Nanotechnology-based photothermal therapy has emerged as a promising treatment for cancer during the past decade. However, heterogeneous laser heating and limited light penetration can lead to incomplete tumor cell eradication. Here, we developed a method to overcome these limitations by combining chemotherapy with photothermal therapy using paclitaxel-loaded gold nanorods. Paclitaxel was loaded to gold nanorods with high density (2.0 × 10(4) paclitaxel per gold nanorod) via nonspecific adsorption, followed by stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. Paclitaxel was entrapped in the hydrophobic pocket of the polymeric monolayer on the surface of gold nanorods, which allows direct cellular delivery of the hydrophobic drugs via the lipophilic plasma membrane. Highly efficient drug release was demonstrated in a cell membrane mimicking two-phase solution. Combined photothermal therapy and chemotherapy with the paclitaxel-loaded gold nanorods was shown to be highly effective in killing head and neck cancer cells and lung cancer cells, superior to photothermal therapy or chemotherapy alone due to a synergistic effect. The paclitaxel-gold nanorod enabled photothermal chemotherapy has the potential of preventing tumor reoccurrence and metastasis and may have an important impact on the treatment of head and neck cancer and other malignancies in the clinic.

The preparation and characterization of nanoscale silver sulfide and silver particles in Nafion and perfluorinated sulfonimide ionomer membranes are reported. The results show that the nanoparticles are hosted in the membrane structure in an isolated fashion, with no indication of channels-like domains as proposed in the ion cluster model for the ionomer membranes. These randomly dispersed nanoparticles are also significantly larger than the average size of the reverse micelle-like hydrophilic cavities estimated in the literature for Nafion membrane. The properties of the silver sulfide and silver nanoparticles are presented, and their implications to the understanding of membrane nanoscopic structural details are discussed.

Despite the advancement of photodynamic therapy and photothermal therapy, the ability to form compact nanocomplex for combined photodynamic and photothermal cancer therapy under a single near infrared irradiation remains limited. In this work, we prepared an integrated sub-100 nm nanosystem for simultaneous near infrared photodynamic and photothermal cancer therapy. The nanosystem was formed by adsorption of silicon 2,3-naphthalocyanine dihydroxide onto gold nanorod followed by covalent stabilization with alkylthiol linked polyethylene glycol. The effects of alkylthiol chain length on drug loading, release and cell killing efficacy were examined using 6-mercaptohexanoic acid, 11-mercaptoundecanoic acid and 16-mercaptohexadecanoic acid. We found that the loading efficiency of silicon 2,3-naphthalocyanine dihydroxide increased and the release rate decreased with the increase of the alkylthiol chain length. We demonstrated that the combined near infrared photodynamic and photothermal therapy using the silicon 2,3-naphthalocyanine dihydroxide-loaded gold nanorods exhibit superior efficacy in cancer cell destruction as compared to photodynamic therapy and photothermal therapy alone. The nanocomplex stabilized with 16-mercaptohexadecanoic acid linked polyethylene glycol provided highest cell killing efficiency as compared to those stabilized with the other two stabilizers under low drug dose. This new nanosystem has potential to completely eradicate tumors via noninvasive phototherapy, preventing tumor reoccurrence and metastasis.

The chelation following photodissociation of CO for cyclopentadienyl manganese tricarbonyl derivatives with a bifunctional side chain has been investigated. Previous studies show that steady-state irradiation of 1 (Mn{η5-C5H4CH2COR}(CO)3, R = 2-pyridyl) leads to CO dissociation and formation of O-chelate 2 with smaller amounts of N-chelate 3. Subsequently, 2 rearranges thermally to 3. A new preparation for 1 is reported, while analogues 4 (R = phenyl) and 5 (R = 4-pyridyl) are prepared for the first time. Steady-state UV–vis, FTIR, and NMR studies of 4 and 5 in heptane demonstrate that O-chelates 6 and 7, respectively, are formed with the side-chain oxygen but decay on the minute time scale. The linkage isomerization of O-chelate 2 to 3 is faster than the decay observed for the O-chelate 6 (R = 2-pyridyl versus Ph), even in the presence of 0.1 M pyridine for the latter. Following irradiation of 4 during time-resolved infrared studies in heptane, ultrafast O-chelation is observed but not ultrafast solvent coordination. Ultrafast O-chelation is also observed for 5 along with an unidentified transient. Following irradiation of 1, ultrafast O- and N-chelation are observed, to the exclusion of ultrafast solvent coordination. This result suggests that chelate formation is a subpicosecond process and that both chelates are formed independently. A split in the otherwise degenerate stretching bands for 4 and 5 in FTIR spectra suggests that there is significant electronic communication between the side chain and the metal carbonyl groups. The results suggest that ultrafast chelation is favored by side-chain conformations that position a functional group near the metal center.

Chromium arene tricarbonyl complexes with tethered pyridinyl groups [Cr{η 6 -C 6 H 5 (CH 2 ) n (2-Py)}(CO) 3 ] (4−6) (2-Py = 2-pyridinyl, n = 1−3, respectively) were synthesized and irradiated to form the chelates [Cr{η 6 -C 6 H 5 (CH 2 ) n (2-Py)-κN}(CO) 2 ] (7−9). Studies examined the effect of ring size and structure on chromophore λ max , stability, and photosensitivity, which are factors important for photochromes based on linkage isomerization of tethered functional groups. The studies also include [Cr{η 6 -C 6 H 5 CH(2-Py)CH 2 CHCH 2 }(CO) 3 ] (3), which has a bifunctional tether of propenyl and pyridinyl groups, and irradiation produces the linkage isomers [Cr{η 6 -C 6 H 5 (CH(2-Py)CH 2 CHCH 2 )-κN}(CO) 2 ] (1) and [Cr{η 6 -C 6 H 5 (CH(2-Py)CH 2 CHCH 2 )(η 2 -CHCH 2 )}(CO) 2 ] (2). X-ray crystal structures for 7−9 show that the dihedral angle between the coordinated pyridinyl groups and the phenyl-chromium centroid increases from 1 to 73°(n = 1−3, respectively). The experimental and TDDFT computed optical changes accompanying an increase in the dihedral angle are modest and not monotonic for 7−9 due to structural changes inherent in the chelate rings. An increase in Cr−N bond lengths and decrease in their bond energies were observed experimentally and computationally for the series of 7−9. The quantum yields for formation of the five-, six-, and seven-membered chelate rings during the conversion of 4−6 to 7−9, respectively, were within experimental error for that observed for conversion of 10 [Cr{η 6 -C 6 H 6 }(CO) 3 ] with free pyridine to 11 [Cr{η 6 -C 6 H 6 }(C 5 H 5 N-κN)(CO) 2 ], indicating that the product-determining step precedes chelation. The enthalpies for chelation of 4−6 to 7−9 were determined independently by photoacoustic calorimetry and DFT computations. The computationally derived mechanism for thermal isomerization of 1 to 2 indicates that the transition state is a dissociative interchange with a free energy of activation of 27.9 kcal mol −1 (1 → 2), a result consistent with an experimentally bistable photochrome. The results indicate which tether properties are important for optimizing photochrome performance. ■ INTRODUCTIONRecent studies have examined organometallics that undergo a linkage isomerization as a photochromic mechanism. 1,2 This is a departure from other studies where the metal serves as a spectator and binds to a photochromic ligand but is not involved in bond-forming or -breaking processes. 3 Our group investigates the design of photochromes based on linkage isomerization: in particular, systems where functional groups tethered to a metal center undergo a photoinitiated exchange (Scheme 1). The isomerization in this case relies on the reversible interconversion of two chelates, each with a different coordinated functional group and ultimately a different ring system. The length of a tether and its composition (heteroatom, branching, or multiple bonds) are anticipated to affect the chelate ring properties, including the rate of chelate ring formation, ring strain, and ...