Optimizing photo-assisted eradication of triple-negative breast cancer through novel doped conjugated polymer nanoparticles

IBARRA L.E.; CAMORANI S.; AGNELLO L.; CHESTA C.; PALACIOS R.E.; D'ARGENIO A.; NILO R.; ZANETTI A.; FEDELE M.; CERCHIA L.

Sevilla

Congreso; 28TH CONGRESS OF THE EUROPEAN ASSOCIATION FOR CANCER RESEARCH; 2022

EUROPEAN ASSOCIATION FOR CANCER RESEARCH

IntroductionTriple-negative breast cancer (TNBC) has a poor prognosis because of the aggressive clinical behavior and limited targeted treatment options. In recent years Photodynamic therapy (PDT) has been examined experimentally in TNBC and it has been proposed as a therapeutic option to bypass and inhibit escape pathways in multidrug resistant breast cancer cells. Here, we investigated the tumor targeting and the antitumorigenic effectiveness of novel photosensitizers-based on conjugated-polymers-nanoparticles (CPNs) whose cancer selectivity is ensured by the conjugation to novel RNA aptamers recognizing human TNBC cells at high efficiency.Material and MethodsWe prepared CPNs by using the CP F8BT due to its exceptional features as a donor antenna to collect excitation energy and funnel it towards molecular dopant PS acceptors, such as the porphyrin PtOEP. Two functional polystyrene-based polymers (PS-PEG-COOH and PSMA) were chosen and incorporated in ~ 20% mass ratio to F8BT mass in order to improve colloidal stability and introduce COOH groups on the surface of CPNs for EDC reaction with NH2-modified aptamers (the previously validated anti-EGFR CL4 and the recently optimized sTN58 and sTN29 aptamers). Aptamer-decorated CPNs were characterized by size and zeta potential by DLS. Cell targeting/uptake, citotoxicity and photodynamic evaluation of the nanovectors were tested in TNBC cells and cisplatin-resistant derivatives.Results and DiscussionsOur results show the selectivity of recognition for TNBC membrane receptors and cell uptake of doped conjugated PNPs decorated with CL4, sTN58 or sTN29 aptamer in different TNBC cells. A significant improvement in PDT efficacy was obtained in the presence of CPNs functionalized with the aptamer compared to CPNs unconjugated or scrambled aptamer-conjugated. In cisplatin-resistant cells, sTN58 was the best candidate for improving labelling and PDT efficacy with CPNs. We propose sTN58, sTN29 and CL4 aptamers as valuable tools for selective TNBC cell internalization and therapeutic improvements for CPNs in PDT protocols.ConclusionOur study proposes novel and safe photosensitizers-loaded and aptamer-decorated nanosystems with excellent potential for the application in TNBC therapy. The availability of a panel of TNBC cell-type targeting aptamers, will supply multiple tumor-targeting agents with the possibility of using them in different combinations depending on distinct molecular and/or clinical TNBC phenotypes.