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.

A gold nanoparticle exhibits strong absorption and emission due to its unique physical geometry and surface plasmon resonance phenomena. A further modification with organic molecules makes it more appropriate for biological applications. The current manuscript illustrated the optical behavior and stability of bilirubin (BR) coated gold (AuBR) nanoparticles, using BR itself as a reducing agent. In addition, FT-IR and steady state fluorescence measurements were performed to illustrate the binding interaction of BR with the Au(III) ion and the nanoparticles. BR showed a strong affinity towards Au(III) and the measured binding constant was ∼4.3 × 10(5) M(-1). It caused reduction of the Au(III) ion and rendered the formation of cubic face centered AuBR nanoparticles, which were ∼20 nm in diameter. The particles were stabilized as BR was bound to the gold nanoparticle surface, which was confirmed by FT-IR measurement. An intense carboxyl C=O stretching vibration at 1695 cm(-1) was observed for the BR powder but was absent for the AuBR nanoparticles. However, two weak bands at ∼1563 and 1391 cm(-1), presumably due to the asymmetric and symmetric stretching vibrations of the carboxylate form (COO(-)), were found for the AuBR nanoparticles. A stretching vibration of lactam C[double bond, length as m-dash]O appeared at 1645 cm(-1) for BR and the band was shifted to 1647 cm(-1) for the AuBR nanoparticles. The stretching modes of pyrrole N-H and lactam N-H were detected at 3406 cm(-1) and 3267 cm(-1), respectively, for BR. However, the pyrrole N-H band shifted to 3446 cm(-1) and became broader for the AuBR nanoparticles. The observed blue shift in the lactam C[double bond, length as m-dash]O and N-H vibrations of the AuBR nanoparticles indicated a weakening/absence of internal hydrogen bonds between the carboxyl groups and the four N-H bonds in the BR moiety. The binding of BR to the surface provides great stability to the nanoparticles, which remained monodispersed in the large pH range (pH 4 to 12) for more than a month. However, under acidic pH conditions the particles associated to form bigger particles and the plasmon resonance band shifted as they grew; the plasmon resonance band shifted from 525 nm (at pH 7.0) to 555 nm (at pH 3.0). The particles also remained stable in the presence of a higher concentration of salt (KCl and NaCl) in the dispersing media.

An analog of coomassie brilliant blue-R (CBB-R) was recently found to act as an antagonist to ATP-sensitive purinergic receptors (P2X7R) and has potential to be used in medicine. With the aim of understanding its transportation and distribution through blood, in this investigation, we measured the binding parameters of CBB-R with bovine hemoglobin (BHG). The molecule specifically bound to a single binding site of the protein with a stoichiometric ratio of 1 : 1 and the observed binding constant Ka was 3.5, 2.5, 2.0 and 1.5 × 10(5) M(-1) at 20 °C, 27 °C, 37 °C and 45 °C, respectively. The measured respective ΔG(0) values of the binding at four temperatures were -30.45, -22.44, -18.04 and -11.95 kJ mol(-1). The ΔH(0) (change in enthalpy) and ΔS(0) (change in entropy) values were -23.6 kJ mol(-1) and -70.66 J mol(-1) respectively in the binding process. The negative value of ΔH(0) and ΔS(0) indicated that the binding of the molecule was thermodynamically favorable. The best energy structure in the molecular docking analysis revealed that CBB-R preferred to be intercalated in the cavity among the α2, β1 and β2 subunits and the binding location was 7.4 Å away from Trp37 in the β2 subunit. The binding of the molecule with the protein was stabilized by hydrogen bonds involving the side chain of two amino acid residues. The residues were Lys104 and Glu101 in the β2 subunit. The binding was further stabilized via hydrogen bond formation between the amide group of the peptide backbone (residue Tyr145 of the β1 subunit) and CBB-R. A shift of the amide I (-C=O stretching) band frequency of ∼8 cm(-1) to low energy was ascribed to the hydrogen bond interaction involving the polypeptide carbonyl of the protein and the CBB-R molecule. In addition, two π-cation interactions between Lys99 of the α2 subunit and Lys104 of the β2 subunit and CBB-R contributed favorably in the binding processes. No substantial change in the soret and Q absorption bands of BHG could be observed in the presence of CBB-R. It indicated that the oxygen binding domain or the heme proximity was not blocked or substantially perturbed due to the binding of CBB-R. The circular dichroism and the molecular dynamics analysis further established that the binding interaction caused no significant alteration in the protein long range secondary structure.

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Silver nanoparticle shows distinctive electrochemical properties, and it has a wide range of applications in most areas of science and technology. In the current work we reported the synthesis of biliverdin protected silver nanosurface (Ag-BV) that could sense Fe­(III) ion via reduction despite of their unfavorable reduction potential in aqueous medium. The addition of Fe­(III) to the Ag-BV suspension resulted an initial red shift in its surface plasmon resonance (SPR) band (420–450 nm) and a color change from straw yellow to deep brown due to the agglomeration of the nanoparticles. Subsequently a redox reaction caused the disappearance of the deep brown color and a significant blue shift occurred in its SPR band (up to 410 nm). The analysis further suggested that the aromatic π system of biliverdin (BV) on the Ag-BV nanosurface could make an electron carrier bridge that favors the transfer of an electron from atomic silver to an empty d orbital of Fe­(III) ion. The reduction of Fe­(III) ion resulted in oxidation of silver nanoparticles and loss of the nanostructure, which were evidenced in transmission electron microscopy analysis. Further investigation revealed that the partial charge on the iron center was ∼+1.16 in the Fe­(II)–biliverdin complex compared to ∼+1.26 in the Fe­(III)–biliverdin complex, suggesting a shift of electron density to the metal ion center. Thus, the biliverdin coated silver nanoparticle could be useful as a specific metal ion detector and a redox modulator for an Fe­(III)/Fe­(II) aqueous system. This might be the first report of its kind as the sensing mechanism involves an exceptional redox type phenomenon instead of mere coagulation of the nanoparticles in the presence of specific ions and produces a different color as an indicator for the ion detection.