New SDS-Based Polyelectrolyte Multicore Nanocarriers for Paclitaxel Delivery-Synthesis, Characterization, and Activity against Breast Cancer Cells.
Marzena SzwedSylwia MichlewskaKatarzyna Dominika KaniaMarta SzczęchAgnieszka MarczakKrzysztof SzczepanowiczPublished in: Cells (2023)
The low distribution of hydrophobic anticancer drugs in patients is one of the biggest limitations during conventional chemotherapy. SDS-based polyelectrolyte multicore nanocarriers (NCs) prepared according to the layer by layer (LbL) procedure can release paclitaxel (PTX), and selectively kill cancer cells. Our main objective was to verify the antitumor properties of PTX-loaded NCs and to examine whether the drug encapsulated in these NCs retained its cytotoxic properties. The cytotoxicity of the prepared nanosystems was tested on MCF-7 and MDA-MB-231 tumour cells and the non-cancerous HMEC-1 cell line in vitro. Confocal microscopy, spectrophotometry, spectrofluorimetry, flow cytometry, and RT PCR techniques were used to define the typical hallmarks of apoptosis. It was demonstrated that PTX encapsulated in the tested NCs exhibited similar cytotoxicity to the free drug, especially in the triple negative breast cancer model. Moreover, SDS/PLL/PTX and SDS/PLL/PGA/PTX significantly reduced DNA synthesis. In addition, PTX-loaded NCs triggered apoptosis and upregulated the transcription of Bax, AIF, cytochrome-c, and caspase-3 mRNA. Our data demonstrate that these novel polyelectrolyte multicore NCs coated with PLL or PLL/PGA are good candidates for delivering PTX. Our discoveries have prominent implications for the possible choice of newly synthesized, SDS-based polyelectrolyte multicore NCs in different anticancer therapeutic applications.
Keyphrases
- cell cycle arrest
- breast cancer cells
- drug delivery
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- flow cytometry
- cancer therapy
- oxidative stress
- end stage renal disease
- ejection fraction
- pi k akt
- chronic kidney disease
- prognostic factors
- circulating tumor
- peritoneal dialysis
- squamous cell carcinoma
- cell free
- drug release
- nucleic acid