Abstract
Cancer is a major public health problem and one of the leading causes of death. However, traditional cancer therapy may damage normal cells and cause side effects. Many targeted drug delivery platforms have been developed to overcome the limitations of the free form of therapeutics and biological barriers. The commonly used cancer cell surface targets are CD44, matrix metalloproteinase-2, folate receptors, etc. Once the drug enters the cell, active delivery of the drug molecule to its final destination is still preferred. The subcellular targeting strategies include using glucocorticoid receptors for nuclear targeting, negative mitochondrial membrane potential and N-acetylgalactosaminyltransferase for Golgi apparatus targeting, etc. Therefore, the most effective way to deliver therapeutic agents is through a sequential drug delivery system that simultaneously achieves cellular- and subcellular-level targeting. The dual-targeting delivery holds great promise for improving therapeutic effects and overcoming drug resistance. This review classifies sequential drug delivery systems based on final targeted organelles. We summarize different targeting strategies and mechanisms and gave examples of each case.
Highlights
Cancer is a devastating health issue leading to high mortality rates worldwide with a complex pathophysiology
The carriers conjugated with mitochondrial localizing sequence (MLS) peptides and folic acid (FA) could target the folate receptors on the surface of most cancer cells
Proteins and peptides are biocompatible with cells. They can serve as drug delivery carriers to achieve specific targeting at the cellular level [51]
Summary
Cancer is a devastating health issue leading to high mortality rates worldwide with a complex pathophysiology. Passive targeting relies on the accumulation of the nanoparticles with specific physicochemical properties (size, charge, etc.) in the tumor tissue. This accumulation is due to the enhanced permeability and retention (EPR) effect and the particular tumor microenvironment [9]. Pharmaceutics 2022, 14, 573 efficiency of the drug delivered to the desired tissues/cells via specific interactions between a targeting moiety on the nanoparticles and cellular/subcellular markers [12]. The active targeted delivery systems in cancer therapy have been extensively reviewed elsewhere [17–20], few of them focused on sequential drug delivery that can target both cellular and subcellular simultaneously. This review highlights the application of cell organelle sequential targeted drug delivery systems in cancer treatments depending on the different types of cellular and subcellular targeting moieties. DOX + retinoic acid chondroitin sulfate chondroitin sulfate peptide peptide polymer silica silica lipid graphene oxide gelatin polysaccharide nanodiamonds polymer silica lipid metal polymer lipid/polymer hybrid nanovehicles (lpnvs) polymer lipid
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