Improved Targeting and Safety of Doxorubicin through a Novel Albumin Binding Prodrug Approach.

Human serum albumin (HSA) improves the pharmacokinetic profile of drugs attached to it, making it an attractive carrier with proven clinical success. In our previous studies, we have shown that Caveolin-1 (Cav-1) and caveolae-mediated endocytosis play important roles in the uptake of HSA and albumin-bound drugs. Doxorubicin is an FDA-approved chemotherapeutic agent that is effective against multiple cancers, but its clinical applicability has been hampered by its high toxicity levels.

Antitumor Activity of Anti-miR-21 Delivered through Lipid Nanoparticles.

The ability of lipid nanoparticles (LNPs) to deliver nucleic acids have shown a great therapeutic potential to treat a variety of diseases. Here, an optimized formulation of QTsome lipid nanoparticles (QTPlus) is utilized to deliver an anti-miR-21 (AM21) against cancer. The miR-21 downstream gene regulation and antitumor activity is evaluated using mouse and human cancer cells and macrophages.

Ivermectin Enhanced Antitumor Activity of Resiquimod in a Co-Loaded Squalene Emulsion.

Immunogenic cell death (ICD) plays an important role in sensitizing tumor cells to antigen-presenting cells followed by antitumor immunity. However, a successful antitumor response by ICD requires both apoptotic tumor microenvironments and activated immune systems. Ivermectin (IVM) has been shown to induce cell apoptosis through autophagy which can be a great candidate for ICD therapy.

AZD5153, a Bivalent BRD4 Inhibitor, Suppresses Hepatocarcinogenesis by Altering BRD4 Chromosomal Landscape and Modulating the Transcriptome of HCC Cells.

BRD4, a chromatin modifier frequently upregulated in a variety of neoplasms including hepatocellular cancer (HCC), promotes cancer cell growth by activating oncogenes through its interaction with acetylated histone tails of nucleosomes. Here, we determined the anti-HCC efficacy of AZD5153, a potent bivalent BRD4 inhibitor, and elucidated its underlying molecular mechanism of action. AZD5153 treatment inhibited HCC cell proliferation, clonogenic survival and induced apoptosis in HCC cells.

Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy.

Lipid-based nanoparticles (LBNPs) are biocompatible and biodegradable vesicles that are considered to be one of the most efficient drug delivery platforms. Due to the prominent advantages, such as long circulation time, slow drug release, reduced toxicity, high transfection efficiency, and endosomal escape capacity, such synthetic nanoparticles have been widely used for carrying genetic therapeutics, particularly nucleic acids that can be applied in the treatment for various diseases, including congenital diseases, cancers, virus infections, and chronic inflammations. Despite great merits and multiple successful applications, many extracellular and intracellular barriers remain and greatly impair delivery efficacy and therapeutic outcomes.

CpG Oligodeoxynucleotides for Anticancer Monotherapy from Preclinical Stages to Clinical Trials.

CpG oligodeoxynucleotides (CpG ODNs), the artificial versions of unmethylated CpG motifs that were originally discovered in bacterial DNA, are demonstrated not only as potent immunoadjuvants but also as anticancer agents by triggering toll-like receptor 9 (TLR9) activation in immune cells. TLR9 activation triggered by CpG ODN has been shown to activate plasmacytoid dendritic cells (pDCs) and cytotoxic T lymphocytes (CTLs), enhancing T cell-mediated antitumor immunity. However, the extent of antitumor immunity carried by TLR agonists has not been optimized individually or in combinations with cancer vaccines, resulting in a decreased preference for TLR agonists as adjuvants in clinical trials.

A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod.

Agonists for toll-like receptors (TLRs) have shown promising activities against cancer. In the present study, a squalene-based nanoemulsion (NE) was loaded with resiquimod, a TLR7/8 agonist for therapeutic delivery. R848 NE was developed and characterized for long-term stability.

A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors.

In recent years, human serum albumin (HSA) has been characterized as an ideal drug carrier in the cancer arena. Caveolin-1 (Cav-1) has been established as the principal structural protein of caveolae and, thus, critical for caveolae-mediated endocytosis. Cav-1 has been shown to be overexpressed in cancers of the lung and pancreas, among others.