Folate Receptor Targeted Delivery of Polyelectrolyte Complex Micelles Prepared from ODN-PEG-Folate Conjugate and Cationic Lipids

2007 ◽  
Vol 23 (1) ◽  
pp. 232-237 ◽  
Author(s):  
S.H. Kim ◽  
J.H. Jeong ◽  
H. Mok ◽  
S.H. Lee ◽  
S.W. Kim ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Polyelectrolyte Complex ◽  
Folate Receptor ◽  
Cationic Lipids ◽  
Folate Conjugate ◽  
Complex Micelles

Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA–PEG–folate conjugate

2008 ◽  
Vol 16 (5) ◽  
pp. 415-423 ◽  
Author(s):  
Farnaz Esmaeili ◽  
Mohammad Hossein Ghahremani ◽  
Seyed Nasser Ostad ◽  
Fatemeh Atyabi ◽  
Mohammad Seyedabadi ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Folate Receptor ◽  
Folate Conjugate

scholarly journals Protein–Polyelectrolyte Complexes and Micellar Assemblies

Polymers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1097 ◽  
Author(s):  
Gao ◽  
Holkar ◽  
Srivastava
Keyword(s):  
Self Assembly ◽  
Targeted Delivery ◽  
Electrostatic Interactions ◽  
Recent Progress ◽  
Polyelectrolyte Complex ◽  
Patchy Distribution ◽  
Polyelectrolyte Complexes ◽  
Wrong Side ◽  
Complex Micelles ◽  
Structure Properties

In this review, we highlight the recent progress in our understanding of the structure, properties and applications of protein–polyelectrolyte complexes in both bulk and micellar assemblies. Protein–polyelectrolyte complexes form the basis of the genetic code, enable facile protein purification, and have emerged as enterprising candidates for simulating protocellular environments and as efficient enzymatic bioreactors. Such complexes undergo self-assembly in bulk due to a combined influence of electrostatic interactions and entropy gains from counterion release. Diversifying the self-assembly by incorporation of block polyelectrolytes has further enabled fabrication of protein–polyelectrolyte complex micelles that are multifunctional carriers for therapeutic targeted delivery of proteins such as enzymes and antibodies. We discuss research efforts focused on the structure, properties and applications of protein–polyelectrolyte complexes in both bulk and micellar assemblies, along with the influences of amphoteric nature of proteins accompanying patchy distribution of charges leading to unique phenomena including multiple complexation windows and complexation on the wrong side of the isoelectric point.

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Large Scale ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Target Cells ◽  
Scale Production ◽  
Stepwise Development ◽  
Chimeric Peptides

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.

scholarly journals Onco-Receptors Targeting in Lung Cancer via Application of Surface-Modified and Hybrid Nanoparticles: A Cross-Disciplinary Review

Processes ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 621
Author(s):  
Fakhara Sabir ◽  
Maimoona Qindeel ◽  
Mahira Zeeshan ◽  
Qurrat Ul Ain ◽  
Abbas Rahdar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Delivery ◽  
Current Knowledge ◽  
Folate Receptor ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
The Body ◽  
Hybrid Nanoparticles ◽  
Wide Range ◽  
Surface Modified

Lung cancer is among the most prevalent and leading causes of death worldwide. The major reason for high mortality is the late diagnosis of the disease, and in most cases, lung cancer is diagnosed at fourth stage in which the cancer has metastasized to almost all vital organs. The other reason for higher mortality is the uptake of the chemotherapeutic agents by the healthy cells, which in turn increases the chances of cytotoxicity to the healthy body cells. The complex pathophysiology of lung cancer provides various pathways to target the cancerous cells. In this regard, upregulated onco-receptors on the cell surface of tumor including epidermal growth factor receptor (EGFR), integrins, transferrin receptor (TFR), folate receptor (FR), cluster of differentiation 44 (CD44) receptor, etc. could be exploited for the inhibition of pathways and tumor-specific drug targeting. Further, cancer borne immunological targets like T-lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and dendritic cells could serve as a target site to modulate tumor activity through targeting various surface-expressed receptors or interfering with immune cell-specific pathways. Hence, novel approaches are required for both the diagnosis and treatment of lung cancers. In this context, several researchers have employed various targeted delivery approaches to overcome the problems allied with the conventional diagnosis of and therapy methods used against lung cancer. Nanoparticles are cell nonspecific in biological systems, and may cause unwanted deleterious effects in the body. Therefore, nanodrug delivery systems (NDDSs) need further advancement to overcome the problem of toxicity in the treatment of lung cancer. Moreover, the route of nanomedicines’ delivery to lungs plays a vital role in localizing the drug concentration to target the lung cancer. Surface-modified nanoparticles and hybrid nanoparticles have a wide range of applications in the field of theranostics. This cross-disciplinary review summarizes the current knowledge of the pathways implicated in the different classes of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. Furthermore, it focuses specifically on the significance and emerging role of surface functionalized and hybrid nanomaterials as drug delivery systems through citing recent examples targeted at lung cancer treatment.

scholarly journals Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 424 ◽  
Author(s):  
Klaudia Siwowska ◽  
Patrycja Guzik ◽  
Katharina A. Domnanich ◽  
Josep M. Monné Rodríguez ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Potential ◽  
Folate Receptor ◽  
Tumor Growth Inhibition ◽  
Therapeutic Effects ◽  
Targeted Radionuclide Therapy ◽  
Decay Properties ◽  
Therapeutic Properties ◽  
Folate Conjugate

Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy β−-particles. In this study, 47Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of 177Lu-folate and 90Y-folate, respectively. In vitro, 47Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to 177Lu-folate, but 90Y-folate was more potent at equal activities due to the higher energy of emitted β−-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5 MBq), 177Lu-folate (10 MBq), and 90Y-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, 47Sc is likely to be comparable to 177Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with 44Sc or 43Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.

scholarly journals Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2553
Author(s):  
Jeffrey M. Ting ◽  
Alexander E. Marras ◽  
Joseph D. Mitchell ◽  
Trinity R. Campagna ◽  
Matthew V. Tirrell
Keyword(s):  
Ethylene Glycol ◽  
Polyelectrolyte Complex ◽  
Serum Proteins ◽  
Raft Polymerization ◽  
Sodium Acrylate ◽  
Structure Property ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene ◽  
Complex Micelles

A series of model polyelectrolyte complex micelles (PCMs) was prepared to investigate the consequences of neutral and zwitterionic chemistries and distinct charged cores on the size and stability of nanocarriers. Using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization, we synthesized a well-defined diblock polyelectrolyte system, poly(2-methacryloyloxyethyl phosphorylcholine methacrylate)-block-poly((vinylbenzyl) trimethylammonium) (PMPC-PVBTMA), at various neutral and charged block lengths to compare directly against PCM structure–property relationships centered on poly(ethylene glycol)-block-poly((vinylbenzyl) trimethylammonium) (PEG-PVBTMA) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLK). After complexation with a common polyanion, poly(sodium acrylate), the resulting PCMs were characterized by dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). We observed uniform assemblies of spherical micelles with a diameter ~1.5–2× larger when PMPC-PVBTMA was used compared to PEG-PLK and PEG-PVBTMA via SAXS and DLS. In addition, PEG-PLK PCMs proved most resistant to dissolution by both monovalent and divalent salt, followed by PEG-PVBTMA then PMPC-PVBTMA. All micelle systems were serum stable in 100% fetal bovine serum over the course of 8 h by time-resolved DLS, demonstrating minimal interactions with serum proteins and potential as in vivo drug delivery vehicles. This thorough study of the synthesis, assembly, and characterization of zwitterionic polymers in PCMs advances the design space for charge-driven micelle assemblies.

scholarly journals The Development of Functional Non-Viral Vectors for Gene Delivery

2019 ◽  
Vol 20 (21) ◽  
pp. 5491 ◽  
Author(s):  
Patil ◽  
Gao ◽  
Lin ◽  
Li ◽  
Dang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
High Efficiency ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Gene Vectors ◽  
Potential Applications ◽  
Low Toxicity ◽  
Low Cytotoxicity

Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.

scholarly journals Polymerized Selenium Nanoparticles for Folate-Receptor-Targeted Delivery of Anti-Luc-siRNA: Potential for Gene Silencing

Biomedicines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 76 ◽  
Author(s):  
Fiona Maiyo ◽  
Moganavelli Singh
Keyword(s):  
Gene Silencing ◽  
Cell Lines ◽  
Targeted Delivery ◽  
Folate Receptor ◽  
Docking Studies ◽  
Selenium Nanoparticles ◽  
Luciferase Gene ◽  
Therapeutic Outcomes ◽  
Transmission Electron

The development of a biocompatible and nontoxic gene delivery vehicle remains a challenging task. Selenium nanoparticles (SeNPs) have the potential to increase delivery efficiency, to reduce side effects, and to improve therapeutic outcomes. In this study, chitosan (Ch) functionalized folate (FA)-targeted SeNPs were synthesized, characterized, and evaluated for their potential to bind, protect, and safely deliver Fluc-siRNA in vitro. SeNPs of less than 100 nm were successfully synthesised and further confirmed using UV-vis and Fourier transform infrared spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. Cell viability studies were conducted in vitro in selected cancer and non-cancer cell lines. Folate receptor (FOLR1) targeted and nontargeted luciferase gene silencing studies were assessed in the transformed Hela-tat-Luc cell line expressing the luciferase gene. Targeted and nontargeted SeNP nanocomplexes showed minimal toxicity in all cell lines at selected w/w ratios. Maximum gene silencing was achieved at optimum w/w ratios for both nanocomplexes, with Selenium-chitosan-folic acid (SeChFA) nanocomplexes showing slightly better transgene silencing, as supported by results from docking studies showing that SeChFA nanocomplexes interacted strongly with the folate receptor (FOLR1) with high binding energy of −4.4 kcal mol−1.

scholarly journals Structure–Property Relationships of Oligonucleotide Polyelectrolyte Complex Micelles

Nano Letters ◽  
2018 ◽  
Vol 18 (11) ◽  
pp. 7111-7117 ◽  
Author(s):  
Michael Lueckheide ◽  
Jeffrey R. Vieregg ◽  
Alex J. Bologna ◽  
Lorraine Leon ◽  
Matthew V. Tirrell
Keyword(s):  
Polyelectrolyte Complex ◽  
Structure Property ◽  
Structure Property Relationships ◽  
Complex Micelles
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