Drug Delivery Strategies for Age-Related Diseases

Abstract

Drug delivery systems (DDSs) enable the controlled release of drugs in the body. DDSs have attracted increasing attention for the treatment of various disorders, including cancer, inflammatory diseases, and age-related diseases. With recent advancements in our understanding of the molecular mechanisms of aging, new target molecules and drug delivery carriers for age-related diseases have been reported. In this review, we will summarize the recent research on DDSs for age-related diseases and identify DDS strategies in the treatment of age-related diseases.

Keywords: SASP; age-related diseases; drug delivery systems; p16INK4A; senescence-associated β-galactosidase.

Figure 1

Mechanism of generation of senescent cells. One of the hallmarks of aging at the cellular level is a prolonged, generally irreversible cell cycle arrest accompanied by damage to secretory functions, macromolecules, and metabolic changes. DNA damage caused by age-related stress or physiological processes activates p53, which in turn activates the CDK2 inhibitor p21^WAF1/CIP1 (CDKN1A). DNA damage also activates the CDK4/6 inhibitor p16^INK4A (CDKN2A). These factors dephosphorylate and persistently activate RB family proteins, resulting in inhibition of E2F transcriptional activation, cell cycle arrest, and accumulation of senescent cells.

Figure 2

Cytoplasmic DNA from DNA damage in senescent cells can be an SASP-inducing signal. A typical signaling mechanism of SASP is the activation of the cGAS/STING pathway [26]. Typical transcriptional regulatory mechanisms of SASP are mainly regulated by two major factors, NF-κB and CCAAT/enhancer binding protein β (C/EBPβ). Inhibition of SASP by NOTCH1 results from repression of C/EBPβ transcription.

Figure 3

Silica-based scaffold (MCM41) capable of encapsulating a wide variety of drugs coated with a hexametric beta-1,4-galactooligosaccharide coating.

Figure 4

The nanosystem, comprising sphingomyelin and coated with 4N1K, is designed to target CD47 receptors. TSP-1/CD47 receptors exert an inhibitory effect on the replication and proliferation of cells.

Figure 5

The drug increases BCLXL expression in CSE (cigarette smoke extract)-induced aged HFL-1 cells, decreases the BCL2/BIX ratio, and selectively eliminates HFL-1 cell activity.

Figure 6

Magnetic nanoparticle SMN + miRNA-122 liver translational repressor + iBax mRNA (BAX; BCLA-2-related protein X) encapsulation + BTSA1 (BAX activator) membrane loading + EV (extracellular vesicle).

Figure 7

In a β-galactosidase-dependent manner, these agents induce apoptosis of senescent cells.

Figure 8

Resveratrol-encapsulated gold nanoparticles (RGNPs) inhibit cellular senescence and suppress SA-β-Gal and SASP, resulting in anti-aging and anti-inflammatory effects and reducing cataract symptoms. Ceria nanoparticles (CeNPs) inhibit osteoarthritis by suppressing not only ROS but also p16, p21, iNOS, COX2, MMP3, ADAMTS5, IL-6, and TNFα.

Figure 9

A schematic representation of the major senescent cell-targeted DDSs that have been published within the last five years.