Biofunctionalized targeted nanoparticles for therapeutic applications

Wang, Andrew Z.; Gu, Frank; Zhang, Liangfang; Chan, Juliana M.; Radovic-Moreno, Aleksander; Shaikh, Mariam R; Farokhzad, Omid C.

doi:10.1517/14712598.8.8.1063

Cited by 235 publications

(103 citation statements)

References 61 publications

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“…Peptide ligands with smaller sizes can provide 1) a decreased possibility of affecting the function of the coupled drug, especially enzyme drugs, 2) availability of multivalency and 3) less immunogenicity [14,15] . Various peptide ligands have recently been developed due to the advancement of technologies for discovering novel peptides that can selectively bind to tumor cells, such as phage-display cDNA libraries.…”

Section: Introductionmentioning

confidence: 99%

Molecular tumor targeting of gelonin by fusion with F3 peptide

2017

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Therapeutically potent macromolecular drugs have shown great promise for overcoming the limitations of small-molecule anti-cancer drugs. But tumor cell-selective intracellular delivery of the macromolecules remains a major hurdle for their successful clinical application. To overcome this challenge, we engineered a novel genetic fusion protein (F3-Gel) that composed of F3 peptide, a tumorhoming peptide, and gelonin, a plant-derived ribosome-inactivating protein (RIP), and then evaluated its anti-cancer activity in vitro and in vivo. The F3-Gel-encoding gene was synthesized by genetic recombination, and F3-Gel was successfully expressed in E coli. The anti-cancer activity of the produced F3-Gel was evaluated by various in vitro assays, which revealed that F3-Gel maintained equipotent protein synthesis inhibition activity (IC 50 =11 pmol/L) as unmodified gelonin (IC 50 =10 pmol/L). Furthermore, F3-Gel displayed enhanced cellular uptake into cancer cells (U87 MG, HeLa, LnCaP and 9L) than noncancerous cells (293 HEK and SVGp12). Compared with gelonin, F3-Gel exerted significantly higher cytotoxicity against these cancer cells. F3-Gel displayed significantly greater inhibition of protein translation in U87 MG cells: F3-Gel (0.5 μmol/L) was able to reduce the protein level to less than 50%, while gelonin (1 μmol/L) did not affect the intracellular protein level. In a U87 MG xenograft tumor-bearing mouse model, F3-Gel was accumulated in the tumor site at much higher levels and maintained for a prolonged time compared with gelonin. Administration of F3-Gel (0.5, 0.75 mol/kg, iv) caused 36% and 66%, respectively, inhibition of tumor growth in U87 MG xenograft mice, suggesting that it is a promising candidate drug for cancer treatment. Furthermore, this study demonstrates that fusion of F3 peptide to a potent macromolecule could provides an effective method for targeting tumors and eventually could improve their druggability.

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Section: Introductionmentioning

confidence: 99%

Molecular tumor targeting of gelonin by fusion with F3 peptide

2017

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“…Over recent decades, different types of nanoparticles have been studied for their use in therapeutic applications. At present, perhaps the most interesting nanoparticles for clinical use are liposomes, 28 which are spherical vesicles surrounded by a bilayer membrane shell composed of natural or synthetic lipids. [29][30][31] The possibility of preparing both biocompatible and biodegradable compositions, together with encapsulation of either hydrophilic or hydrophobic therapeutic agents, makes liposomes excellent carriers.…”

Section: Discussionmentioning

confidence: 99%

Peptide-mediated targeting of liposomes to TrkB receptor-expressing cells

Ranjan¹,

Sood²,

Dudás³

et al. 2012

IJN

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Background:The neurotrophic receptor tyrosine kinase B (TrkB) has diverse signaling roles in neurons and tumor cells. Accordingly, its suppressive targeting is of interest in neuroblastoma and other tumors, whereas its role in improving survival is focused in neurons. Here we describe targeting of TrkB-binding peptide-conjugated liposomes (PCL) to the TrkB-expressing mouse macrophage-like cell line RAW264, and to all-trans-retinoic acid-treated neuron-like TrkB Conclusion:We demonstrate here the feasibility of targeting liposomes to TrkB-expressing cells by 18-mer peptides, promoting cellular uptake (at least partly into endosomes) via receptormediated pathways.

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“…Aptamers can be synthesized with a specific functional moiety, such as a carboxylate, amino or sulfhydryl at only one end of the nucleic acid sequence of the aptamer. They are small in size and non-immunogenic [50,53]. Peptides are an attractive alternative as targeting molecule due to several advantages, including a smaller size, a lower immunogenicity, a higher tissue penetration capability, a higher stability and a relatively easy production process.…”

Section: Targeting Ligandsmentioning

confidence: 99%

Smart multifunctional nanoparticles in nanomedicine

Şeleci

Joncyzk

et al. 2016

BioNanoMaterials

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Recent advances in nanotechnology caused a growing interest using nanomaterials in medicine to solve a number of issues associated with therapeutic agents. The fabricated nanomaterials with unique physical and chemical properties have been investigated for both diagnostic and therapeutic applications. Therapeutic agents have been combined with the nanoparticles to minimize systemic toxicity, increase their solubility, prolong the circulation half-life, reduce their immunogenicity and improve their distribution. Multifunctional nanoparticles have shown great promise in targeted imaging and therapy. In this review, we summarized the physical parameters of nanoparticles for construction of "smart" multifunctional nanoparticles and their various surface engineering strategies. Outlook and questions for the further researches were discussed.

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Biofunctionalized targeted nanoparticles for therapeutic applications

Cited by 235 publications

References 61 publications

Molecular tumor targeting of gelonin by fusion with F3 peptide

Molecular tumor targeting of gelonin by fusion with F3 peptide

Peptide-mediated targeting of liposomes to TrkB receptor-expressing cells

Smart multifunctional nanoparticles in nanomedicine

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