Porphyrin–Gold Nanomaterial for Efficient Drug Delivery to Cancerous Cells

Abstract

With an aim to overcome multidrug resistance (MDR), nontargeted delivery, and drug toxicity, we developed a new nanochemotherapeutic system with tetrasodium salt of meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) armored on gold nanoparticles (TPPS-AuNPs). The nanocarrier is able to be selectively internalized within tumor cells than in normal cells followed by endocytosis and therefore delivers the antitumor drug doxorubicin (DOX) particularly to the nucleus of diseased cells. The embedment of TPPS on the gold nanosurface provides excellent stability and biocompatibility to the nanoparticles. Porphyrin interacts with the gold nanosurface through the coordination interaction between gold and pyrrolic nitrogen atoms of the porphyrin and forms a strong association complex. DOX-loaded nanocomposite (DOX@TPPS-AuNPs) demonstrated enhanced cellular uptake with significantly reduced drug efflux in MDR brain cancer cells, thereby increasing the retention time of the drug within tumor cells. It exhibited about 9 times greater potency for cellular apoptosis via triggered release commenced by acidic pH. DOX has been successfully loaded on the porphyrin-modified gold nanosurface noncovalently with high encapsulation efficacy (∼90%) and tightly associated under normal physiological conditions but capable of releasing ∼81% of drug in a low-pH environment. Subsequently, DOX-loaded TPPS-AuNPs exhibited higher inhibition of cellular metastasis, invasion, and angiogenesis, suggesting that TPPS-modified AuNPs could improve the therapeutic efficacy of the drug molecule. Unlike free DOX, drug-loaded TPPS-AuNPs did not show toxicity toward normal cells. Therefore, higher drug encapsulation efficacy with selective targeting potential and acidic-pH-mediated intracellular release of DOX at the nucleus make TPPS-AuNPs a “magic bullet” for implication in nanomedicine.

Singlet oxygen generation by porphyrins and metalloporphyrins revisited: A quantitative structure-property relationship (QSPR) study

“…Porphyrins represent a unique class of organic photosensitizers due to a combination of easily controllable photophysical properties and synthetic accessibility [3]. Porphyrins have multiple applications including drug delivery [4,5], bioimaging [6,7], and non-linear optics [8,9] to name a few. One of the most intriguing properties of porphyrins is their ability to produce singlet oxygen with high quantum yield under visible light irradiation, which is used for the treatment of skin diseases such as psoriasis [10], port-wine stains [11], as well as different types of cancer like mycosis fungoides (a type of a cutaneous T-cell lymphoma) [12], malignant mesothelioma [13], glioma [14], brain tumor [15], fibrosarcoma [16], colorectal cancer [17], osteosarcoma [18].…”

Integrating Stimuli-Responsive Properties in Host-Guest Supramolecular Drug Delivery Systems

“…5A ). In an acidic environment, the hydrogen bonding of the porphyrin to both the gold surface and drug are weakened, dissociating the ternary complex and releasing active drug 102.…”

“…The complex dissociates under acidic conditions as a result of competitive interactions with H + ions. Figure adapted and used according to terms of use of 102. Copyright 2018 American Chemical Society.…”

Encapsulation of Gold Nanorods with Porphyrins for the Potential Treatment of Cancer and Bacterial Diseases: A Critical Review

“…The goal is to increase and improve on the multidrug resistance, nanotargeted delivery, and the toxicity of the drugs. Multifunctional nanocomposites of meso-tetrakis-(4-sulfonatophenyl) porphyrin (TPPS), gold nanorods, and DOX (DOX@TPPS-AuNRs) were synthesized by Bera and his colleagues [230]. The resulting composite material showed improved cellular uptake by the cells and showed no cell toxicity.…”

“…Photodynamic therapy (PDT) is the use of a photosensitive agent on tissues to treat cancer or bacterial infections followed by photoirradiation. This is a clinical treatment used in different diseases [12, 232–234]. It takes place by the administration of a photosensitizer in the body of a patient to accumulate on the tumor.…”