Molecular Targeting of Drug Delivery Systems to Cancer

Minko, Tamara; Dharap, S.; Pakunlu, Refika I.; Wang, Y.

doi:10.2174/1389450043345443

Cited by 167 publications

(119 citation statements)

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“…LHRH peptide is a ligand for the receptors that are overexpressed in plasma membrane of breast, ovarian, and prostate cancer cells [26,29,37] and, as found in the present study, in some types of lung cancer cells. In contrast, the expression of these receptors in healthy organs in most cases is non-detectable [23,38].…”

Section: Discussionsupporting

confidence: 82%

Receptor targeted polymers, dendrimers, liposomes: Which nanocarrier is the most efficient for tumor-specific treatment and imaging?

Saad

Garbuzenko

Ber

et al. 2008

Journal of Controlled Release

222

165

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To compare the influence of different characteristics of nanocarriers on the efficacy of chemotherapy and imaging, we designed, characterized, and evaluated three widely used nanocarriers: linear polymer, dendrimer and liposome in vitro and in vivo. These nanocarriers delivered the same anticancer drug (paclitaxel) and/or imaging agent (Cy5.5). A synthetic analog of LHRH peptide targeted to receptors overexpressed on the membrane of cancer cells was attached to the nanocarriers as a tumor targeting moiety. Significant differences were found between various studied non-targeted carriers in their cellular internalization, cytotoxicity, tumor and organ distribution and anticancer efficacy. LHRH peptide substantially enhanced intratumoral accumulation and anticancer efficacy of all delivery systems and minimized their adverse side effects. For the first time, the present study revealed that the targeting of nanocarriers to tumorspecific receptors minimizes the influence of the architecture, composition, size and molecular mass of nanocarriers on the efficacy of imaging and cancer treatment.

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Section: Discussionsupporting

confidence: 82%

Receptor targeted polymers, dendrimers, liposomes: Which nanocarrier is the most efficient for tumor-specific treatment and imaging?

Saad

Garbuzenko

Ber

et al. 2008

Journal of Controlled Release

222

165

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“…Overexpression of the luteinizing hormone-releasing hormone (LHRH) receptor has been reported in breast, ovarian, and prostate cancer cells, [16][17][18][19] whereas no detectable expression of LHRH receptors has been observed in most visceral organs. Previous reports by Dharap et al 17,20 and Tang et al 19 demonstrated that LHRH peptide could be used as a targeting moiety on drug-delivery systems to enhance drug uptake by breast, ovarian, and prostate cancer cells, and reduce the relative availability of the toxic drug to normal cells.…”

Section: Liu Et Almentioning

confidence: 99%

TAT-LHRH conjugated low molecular weight chitosan as a gene carrier specific for hepatocellular carcinoma cells

Liu¹,

Dong²,

Zhu³

et al. 2014

IJN

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To develop a chitosan-based nonviral gene carrier capable of delivering genes specifically into hepatoma cells, a bifunctional peptide composed of the TAT (transactivator of transcription) peptide and luteinizing hormone-releasing hormone (LHRH) was conjugated with low molecular weight chitosan, resulting in a TAT-LHRH-chitosan conjugate (TLC). TLC/DNA nanoparticles (TLCDNPs) were characterized by agarose gel retardation, atomic force microscopy, and dynamic light scattering analysis. In vitro targeting specificity and transfection efficiency were analyzed with a GE IN Cell Analyzer 2000 High-Content Cellular Analysis System. The results demonstrated that TLC had stronger DNA condensing power than unmodified chitosan, and that TLCDNPs were of roughly round shape with average diameter of 70–85 nm and zeta potential of +30 mV and were relatively stable in solution. The in vitro study demonstrated TLC was highly selective for hepatoma cells and essentially nontoxic.

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“…Tumor targeting of a cytotoxic agent refers to the passive accumulation of nano-scaled drug carriers to solid tumors, followed by active internalization into tumor cells [1]. The internalization of drug, either alone or along with a carrier, is required for cell death because most cytotoxic drugs act intracellularly [2,3].…”

Section: Introductionmentioning

confidence: 99%

TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors

Sethuraman

Bae

2007

Journal of Controlled Release

318

205

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A novel drug targeting system for acidic solid tumors has been developed based on ultra pH sensitive polymer and cell penetrating TAT. The delivery system consisted of two components: 1) A polymeric micelle that has a hydrophobic core made of Poly(L-lactic acid) (PLLA) and a hydrophilic shell consisting of Polyethylene Glycol (PEG) conjugated to TAT (TATmicelle), 2) An ultra pH sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and PEG (PSD-b-PEG). The anionic PSD is complexed with cationic TAT of the micelles to achieve the final carrier, which could systemically shield the micelles and expose them at slightly acidic tumor pH. TATmicelles had particle sizes between 20 to 45 nm and their critical micelle concentrations were 3.5 mg/L to 5.5 mg/ L. The TATmicelles, upon mixing with pH sensitive PSD-b-PEG, showed slight increase in particle size between pH 8.0 and 6.8 (60-90 nm), indicating complexation. As the pH was decreased (pH 6.6 to 6.0) two populations were observed, one that of normal TAT micelles (45 nm) and the other of aggregated hydrophobic PSD-b-PEG. Zeta potential measurements showed similar trend substantiating the shielding/deshielding process. Flowcytometry and confocal microscopy showed significantly higher uptake of TAT micelles at pH 6.6 compared to pH 7.4 indicating shielding at normal pH and deshielding at tumor pH. The flowcytometry indicated that the TAT not only translocates into the cells but is also seen on the surface of the nucleus. These results strongly indicate that the above drug loaded micelles would be able to target any hydrophobic drug near the nucleus.

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Molecular Targeting of Drug Delivery Systems to Cancer

Cited by 167 publications

References 0 publications

Receptor targeted polymers, dendrimers, liposomes: Which nanocarrier is the most efficient for tumor-specific treatment and imaging?

Receptor targeted polymers, dendrimers, liposomes: Which nanocarrier is the most efficient for tumor-specific treatment and imaging?

TAT-LHRH conjugated low molecular weight chitosan as a gene carrier specific for hepatocellular carcinoma cells

TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors

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