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.