The transcription factor nuclear factor-κB (NF-κB) is a critical regulator of the immune response, inflammation, cell growth, and survival. Canonical and non-canonical pathways, two NF-κB pathways, are activated through diverse stimulators and receptors. NF-κB activity is dysregulated in various inflammation-related diseases and cancers. It was found that the persistent NF-κB activity has a major role in proliferation, apoptosis inhibition, metastasis, and cell cycle disruption in cancer cells and also the survival of cancer stem cells (CSCs) within the tumors. Therefore, suppression of the NF-κB pathway could be a promising therapeutic target for cancer therapy. Different biological inhibitors (e.g., peptides, small molecules, antisense oligonucleotides (ASOs), and antibodies (Abs)) have been demonstrated to inhibit the NF-κB pathway. Low stability in the circulation system, weak availability, and poor cellular uptake of some inhibitors limit their therapeutic applications. To address these drawbacks nanocarrier systems are often formulated and applied in drug delivery as an effective therapeutic approach. Targeted nanosystems (i.e., small molecules, peptides, Abs and Aptamers (Aps) conjugated nanocarriers), as well as smart responsive nanocarriers, can improve the efficiency of therapeutics while reducing the off-target toxicity. This review describes the NF-κB signaling pathways and mechanisms of their over-activation in tumor initiation and progression. The NF-κB inhibitors and their clinical applications are also discussed. It also overviews different nanocarriers used as robust vehicles for the delivery of NF-κB inhibitors and anti-tumor agents to improve the bioavailability of drugs and selective targeting of cancer cells to repress NF-κB activity in tumor cells. 

Engineered nanoparticles as emerging gene/drug delivery systems targeting the nuclear factor-κB protein and related signaling pathways in cancer.

The delivery and binding of the therapeutic molecules like drugs, siRNAs and toxins to their specific target is a challenging task. Poor efficacy and off target binding are major problems associated with current approaches for targeted delivery of therapeutic molecules. Therefore, to avoid off target binding, target specific delivery systems are urgently required. Over the years, aptamers have become attractive molecules for targeted delivery of drugs. Aptamers are defined as small, single-stranded DNA/RNA or peptides which can bind to the specific targets with better affinity. The therapeutic molecules can either conjugate directly to the aptamers or along with some carrier molecules like liposomes, antibodies and nanoparticles to achieve specific targeted delivery. The present book chapter will focus on aptamer mediated target specific delivery of drugs, toxins and siRNAs- both direct conjugation with aptamer and in association with carriers.

Aptamer: Apt System for Target-Specific Drug Delivery

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Aptamer: Apt System for Target-Specific Drug Delivery