Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect.
Ana Lazaro-CarrilloBeatriz Rodríguez-AmigoMargarita MoraMaria Lluïsa SagristáMagdalena CañeteSanti NonellAngeles VillanuevaPublished in: International journal of molecular sciences (2022)
The enhancement of photodynamic therapy (PDT) effectiveness by combining it with other treatment modalities and improved drug delivery has become an interesting field in cancer research. We have prepared and characterized nanoliposomes containing the chemotherapeutic drug irinotecan (CPT11 lip ), the photodynamic agent protoporphyrin IX (PpIX lip ), or their combination (CPT11-PpIX lip ). The effects of individual and bimodal (chemo-phototherapeutic) treatments on HeLa cells have been studied by a combination of biological and photophysical studies. Bimodal treatments show synergistic cytotoxic effects on HeLa cells at relatively low doses of PpIX/PDT and CPT11. Mechanistic cell inactivation studies revealed mitotic catastrophe, apoptosis, and senescence contributions. The enhanced anticancer activity is due to a sustained generation of reactive oxygen species, which increases the number of double-strand DNA breaks. Bimodal chemo-phototherapeutic liposomes may have a very promising future in oncological therapy, potentially allowing a reduction in the CPT11 concentration required to achieve a therapeutic effect and overcoming resistance to individual cancer treatments.
Keyphrases
- photodynamic therapy
- cell cycle arrest
- cancer therapy
- drug delivery
- cell death
- induced apoptosis
- pi k akt
- fluorescence imaging
- papillary thyroid
- reactive oxygen species
- endoplasmic reticulum stress
- single cell
- oxidative stress
- combination therapy
- squamous cell carcinoma
- signaling pathway
- cell therapy
- endothelial cells
- stem cells
- rectal cancer
- locally advanced
- cell proliferation
- drug release
- cell free
- case control
- prostate cancer
- young adults
- mesenchymal stem cells
- single molecule
- mass spectrometry
- bone marrow
- adverse drug
- nucleic acid