Light-Harvesting Ionic Dendrimer Porphyrins as New Photosensitizers for Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a promising therapeutic modality for treatment of solid tumors. In this study, third-generation aryl ether dendrimer porphyrins (DPs) with either 32 quaternary ammonium groups (32(+)DPZn) or 32 carboxylic groups (32(-)DPZn) were evaluated as a novel, supramolecular class of photosensitizers for PDT. DPs showed a different cell-association profile depending on the positive or negative charge on the periphery, and both DPs eventually localized in membrane-limited organelles. In contrast, protoporphyrin IX (PIX), which is a hydrophobic and relatively low molecular weight photosensitizer used as a control in this study, diffused through the cytoplasm except the nucleus. Confocal fluorescent imaging using organelle-specific dyes indicated that PIX induced severe photodamage to disrupt membranes and intracellular organelles, including the plasma membrane, mitochondrion, and lysosome. On the other hand, cells treated with DPs kept the characteristic fluorescent pattern of such organelles even after photoirradiation. However, notably 32(+)DPZn achieved remarkably higher (1)O(2)-induced cytotoxicity against LLC cells than PIX. Furthermore, both dendrimer porphyrins had far lower dark toxicity as compared with PIX, demonstrating their highly selective photosensitizing effect in combination with a reduced systemic toxicity.

Principles of Directed Electronic Energy Transfer

“…Energy harvesting dendrimers are increasingly being developed for use as organic light-emitting diode materials [47][48][49][50]. Furthermore, energy pooling porphyrin dendrimers have begun to find an application in photodynamic therapy (PDT) as photosensitisers [51][52][53] -energy harvesting here leading to the targeted photochemical destruction of cancer cells via the generation of singlet oxygen.…”

Dendrimer porphyrin-based self-assembled nano-devices for biomedical applications

“…In addition, large dendritic wedges effectively prevent aggregation. [31][32][33][34] The high solubility of DP and DPc permits their use in PDT, a promising technology for less invasive cancer treatments. PDT involves the systemic administration of photosensitizers (PS) followed by the irradiation of the target tissue with laser light.…”

Polyester Dendrimers

“…Here, both free base and zinc-cored tetraphenylporphyrin (TPPH 2 and TPPZn) were used, from which the dendrons were divergently grown using 38. Porphyrins were selected as core molecules because of their potential applications in many areas [156][157][158][159]. Reports dealing with porphyrins decorated with dendrimers had previously appeared [112,[160][161][162][163][164][165][166][167][168].…”