Solubilization of flurbiprofen into aptamer-modified PEG–PLA micelles for targeted delivery to brain-derived endothelial cells<i>in vitro</i>

Mu, Chaofeng; Dave, Nimita; Hu, Jing; Desai, Pankaj B.; Pauletti, Giovanni M.; Bai, Shuhua; Hao, Jiukuan

doi:10.3109/02652048.2013.778907

Cited by 29 publications

(15 citation statements)

References 34 publications

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“…An aptamer-conjugated PEG-PLA micelle was recently designed for specific delivery to the brain [145]. In this study, the transferrin receptor aptamer selected by was exploited for its ability to activate receptor mediated transcytosis, effectively delivering the flurbiprofen-loaded micelles across a murine cellular model of the BBB (bEND5 cells) [143].…”

Section: Aptamers For Transferrin Receptorsmentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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Oligonucleotide aptamers are short, synthetic, single-stranded DNA or RNA able to recognize and bind to a multitude of targets ranging from small molecules to cells. Aptamers have emerged as valuable tools for fundamental research, clinical diagnosis, and therapy. Due to their small size, strong target affinity, lack of immunogenicity, and ease of chemical modification, aptamers are an attractive alternative to other molecular recognition elements, such as antibodies. Although it is a challenging environment, the central nervous system and related molecular targets present an exciting potential area for aptamer research. Aptamers hold promise for targeted drug delivery, diagnostics, and therapeutics. Here we review recent advances in aptamer research for neurotransmitter and neurotoxin targets, demyelinating disease and spinal cord injury, cerebrovascular disorders, pathologies related to protein aggregation (Alzheimer's, Parkinson's, and prions), brain cancer (glioblastomas and gliomas), and regulation of receptor function. Challenges and limitations posed by the blood brain barrier are described. Future perspectives for the application of aptamers to the central nervous system are also discussed.

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Section: Aptamers For Transferrin Receptorsmentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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“…Recently, a published anti-MUC1 (mucin1) DNA aptamer 66 was used to covalently construct a DNA aptamer-miRNA chimera. 67 Mucin1, a cell surface glycoprotein, is overexpressed and glycosylated on the cell surface of a majority of human adenocarcinomas.…”

Section: Cell-specific Aptamer-functionalized Agentsmentioning

confidence: 99%

“…66 developed aptamer-functionalized PEG-polylactic acid (PEG-PLA) micelles (APP) designed to target the TfR on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer's disease, was encapsulated into APP micelles through a cosolvent evaporation method.…”

Section: Cell-specific Aptamer-functionalized Agentsmentioning

confidence: 99%

Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

Zhou

Rossi

2014

Molecular Therapy - Nucleic Acids

207

162

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One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges.

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“…Accumulation of flurbiprofen in target cells, binding activity and intracellular uptake of micelle were also confirmed in vitro. However, the study is lacking in vivo data [114]. …”

Section: Aptamer-nanoparticles Systemsmentioning

confidence: 99%

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

2016

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The selective delivery of drugs in a cell- or tissue-specific manner represents the main challenge for medical research; in order to reduce the occurrence of unwanted off-target effects. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules due to their ability to bind with high affinity to specific ligands; their high chemical flexibility; as well as tissue penetration capability. To date, different aptamer-drug systems and aptamer–nanoparticles systems, in which nanoparticles function together with aptamers for the targeted delivery, have been successfully developed for a wide range of therapeutics, including toxins; peptides; chemotherapeutics and oligonucleotides. Therefore, aptamer-mediated drug delivery represents a powerful tool for the safe and effective treatment of different human pathologies, including cancer; neurological diseases; immunological diseases and so on. In this review, we will summarize recent progress in the field of aptamer-mediated drug delivery and we will discuss the advantages, the achieved objectives and the challenges to be still addressed in the near future, in order to improve the effectiveness of therapies.

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Solubilization of flurbiprofen into aptamer-modified PEG–PLA micelles for targeted delivery to brain-derived endothelial cellsin vitro

Cited by 29 publications

References 34 publications

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

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