Faculty Opinions recommendation of Tumor-homing peptides as tools for targeted delivery of payloads to the placenta.

2016 ◽  
Author(s):  
Megan Holmes
Keyword(s):  
Targeted Delivery ◽  
Tumor Homing

scholarly journals Tumor-homing peptides as tools for targeted delivery of payloads to the placenta

2016 ◽  
Vol 2 (5) ◽  
pp. e1600349 ◽  
Author(s):  
Anna King ◽  
Cornelia Ndifon ◽  
Sylvia Lui ◽  
Kate Widdows ◽  
Venkata R. Kotamraju ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Targeted Delivery ◽  
Normal Development ◽  
Coated Nanoparticles ◽  
Mouse Placenta ◽  
Pregnant Mice ◽  
Tumor Homing ◽  
Homing Peptide ◽  
And Function ◽  
Proof Of Principle

The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics.

scholarly journals Treatment of Peritoneal Carcinomatosis by Targeted Delivery of the Radio-Labeled Tumor Homing Peptide 213Bi-DTPA-[F3]2 into the Nucleus of Tumor Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (5) ◽  
pp. e5715 ◽  
Author(s):  
Enken Drecoll ◽  
Florian C. Gaertner ◽  
Matthias Miederer ◽  
Birgit Blechert ◽  
Mario Vallon ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Tumor Homing ◽  
Homing Peptide

scholarly journals A smart viral vector for targeted delivery of hydrophobic drugs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sukanya Ghosh ◽  
Manidipa Banerjee
Keyword(s):  
Targeted Delivery ◽  
Viral Vector ◽  
Fundamental Problem ◽  
Target Cells ◽  
Immune Reactivity ◽  
Hydrophobic Drugs ◽  
Drug Release Profile ◽  
Capsid Shell ◽  
Tumor Homing ◽  
Homing Peptide

AbstractTargeted delivery of hydrophobic chemotherapeutic drugs to tumor cells remains a fundamental problem in cancer therapy. Effective encapsulation of hydrophobic drugs in nano-vehicles can improve their pharmacokinetics, bioavailability and prevent off-target localization. We have devised a method for easy chemical conjugation and multivalent display of a tumor-homing peptide to virus-like particles of a non-mammalian virus, Flock House Virus (FHV), to engineer it into a smart vehicle for targeted delivery of hydrophobic drugs. This conjugation method provides dual functionalization to the VLPs, first, a 2 kDa PEG spacer arm shields VLPs from immune reactivity, and second, attachment of the tumor homing peptide tLyP-1 chauffeurs the encapsulated hydrophobic drugs to target cells. The fortuitous affinity of the FHV capsid towards hydrophobic molecules, and dependence on Ca2+ for maintaining a stable capsid shell, were utilized for incorporation of hydrophobic drugs—doxorubicin and ellipticine—in tLyP-1 conjugated VLPs. The drug release profile from the VLP was observed to be gradual, and strictly endosomal pH dependent. We propose that this accessible platform empowers surface functionalization of VLP with numerous ligands containing terminal cysteines, for generating competent delivery vehicles, antigenic display and other biomedical applications.

scholarly journals Magnetic-Fe/Fe3O4-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages

2012 ◽  
Vol 3 ◽  
pp. 444-455 ◽  
Author(s):  
Hongwang Wang ◽  
Tej B Shrestha ◽  
Matthew T Basel ◽  
Raj Kumar Dani ◽  
Gwi-Moon Seo ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Cancer Treatment ◽  
Targeted Delivery ◽  
Topoisomerase I ◽  
Raw264.7 Cells ◽  
Cancer Site ◽  
Diameter Core ◽  
Low Toxicity ◽  
Tumor Homing ◽  
Advanced System

The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell Fe/Fe3O4 magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells. They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system.

scholarly journals Design of an Amphiphilic Poly(aspartamide)-mediated Self-assembled Nanoconstruct for Long-Term Tumor Targeting and Bioimaging

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 885 ◽  
Author(s):  
Kondareddy Cherukula ◽  
Saji Uthaman ◽  
In-Kyu Park
Keyword(s):  
Cancer Cells ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Systemic Circulation ◽  
Systemic Clearance ◽  
Tumor Endothelium ◽  
Αvβ3 Integrins ◽  
Tumor Homing

Biodegradable polymers have been developed for the targeted delivery of therapeutics to tumors. However, tumor targeting and imaging are usually limited by systemic clearance and non-specific adsorption. In this study, we used poly(amino acid) derivatives, such as poly(succinimide), to synthesize a nanomicelle-forming poly(hydroxyethylaspartamide) (PHEA, P) modified sequentially with octadecylamine, polyethylene glycol (PEG, P), and glycine (G) to design PHEA-PEG-glycine (PPG) nanoparticles (NPs). These PPG NPs were further tethered to cyclic Arg-Gly-Asp (cRGD) sequences for formulating tumor-targeting PPG-cRGD NPs, and then loaded with IR-780 dye (PPG-cRGD-IR-780) for visualizing tumor homing. cRGD cloaked in PPG NPs could bind specifically to both tumor endothelium and cancer cells overexpressing αvβ3 integrins. PPG-cRGD NPs exhibited enhanced physiological stability, cellular viability, and targeted intracellular uptake in cancer cells. In addition, PPG-cRGD NPs offered enhanced systemic circulation, leading to preferential tumor targeting and prolonged fluorescence tumor imaging for nearly 30 days. Nevertheless, non-targeted formulations demonstrated premature systemic clearance with short-term tumor imaging. Histochemical analysis showed no damage to normal organs, reaffirming the biocompatibility of PHEA polymers. Overall, our results indicated that PPG-cRGD NPs, which were manipulated to obtain optimal particle size and surface charge, and were complemented with tumor targeting, could improve the targeted and theranostic potential of therapeutic delivery.

scholarly journals Targeted Delivery of siRNA Therapeutics to Malignant Tumors

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
Qixin Leng ◽  
Martin C. Woodle ◽  
A. James Mixson
Keyword(s):  
Targeted Delivery ◽  
Malignant Tumors ◽  
Recombinant Antibody ◽  
Ligand Field ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
The Past ◽  
Tumor Homing ◽  
Rna And Dna

Over the past 20 years, a diverse group of ligands targeting surface biomarkers or receptors has been identified with several investigated to target siRNA to tumors. Many approaches to developing tumor-homing peptides, RNA and DNA aptamers, and single-chain variable fragment antibodies by using phage display, in vitro evolution, and recombinant antibody methods could not have been imagined by researchers in the 1980s. Despite these many scientific advances, there is no reason to expect that the ligand field will not continue to evolve. From development of ligands based on novel or existing biomarkers to linking ligands to drugs and gene and antisense delivery systems, several fields have coalesced to facilitate ligand-directed siRNA therapeutics. In this review, we discuss the major categories of ligand-targeted siRNA therapeutics for tumors, as well as the different strategies to identify new ligands.

scholarly journals Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

2020 ◽  
Vol 21 (7) ◽  
pp. 2536 ◽  
Author(s):  
Isabel Gessner ◽  
Ines Neundorf
Keyword(s):  
Physicochemical Properties ◽  
Targeted Delivery ◽  
Biomedical Applications ◽  
Cell Penetrating Peptides ◽  
Cationic Peptide ◽  
Physiological Conditions ◽  
Cell Penetrating ◽  
Tumor Homing ◽  
Cancer Diagnosis And Therapy ◽  
Insight Into

Based on their tunable physicochemical properties and the possibility of producing cell-specific platforms through surface modification with functional biomolecules, nanoparticles (NPs) represent highly promising tools for biomedical applications. To improve their potential under physiological conditions and to enhance their cellular uptake, combinations with cell-penetrating peptides (CPPs) represent a valuable strategy. CPPs are often cationic peptide sequences that are able to translocate across biological membranes and to carry attached cargos inside cells and have thus been recognized as versatile tools for drug delivery. Nevertheless, the conjugation of CPP to NP surfaces is dependent on many properties from both individual components, and further insight into this complex interplay is needed to allow for the fabrication of highly stable but functional vectors. Since CPPs per se are nonselective and enter nearly all cells likewise, additional decoration of NPs with homing devices, such as tumor-homing peptides, enables the design of multifunctional platforms for the targeted delivery of chemotherapeutic drugs. In this review, we have updated the recent advances in the field of CPP-NPs, focusing on synthesis strategies, elucidating the influence of different physicochemical properties, as well as their application in cancer research.

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