Abstract
Hybrid inorganic-organic core-shell nanoparticles (CSNPs) are an emerging paradigm of nanodrug carriers in the targeted photodynamic therapy (TPDT) of cancer. Typically, metallic cores and organic polymer shells are used due to their submicron sizes and high surface to volume ratio of the metallic nanoparticles (NPs), combined with enhances solubility, stability, and absorption sites of the organic polymer shell. As such, the high loading capacity of therapeutic agents such as cancer specific ligands and photosensitizer (PS) agents is achieved with desired colloidal stability, drug circulation, and subcellular localization of the PS agents at the cancer site. This review highlights the synthesis methods, characterization techniques, and applications of hybrid inorganic-organic CSNPs as loading platforms of therapeutic agents for use in TPDT. In addition, cell death pathways and the mechanisms of action that hybrid inorganic-organic core-shell nanodrug systems follow in TPDT are also reviewed. Nanodrug systems with cancer specific properties are able to localize within the solid tumor through the enhanced permeability effect (EPR) and bind with affinity to receptors on the cancer cell surfaces, thus improving the efficacy of short-lived cytotoxic singlet oxygen. This ability by nanodrug systems together with their mechanism of action during cell death forms the core basis of this review and will be discussed with an overview of successful strategies that have been reported in the literature.
Highlights
In targeted photodynamic therapy (TPDT), two common approaches are used to improve tumor targeting specificity of PS agents, the first approach being the conjugation of PS agents to cancer specific biomolecules to improve accumulation of PS agents at the tumor tissue through active targeting [17], and the second approach takes advantage of the leaky vasculature system around tumor tissue to deliver PS agents through passive targeting when conjugated to nanocarriers such as core-shell nanoparticles (CSNPs) [17,42]
The absorption sites on the organic polymer shell make it easy to attach PS agents and cancer specific ligands for TPDT through enhanced permeability and retention (EPR) and binding onto receptors overexpressed on the cancer cell surface
Another advantage of hybrid inorganic-organic nanodrug systems is that they are able to be designed with specificity to localize within certain cellular compartments, such as the mitochondria, lysosomes, cytosol, or cytoplasm, which can allow for efficient cell death through the disruption of intracellular organelles
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Of interest to this review are hybrid inorganic-organic core-shell nanoparticles (CSNPs) for application in the targeted photodynamic therapy (TPDT) of cancer. NPs have sub-micron sizes and high surface to volume properties [26] that allow for the loading and delivery of therapeutic agents through passive and active targeting of the solid tumor. Since the modality of PDT is dependent on the subcellular localization of the PS agents to optimize the efficacy of cytotoxic singlet oxygen or ROS through different cell death pathways [24,25], this review highlights the specific target ligands and strategies that have been adopted to deliver and concentrate PS agents in the solid tumor, achieving an efficient PDT effect on cancer cells through the cytotoxic singlet oxygen killing of cancer cells [17]
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