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Background Poly (β-amino Ester) nanocarriers show promise for gene therapy, but their effectiveness can be limited by the environment within the body. This study aims to understand how common cell culture media components affect optimized PBAE nanocarrier performance in gene delivery. Methods Optimized PBAE was synthesized based on Michael addition reaction and characterized by different assays, this study employed techniques like DLS and TEM to characterize PBAE nanocarriers, followed by cellular uptake analysis (flow cytometry and confocal imaging) and evaluation of gene expression under different polymer/DNA ratio ratios and media conditions. Results The nanocarriers exhibited size under 200 nm and surface positive charge, with high encapsulation efficiency (up to 95%). Cellular uptake, transfection efficiency, and cytotoxicity were evaluated. Flow cytometry analysis revealed high cellular uptake (over 77% at 1 hour and up to 95% after 3 hours) and good viability. Transfection efficiency reached up to 80% with 2 μg DNA, particularly at weight ratios of 60 and 90. Conclusion The study also identified factors affecting transfection efficiency, including serum concentration and antibiotics in the culture medium, highlighting the importance of optimizing these conditions for future applications. Plain Language Summary Our study focused on a new way to deliver medicine directly to cells using tiny particles called nanocarriers. These tiny particles are made from a special material called PBAE. Our study found that certain things around these nanocarriers, like antibiotics and high levels of a substance in the cell medium, can make it harder for the medicine to get into the cells. We also found that while the PBAE material is safe on its own, it can become more harmful when used in the nanocarriers at high amounts. By figuring out the best conditions for these nanocarriers, we hope to make gene therapy, a treatment for diseases like cancer, work better and be safer. GRAPHICAL ABSTRACT [ABSTRACT FROM AUTHOR]

A pH-sensitive shell-sheddable magnetic nanocarrier was prepared based on Fe3O4@SiO2 nanoparticles coated with polyethyleneimine (PEI) and polyethyleneglycol (PEG). The PEI was coated on Fe3O4@SiO2 nanoparticles through an electrostatic attraction and the PEG chains were connected to the PEI via pH-sensitive benzoicimine bonds. The synthesized products and final nanocarrier were characterized with FT-IR, 1H NMR, dynamic light scattering (DLS), zeta-potential, TEM, and vibrating sample magnetometer (VSM). The PEI, as a middle layer, was used to load the curcumin (an anticancer drug) via van der Waals interactions and the shedding of PEG as a hydrophilic corona at the tumor pH (acidic) could induce the release of the drug. The curcumin loading content was found to be ~15% and curcumin-loaded magnetic nanoparticles (C-LMNs) showed more triggered release at the tumor pH (5.6) than physiological pH (7.4). In comparison to pure magnetic nanoparticles (MNs), the C-LMNs showed more cytotoxicity to human prostate cancer cell (PC-3) and also resulted in an increased rate of late apoptotic/necrotic PC-3 cells, assessed by flow cytometry analysis. In conclusion, the C-LMN as pH- and magnetic responsive nano-carrier showed good potential for targeted curcumin delivery in therapy of prostate cancer. [ABSTRACT FROM AUTHOR]