the blood. The hydrophobicity of these molecules, however, poses a daunting problem for their transport through the aqueous channels of the vascular system. Nature has uniquely addressed this dilemma through the lipoprotein carrier system. Plasma lipoproteins are macromolecular vehicles that transport neutral lipids (fat and cholesterol) through the circulatory system and extracellular fluid compartments of the body. These spherical emulsion-like complexes display a range of physicochemical properties; however, they have a common structural organization ( Fig. 18.1.) consisting of an apolar core of TAG and cholesterol esters surrounded by a monolayer of phospholipids and free cholesterol. Interspersed across the phospholipid monolayer are specific amphipathic proteins (apolipoproteins) whose hydrophilic domains extend toward the aqueous environment. These apolipoproteins act to stabilize and confer structural framework to the lipoproteins, modulate enzyme activity, as well as serve as receptor ligands for the lipoprotein delivery system [1]. Nanoplatform-Based Molecular Imaging Edited by Xiaoyuan ChenPlasma lipoproteins can be designated into various classes based on numerous physical parameters (e.g., electrophoretic mobility, diameter). The most commonly accepted classification is based on the density of the different lipoprotein species (see Table 18.1). According to this classification scheme the major density categories include the following.(1) Chylomicrons (d < 0.95 g/mL) are TAG-rich emulsions particles (80-88% by weight) that are synthesized by the intestine after a fatty meal. Chylomicrons are the largest particles in the lipoprotein family (80 nm to 1 m in diameter) and have the highest lipid-to-protein ratio.(2) Very low density lipoproteins (d = 0.95-1.006 g/mL) are also TAG-rich particles, however, they are synthesized by the liver. They are smaller than chylomicrons (30-80 nm in diameter) and contain relatively less TAG but more cholesterol and protein.(3) Low density lipoproteins (d = 1.020-1.063 g/mL) are particles formed from the intravascular catabolism of VLDLs. The LDL core is predominantly cholesterol ester molecules. Finally, (4) high density lipoproteins (d = 1.063-1.210 g/mL) These carriers are the smallest (6-12 nm in diameter) member of the lipoprotein family. Their core is mainly composed of cholesterol esters and they are composed of a relatively high proportion of protein (35-56% by weight).

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“…Zheng et al [82] reported a pyro-pheophorbide cholesterol oleate conjugate to target tumors overexpressing low-density lipoprotein receptors (LDLr). Pyro-pheophorbide (103) was covalently linked to 5-androsten-17b-amino-3b-ol (106) through the primary 17b-amine group to yield conjugate 107.…”

Section: Steroid-pheophorbide a Conjugatesmentioning

confidence: 99%

Steroid-photosensitizer conjugates: Syntheses and applications

Osati

Ali

Guérin

et al. 2017

J. Porphyrins Phthalocyanines

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This review focuses on progress in the development of different approaches to the design of steroid ([Formula: see text] estrogens, androgens, cholesterol) conjugates with coordination assemblies of metalloporphyrins, phthalocyanines and related complexes. Porphyrins and phthalocyanines have received considerable attention due to their novel composition, intriguing spectroscopic, photophysical, and redox properties, and potential application in light-harvesting and optoelectronic devices. With the development of more efficient imaging and therapeutic applications, these bio-conjugates are evaluated as multimodality agents (PET, fluorescence imaging) to monitor the mechanism of action of biologically active components in living systems and as agents for molecular recognition, oxygen atom transfer and catalysis. The tetrapyrrole components, which can be coupled via covalent and various non-covalent linkages, may exhibit strong interactions through efficient photo-induced electron and/or energy transfer processes.

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Low-Density Lipoprotein Reconstituted by Pyropheophorbide Cholesteryl Oleate as Target-Specific Photosensitizer

Cited by 101 publications

References 14 publications

Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents

Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents

Lipoprotein‐Based Nanoplatforms for Cancer Molecular Imaging

Steroid-photosensitizer conjugates: Syntheses and applications

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