A novel drug delivery system that combines mesoporous silica nanoparticles (MSNs) with oxaliplatin and the HCE6 photosensitizer (OH‑MSNs) provides additional evidence for the combination of chemotherapy with photodynamic therapy (PDT) as therapeutic intervention in cholangiocarcinoma (CCA). The study’s authors explained that “basing on the enhanced permeability and retention theory that the circulating nanoparticles are easily accumulated in tumor areas, the OH‑MSNs are capable of exhibiting higher cytotoxicity compared to single HEC6 or oxaliplatin.”
OH‑MSNs inhibited tumor growth in tumor‑bearing nude mice (n=4). Tumor response was assessed after intravenous administration of MSNs (0.1 mmol) loaded with oxaliplatin (0.5 mmol) and HCE6 (0.5 mmol), and 20‑minutes illumination (120 J cm−2, 0.2 W, light source placed 2 cm away from the tumor) at 24 hours after dosing. Results showed that OH‑MSNs treatment was more effective in both reducing tumor size and promoting apoptosis when compared with oxaliplatin-MSNs or either oxaliplatin or HCE6 as standalone treatments.
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OH‑MSNs also decreased cell viability and proliferation, and promoted apoptosis in FRH0201 and HuCCT1 human cholangiocarcinoma cells.
Regarding the underlying molecular mechanisms, the researchers found that OH‑MSNs upregulated the expression of pro-apoptotic and autophagy‑promoting factors, while downregulated the expression of anti-apoptotic and autophagy-inhibiting factors more efficiently than oxaliplatin‑MSNs.
Drug release from OH-MSNs was higher in acidic conditions, such as those found in tumor microenvironment.
HCE6 did not exhibit any therapeutic effect when used as standalone treatment and did not provide added‑value to oxaliplatin treatment, unless both substances were combined in MSNs.
MSNs have been explored as a convenient drug delivery system over the past decades due to their ability to transport molecular cargo into living cells and control drug release. These characteristics allow for an efficient therapeutic effect, while ensuring diminished toxicity and adverse effects. Additionally, MSNs can support the formation of photosensitizers‑induced free radicals.
Zhang P-J, Liu M-D, Fan F-Y, Liu K-X. A study on mesoporous silica loaded with novel photosensitizers HCE6 and oxaliplatin for the treatment of cholangiocarcinoma. Front Oncol. 2021;11. doi:10.3389/fonc.2021.665182