TY - JOUR
T1 - Combination of chemotherapy and mild hyperthermia using targeted nanoparticles
T2 - A potential treatment modality for breast cancer
AU - Kaur, Ishdeep
AU - Tieu, Terence
AU - Deepagan, Veerasikku G.
AU - Ali, Muhammad A.
AU - Alsunaydih, Fahad
AU - Rudd, David
AU - Moghaddam, Maliheh A.
AU - Bourgeois, Laure
AU - Adams, Timothy E.
AU - Thurecht, Kristofer J.
AU - Yuce, Mehmet
AU - Cifuentes-Rius, Anna
AU - Voelcker, Nicolas H.
N1 - Funding Information:
A.C-R. was supported by the National Health and Medical Research Council (NHMRC) of Australia (GNT1112432).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/4/30
Y1 - 2023/4/30
N2 - 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.
AB - 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.
KW - breast cancer
KW - combination therapy
KW - drug delivery
KW - hyperthermia
KW - porous silicon nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85160659645&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics15051389
DO - 10.3390/pharmaceutics15051389
M3 - Article
C2 - 37242631
AN - SCOPUS:85160659645
SN - 1999-4923
VL - 15
JO - Pharmaceutics
JF - Pharmaceutics
IS - 5
M1 - 1389
ER -