Despite the clinical benefits that chemotherapeutics has had on the treatment of breast cancer, drug resistance remains one of the main obstacles to curative cancer therapy. Nanomedicines allow therapeutics to be more targeted and effective, resulting in enhanced treatment success, reduced side effects, and the possibility of minimising drug resistance by the co-delivery of therapeutic agents. Porous silicon nanoparticles (pSiNPs) have been established as efficient vectors for drug delivery. Their high surface area makes them an ideal carrier for the administration of multiple therapeutics, providing the means to apply multiple attacks to the tumour. Moreover, immobilising targeting ligands on the pSiNP surface helps direct them selectively to cancer cells, thereby reducing harm to normal tissues. Here, we engineered breast cancer-targeted pSiNPs co-loaded with an anticancer drug and gold nanoclusters (AuNCs). AuNCs have the capacity to induce hyperthermia when exposed to a radiofrequency field. Using monolayer and 3D cell cultures, we demonstrate that the cell-killing efficacy of combined hyperthermia and chemotherapy via targeted pSiNPs is 1.5-fold higher than applying monotherapy and 3.5-fold higher compared to using a nontargeted system with combined therapeutics. The results not only demonstrate targeted pSiNPs as a successful nanocarrier for combination therapy but also confirm it as a versatile platform with the potential to be used for personalised medicine.

Australian Institute for Bioengineering and Nanotechnology Corner College and Cooper Rds The University of Queensland Brisbane QLD 4072 Australia

Centre of Polymer Systems Tomas Bata University 5678 760 01 Zlin Czech Republic

Commonwealth Scientific and Industrial Research Organization 343 Royal Parade Parkville VIC 3052 Australia

Department of Electrical and Computer Systems Engineering Monash University Clayton Campus Clayton VIC 3168 Australia

Melbourne Centre for Nanofabrication Victorian Node of the Australian National Fabrication Facility Clayton VIC 3168 Australia

Monash Centre for Electron Microscopy Clayton Campus Monash University Clayton VIC 3168 Australia

Monash Institute of Pharmacy and Pharmaceutical Sciences Monash University 381 Royal Parade Parkville VIC 3052 Australia

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