Keratin nanoparticles co-delivering Docetaxel and Chlorin e6 promote synergic interaction between chemo- and photo-dynamic therapies

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2019-10, Vol.199, p.111598-111598, Article 111598
• Main Authors: Gaio, Elisa, Guerrini, Andrea, Ballestri, Marco, Varchi, Greta, Ferroni, Claudia, Martella, Elisa, Columbaro, Marta, Moret, Francesca, Reddi, Elena
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biocompatibility; Biocompatible Materials - chemistry; Cell Membrane Permeability; Cell Survival - drug effects; Chemotherapy; Chlorin e6; Combination therapy; Cytotoxicity; Docetaxel; Docetaxel - pharmacology; Drug Carriers - chemistry; Drug Compounding - methods; Drug Liberation; Drug Synergism; HeLa Cells; Humans; Keratin; Keratin nanoparticle; Keratins - chemistry; Monolayers; Nanoparticles; Nanoparticles - chemistry; Neoplasms - drug therapy; Neoplasms - radiotherapy; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - chemistry; Porphyrins - pharmacology; Spheroids; Spheroids, Cellular - drug effects; Synergism; Toxicity; Tumor spheroid
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2019.111598

The combination of chemotherapy and photodynamic therapy (PDT) is considered a valuable strategy for increasing therapeutic response in cancer treatment, and the re-formulation of pharmaceuticals in biocompatible nanoparticles (NPs) is particularly appealing for the possibility of co-loading drugs exerting cytotoxicity by different mechanisms, with the aim to produce synergic effects. We report the in-water synthesis of a novel keratin-based nanoformulation for the co-delivery of the antimitotic Docetaxel (DTX) and the photosensitizer Chlorin e6 (Ce6). The drug-induced aggregation method allowed the formation of monodisperse NPs (DTX/Ce6-KNPs) with an average diameter of 133 nm and loaded with a drug ratio of 1:1.8 of Ce6 vs DTX. The efficacy of DTX/Ce6-KNPs was investigated in vitro in monolayers and spheroids of DTX-sensitive HeLa (HeLa-P) and DTX-resistant HeLa (HeLa-R) cells. In monolayers, the cytotoxic effects of DTX/Ce6-KNPs toward HeLa-P cells were comparable to those induced by free DTX + Ce6, while in HeLa-R cells the drug co-loading in KNPs produced synergic interaction between chemotherapy and PDT. Moreover, as respect to monotherapies, DTX/Ce6-KNPs induced stronger cytotoxicity to both HeLa-P and HeLa-R multicellular spheroids and reduced their volumes up to 50%. Overall, the results suggest that KNPs are very promising systems for the co-delivery of chemotherapeutics and PSs, favoring synergic interactions between PDT and chemotherapy. [Display omitted] •Docetaxel and Chlorin e6 were efficiently co-loaded on keratin nanoparticles (DTX/Ce6-KNPs) through aggregation method.•Ce6 in DTX/Ce6-KNPs retained its ability to produce reactive oxygen species and singlet oxygen upon light irradiation.•DTX/Ce6-KNPs synergistically killed DTX-sensitive and DTX-resistant HeLa cells in monolayers and tridimensional spheroids.