Enhanced Antitumor Activity of the Photosensitizer meso-Tetra(N-methyl-4-pyridyl) Porphine Tetra Tosylate through Encapsulation in Antibody-Targeted Chitosan/Alginate Nanoparticles

Abstract

meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species in targeted tumor cells. However, TMP is highly hydrophilic, and therefore, its ability to accumulate intracellularly is limited. In this study, a strategy to improve TMP uptake into cells has been investigated by encapsulating the compound in a hydrogel-based chitosan/alginate nanoparticle formulation. Nanoparticles of 560 nm in diameter entrapping 9.1 μg of TMP per mg of formulation were produced and examined in cell-based assays. These particles were endocytosed into human colorectal carcinoma HCT116 cells and elicited a more potent photocytotoxic effect than free drug. Antibodies targeting death receptor 5 (DR5), a cell surface apoptosis-inducing receptor up-regulated in various types of cancer and found on HCT116 cells, were then conjugated onto the particles. The conjugated antibodies further enhanced uptake and cytotoxic potency of the nanoparticle. Taken together, these results show that antibody-conjugated chitosan/alginate nanoparticles significantly enhanced the therapeutic effectiveness of entrapped TMP. This novel approach provides a strategy for providing targeted site-specific delivery of TMP and other photosensitizer drugs to treat colorectal tumors using PDT.

Influence of N atom number and form on the photodynamic activities of zinc phthalocyanines

“…Statistical analysis was performed by the Student's t-test [34]. The experiments data in this article were presented as mean result ± standard deviation (SD).…”

Hydrogel-based phototherapy for fighting cancer and bacterial infection

“…However, owning to their high hydrophilicity, their ability to accumulate intracellularly is limited. Abdelghany et al [27] developed a strategy to improve the cellular uptake of TPPS by encapsulating the compound in a chitosan/alginate-based nanogel. The nanoparticles have an average diameter of 560 nm and can be endocytosed by human colorectal carcinoma HCT116 cells much more effectively than free TPPS.…”

Applications of phototheranostic nanoagents in photodynamic therapy

“…For example, the positively charged molecules on the surface of a particular nanotheranostic may interact with the negatively charged molecules on the surface of the cell to internalize the nanoagent. Alternatively, cell penetrating peptides or antibodies attached to the nanoagent may be used for targeting the cell and facilitating internalization [191,192]. Phagocytosis is another possible mechanism of nanoparticle internalization.…”

“…Photosensitizers capable of being activated rapidly by tissue-penetrating light of longer wavelength are desired [208]. Photosensitizers encapsulated in liposomes [170,172,173,190,209] and other particles [177,179,185,190,192] have been extensively discussed. Peptide-conjugated photosensitizers have been reviewed [191].…”

“…Photosensitizers are generally hydrophobic molecules that dissolve poorly in water and therefore are difficult to use in a biological system [192,200]. First generation hydrophobic photosensitizers [200] lacked water solubility and hence their in vitro and in vivo administration was challenging.…”