Photodynamic therapy (PDT) is an emerging method for the treatment of cancer. Combination of PDT and chemotherapy is a hot topic though the two therapies could not simultaneously exert their perfect effect in vivo. Here we report a doxorubicin-loaded photosensitizer-core pH-responsive copolymer nanocarrier with high tumor targeting and anticancer effects due to integration of PDT with chemotherapy. The pH-responsive photosensitizer-core four-armed star-shaped copolymer, [methoxy-poly(ethylene glycol)poly(2-(N,N-diethylamino)ethyl methacrylate)-poly(ε-caprolactone)] 4 -zinc β-tetra-(4-carboxyl benzyloxyl)phthalocyanine (PDCZP), was prepared, which was a molecular spherical nanocarrier in aqueous media. The carriers changed from small at high pH to large at low pH (51, 105, and 342 nm at pH 7.4, 6.5, and 5.0, respectively) and the zeta potential gradually increased (7.15, 16.2, and 26.1 mV at the above pH, respectively). PDCZP had a longer emission wavelength (max. 677 nm) than the parent photosensitizer, favoring light penetration through biological tissues. The singlet oxygen ( 1 O 2 ) quantum yield of PDCZP was 0.41. Doxorubicin (DOX) showed rapid release from PDCZP in the acidic media. More importantly, the drug-loaded nanocarriers showed the better in vitro and in vivo anticancer effects under lighting on MCF-7, SW480 cells and HepG2 cells and the murine hepatocellular carcinoma H 22 models than the other groups. PDCZP showed a high tumor targeting effect based on the enhanced permeation and retention effect and its small size. The photosensitizer-core nanocarrier is a promising photodynamic nanocarrier for integrating other therapies.

Photodynamic therapy (PDT) has emerged as an attractive therapeutic treatment for colorectal cancer because of its accessibility through endoscopy and its ability to selectively target tumors without destroying the anatomical integrity of the colon. We therefore investigated the therapeutic relevance of the interplay between autophagy and apoptosis in Photosan-II (PS-II)-mediated photodynamic therapy (PS-PDT) in in vitro and in vivo models for human colorectal cancer. We observed that PS-PDT-induced dose-dependently triggered apoptosis and autophagy in both SW620 and HCT116 cells. PS-PDT-treated SW620 cells exhibited nuclear condensation and increased levels of cleaved caspase-3, PARP and Bax, which is reminiscent of apoptosis. PS-PDT also induced autophagic vacuoles, double membrane autophagosome structures and the autophagy-related proteins P62, Bcl-2, ATG7 and LC3-II. In addition, the AKT-mTOR pathway was downregulated, while AMPK was upregulated in PS-PDT-treated cells. Inhibiting autophagy using chloroquine or by downregulating ATG7 using shRNA further upregulated apoptosis, suggesting autophagy was probably was protective to PS-PDT-treated tumor cells. In vivo relevance was demonstrated when a combination of chloroquine and PS-PDT significantly reduced the tumor size in a xenograft mice model. Our findings demonstrate that combination therapy using PS-PDT and autophagy inhibitors may be an effective approach to treating colorectal cancer patients.

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We demonstrate a diode end-pumped Yb, Er, Ho:Gd(1.17)Y(1.83)Sc(2)Ga(3)O(12) (GYSGG) laser operated at 2.79 μm in continuous-wave mode. Spectral analysis shows that Yb(3+) and Ho(3+) act as sensitizer and deactivator ions, respectively. Pumping with a 967 nm laser diode produces the maximum output power of 411 mW, corresponding to optical-optical conversion and slope efficiencies of 11.6% and 13.1%, respectively. The minimum laser threshold is only 81 mW because of Ho(3+) doping. The laser properties are only slightly influenced by 100 mrad gamma irradiation. The Yb, Er, Ho:GYSGG crystal possesses excellent radiation resistance and is a potential laser gain medium in radiant environments.

A thermal-bonded Nd:YAG planar waveguide laser with an O-O conversion efficiency of 58% was demonstrated for the first time to our knowledge. The waveguide was end-pumped by a fiber-coupled laser diode operating at 808 nm. A maximum output power of 2.90 W at 1064 nm was achieved with an M 2 value of 2.6 in the guided direction for a pump power of 5.0 W. The results indicate that the planar waveguide laser can reach high O-O conversion efficiency and has a promising prospect for efficient and high optical quality laser sources. LD