Doxorubicin-Loaded Photosensitizer-Core pH-Responsive Copolymer Nanocarriers for Combining Photodynamic Therapy and Chemotherapy

Abstract

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.

Recent Progress in Phthalocyanine-Polymeric Nanoparticle Delivery Systems for Cancer Photodynamic Therapy

“…DOX was also used as the chemotherapeutic agent in four-armed star-shaped copolymer based on ZnPc as the PS ( Scheme 12 ). The copolymer presented a tendency to self-assemble into DOX-loaded micelles [ 78 ], which had high tumor targeting and anticancer effects thanks to a combination of the two therapies. 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 successfully designed and prepared.…”

Recent Advances in pH- or/and Photo-Responsive Nanovehicles

“… Molecular structure of PDCZP and illustration of its pH-dependent drug release and combination of chemotherapy and photodynamic therapy. Reproduced from [ 169 ] with permission, copyright 2017, American Chemical Society. …”

“…The DOX-loaded nanovehicles showed the formation of 50 nm-sized spherical particles at pH 7.4. In the nanovehicles delivered to tumor cells, the rapid DOX release was triggered by the acidic pH, resulting in enhanced antitumor effects through chemotherapy with DOX and PDT with core PS under light irradiation (Figure 10) [169]. [169] with permission, copyright 2017, American Chemical Society.…”

“…These results showed that the DOX-loaded dendrimers exhibited drug release when triggered by UV irradiation or under acidic conditions and that, consequently, the controlled release system based on SP was developed by either adjusting UV/Vis light illumination or changing the pH values [158]. In addition, Wang and co-workers designed and prepared chi- [169] with permission, copyright 2017, American Chemical Society.…”

Photo-Based Nanomedicines Using Polymeric Systems in the Field of Cancer Imaging and Therapy

“…For dual delivery systems, Zhang et al [ 166 ] reported the high tumor-targeting and anticancer effects of Dox-loaded photosensitizer-core pH-responsive copolymer nanocarrier prepared from a 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). The nanocarriers loaded with zinc phthalocyanine (ZnPc) had a long emission wavelength (max.…”