Here, we report the rational design of a new third-generation photosensitizer (PS), a chlorin conjugated with galactodendritic units, ChlGal, to improve the effectiveness of bladder cancer treatment. ChlGal shows better photochemical and photophysical properties than a recently reported homologous porphyrin, PorGal. In addition to inheriting excellent photostability, the ability to generate singlet oxygen, and the ability to interact with the proteins galectin-1 and human serum albumin (HSA), ChlGal exhibits high absorption in the red region of the electromagnetic spectrum. In vitro studies of anticancer activity of ChlGal revealed that once this PS is taken up by UM-UC-3 bladder cancer cells, it induces high cytotoxicity after a single dose of light irradiation. In HT-1376 bladder cancer cells resistant to therapy, a second light irradiation treatment enhanced in vitro and in vivo photodynamic efficacy. The enhanced phototoxicity in HT-1376 cancer cells seems to be due to the ability of ChlGal to accumulate in the mitochondria, via facilitative glucose transporter 1 (GLUT1), in the period between single and repeated irradiation. A photodynamic therapy (PDT) regimen using an extra dose of light irradiation and ChlGal as PS represents a promising strategy in treating resistant cancers in a clinical setting.

KPF report that they are employees of PerkinElmer, a manufacturer of optical and PET imaging equipment. LSM reports that he has received grant support from MedImmune, Pfizer, Moderna Therapeutics, Regeneron Pharmaceuticals, and Boehringer Ingelheim and consulting fees from Integrated BioTherapeutics, related to Staphylococcus aureus vaccines and therapeutics. JMVD reports that he has filed a patent application (WO2015/088346) on the use of 1D9, which is owned by his employer University Medical Center Groningen. NMB reports that he has received consulting fees from Zimmer Biomet, Bonesupport, Daiichi Sankyo, and Onkos and that he is a board or committee member of the Musculoskeletal Tumor Society and Orthopaedic Research and Education Foundation.

Conflict of interest: KPF reports that he is an employee of PerkinElmer Inc., the manufacturer of optical and PET imaging equipment. GMVD is CEO, founder, and shareholder of AxelaRx/ TRACER group and CSO AxelaRx Biosciences Inc. JMVD has filed a patent application on the use of 1D9 (US 9,944,694 B2), which is owned by his employer University Medical Center Groningen.

Antimicrobial resistance is among the biggest threats to mankind today. There are two alternative antimicrobial therapies that may help to control multidrug-resistant bacteria.