Development of Multifunctional Targeted Dual-Loaded Polymeric Nanoparticles for Triple-Negative Breast Cancer Treatment

<b>Background/Objectives</b>: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that accounts for 15-20% of all breast cancer cases. TNBC is very difficult to treat with conventional treatment modalities such as chemotherapy, radiotherapy, and surgery; <b>Methods</b>: In this study, we developed a dual-loaded targeted nanotherapeutics against TNBC to solve the challenging problems associated with TNBC treatment: lack of efficacy, toxicity, and poor site-specific drug delivery; PEGylated methacrylate-polylactide copolymer containing cisplatin was synthesized and characterized; <b>Results</b>: The copolymer was used to fabricate nanoparticles (NPs) in the presence of paclitaxel with 1.33% drug loading. The nanoparticles were homogenous, with an average particle size of 198 nm and a negative zeta potential (-41.3 mV). Cetuximab (CTX), a monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), was attached to the NP's surface to enhance the targetability to TNBC. In vitro studies including cell uptake and cytotoxicity in MDA-MB-231 cells confirmed that CTX-targeted NPs have the potential for treating TNBC. The IC₅₀ of CTX-NPs after 96 h of incubation was 0.1 μM, which was significantly lower than those of p-NPs (0.49 μM) and free drugs (PTX + cPt: 0.57 μM); <b>Conclusions</b>: In summary, this research shows that CTX-targeted polymeric NPs containing cisplatin and paclitaxel are effective in treating TNBC in vivo investigations are ongoing.