αvβ3 integrin aptamer functionalized pH-responsive lipid polymer hybrid nanoparticles for targeted co-delivery of
Mahavir Narwade1, Niladri Haldar2, Rajkumar Samanta2
1Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth, Pune, India.
Abstract:
Triple-negative breast cancer (TNBC) is the deadliest type due to its aggressive behavior, high recurrence, metastatic, and mortality rates. This study was aimed at the targeted co-delivery of paclitaxel (PTX) and tamoxifen (TMF) via lipid polymer hybrid nanoparticles (LPHNPs) for treating TNBC. Here, we conjugated αvβ3 integrin aptamer over LPHNPs for targeting TNBC cells. The aptamer-conjugated LPHNPs showed significantly higher uptake in 4 T1 cells than non-targeted LPHNPs. The PTX + TMX co-loaded targeted LPHNPs have cell viabilities of 5.9 ± 0.7 and 7.8 ± 0.6 % in 4 T1 and MDA-MB-231 cells, respectively, in 48 h. The cell viabilities of PTX + TMX co-loaded non-targeted LPHNPs and free PTX + TMX were 17.27 ± 1.56 and 24.31 ± 0.81 % in 4 T1 cells and 16.07 ± 0.14 and 20.15 ± 1.11 % in MDA-MB-231 cells, respectively, in 48 h. Flow cytometry indicated that targeted LPHNP-mediated PTX + TMF delivery was considerably more efficient (~31 %) in inducing apoptosis than PTX + TMF co-loaded non-targeted LPHNPs (~21 %) and free PTX + TMF (~13 %). The anti-cancer efficiency was better when PTX and TMF were delivered together rather than separately. The cytotoxicity assessment in the 3D cell culture demonstrated higher anti-cancer effectiveness of aptamer-conjugated co-loaded LPHNPs, confirmed by significantly inducing cell death. Thus, the results concluded that PTX and TMF-loaded αvβ3 integrin aptamer conjugated LPHNPs have tremendous potential for treating TNBC.
Insights
Targeted lipid polymer hybrid nanoparticles co-delivering paclitaxel and tamoxifen show promise for treating triple-negative breast cancer (TNBC). This aptamer-conjugated nanoparticle system enhances drug delivery and induces significant cancer cell death.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and high mortality rates.
- Current treatment strategies for TNBC often face limitations related to efficacy and side effects.
Purpose of the Study:
- To develop targeted lipid polymer hybrid nanoparticles (LPHNPs) for the co-delivery of paclitaxel (PTX) and tamoxifen (TMF).
- To enhance the therapeutic efficacy of PTX and TMF against TNBC through targeted delivery using αvβ3 integrin aptamer conjugation.
Main Methods:
- Conjugation of αvβ3 integrin aptamer to LPHNPs for specific targeting of TNBC cells.
- Co-loading of paclitaxel (PTX) and tamoxifen (TMF) into the aptamer-conjugated LPHNPs.
- Evaluation of cellular uptake, cytotoxicity, and apoptosis induction in TNBC cell lines (4T1 and MDA-MB-231) and 3D cell cultures.
Main Results:
- Aptamer-conjugated LPHNPs demonstrated significantly higher uptake in TNBC cells compared to non-targeted LPHNPs.
- Co-loaded targeted LPHNPs significantly reduced cell viability (e.g., 5.9% in 4T1 cells) compared to non-targeted LPHNPs and free drugs.
- Targeted LPHNP delivery substantially increased apoptosis induction (~31%) compared to non-targeted LPHNPs (~21%) and free drugs (~13%).
Conclusions:
- Aptamer-conjugated LPHNPs effectively co-deliver PTX and TMF, showing enhanced anti-cancer efficacy against TNBC.
- This targeted nanoparticle system holds significant potential as a novel therapeutic strategy for treating triple-negative breast cancer.
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