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Triple-Negative Breast Cancer Aptamer-Targeting Porous Silicon Nanocarrier
Ankit Malhotra1, Pouya Dehghankelishadi1, Ishdeep Kaur1
1Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Abstract:
Common treatment approaches for triple-negative breast cancer (TNBC) are associated with severe side effects due to the unfavorable biodistribution profile of potent chemotherapeutics. Here, we explored the potential of TNBC-targeting aptamer-decorated porous silicon nanoparticles (pSiNPs) as targeted nanocarriers for TNBC. A "salt-aging" strategy was employed to fabricate a TNBC-targeting aptamer functionalized pSiNP that was highly colloidally stable. Doxorubicin (Dox) was efficiently loaded into nanoparticles (179 ± 5 μg/mg of pSiNP) and experienced pH-dependent release kinetics. Further experiments highlighted that clathrin-mediated endocytosis was the primary route that aptamer-pSiNP conjugates take to enter the endolysosomal compartment of the MCF10Ca1h TNBC cells. A time-interval colocalization study shows the accumulation of an aptamer-decorated pSiNP conjugate in the lysosomes of TNBC cells, unlike for antibody-decorated pSiNPs, leading to particle-induced lysosomal swelling and membrane destabilization. Dox-loaded aptamer-pSiNPs efficiently reduced the viability of the TNBC cells (11.8 ± 1.5%) compared to nontargeted nanoparticles (58.2 ± 8.8%) while the developed system showed a low level of toxicity in healthy cells, both in vitro and in vivo. These findings have laid the foundation for further investigating the potential of aptamer-pSiNP conjugates as a targeted treatment strategy in preclinical TNBC models.
Insights
New aptamer-decorated porous silicon nanoparticles (pSiNPs) offer targeted delivery for triple-negative breast cancer (TNBC) chemotherapy. This approach reduces side effects by concentrating treatment in cancer cells, showing promise for improved TNBC therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) treatments face challenges due to severe side effects from chemotherapeutic biodistribution.
- Targeted nanocarriers are needed to improve drug delivery and minimize toxicity in TNBC therapy.
Purpose of the Study:
- To develop and evaluate aptamer-decorated porous silicon nanoparticles (pSiNPs) as targeted nanocarriers for TNBC treatment.
- To investigate the cellular uptake mechanism and therapeutic efficacy of these targeted pSiNPs loaded with doxorubicin (Dox).
Main Methods:
- Fabrication of TNBC-targeting aptamer-functionalized pSiNPs using a "salt-aging" strategy.
- Loading of doxorubicin (Dox) into pSiNPs and assessment of pH-dependent release kinetics.
- Investigation of cellular uptake via clathrin-mediated endocytosis and colocalization studies in MCF10Ca1h TNBC cells.
Main Results:
- Aptamer-pSiNP conjugates demonstrated high colloidal stability and efficient Dox loading (179 ± 5 μg/mg).
- Targeted pSiNPs accumulated in TNBC cell lysosomes, causing swelling and membrane destabilization.
- Dox-loaded aptamer-pSiNPs significantly reduced TNBC cell viability (11.8 ± 1.5%) with low toxicity to healthy cells in vitro and in vivo.
Conclusions:
- Aptamer-decorated pSiNPs represent a promising targeted delivery system for TNBC chemotherapy.
- The developed nanocarrier system effectively targets TNBC cells, enhances drug efficacy, and minimizes systemic toxicity.
- Further preclinical investigation of aptamer-pSiNP conjugates for TNBC treatment is warranted.
