Abstract
In this study we have developed biodegradable polymeric nanoparticles (NPs) containing the cytostatic drugs mertansine (MRT) or cabazitaxel (CBZ). The NPs are based on chitosan (CS) conjugate polymers synthesized with different amounts of the photosensitizer tetraphenylchlorin (TPC). These TPC–CS NPs have high loading capacity and strong drug retention due to π–π stacking interactions between the drugs and the aromatic photosensitizer groups of the polymers. CS polymers with 10% of the side chains containing TPC were found to be optimal in terms of drug loading capacity and NP stability. The TPC–CS NPs loaded with MRT or CBZ displayed higher cytotoxicity than the free form of these drugs in the breast cancer cell lines MDA-MB-231 and MDA-MB-468. Furthermore, light-induced photochemical activation of the NPs elicited a strong photodynamic therapy effect on these breast cancer cells. Biodistribution studies in mice showed that most of the TPC–CS NPs accumulated in liver and lungs, but they were also found to be localized in tumors derived from HCT-116 cells. These data suggest that the drug-loaded TPC–CS NPs have a potential in combinatory anticancer therapy and as contrast agents.
Highlights
Cancer treatment by chemotherapy and radiotherapy still suffers from systemic toxicity, drug resistance, and low selectivity leading to an unsatisfactory outcome
Porphyrins have been used as theranostic agents in cancer treatment for photodynamic therapy (PDT), photochemical internalization (PCI),[2] photothermal therapy,[3] sonodynamic therapy,[4] radiotherapy,[5] for diagnostic fluorescent imaging, magnetic resonance imaging,[6] and photoacoustic imaging.[7]
We suggest that efficient GPX4 inhibitors, such as RSL3 or FINO2,37,38 could be used in a clinical setting in order to elicit a more efficient PDT effect by sensitizing the cancer cells to undergo ferroptosis. 3.6
Summary
Cancer treatment by chemotherapy and radiotherapy still suffers from systemic toxicity, drug resistance, and low selectivity leading to an unsatisfactory outcome. Nanoparticles (NPs) have been widely used to load diagnostic and therapeutic agents, and one can benefit from their ability to target into tumors via passive accumulation and active targeting approaches. Multimodal and theranostic NPs combining treatment strategies and diagnostic imaging have attracted huge interest.[1] Porphyrins have been used as theranostic agents in cancer treatment for photodynamic therapy (PDT), photochemical internalization (PCI),[2] photothermal therapy,[3] sonodynamic therapy,[4] radiotherapy,[5] for diagnostic fluorescent imaging, magnetic resonance imaging,[6] and photoacoustic imaging.[7] Most porphyrins designed as therapeutic agents are hydrophobic and form aggregates in aqueous solution. Porphyrins have been incorporated into NPs to make them more suitable for tissue delivery.[8,9]
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