Doxorubicin-loaded, charge reversible, folate modified HPMA copolymer conjugates for active cancer cell targeting

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin

“…23 CS-UA (100 mg) was dissolved in 30 mL of PBS (0.1 M, pH 8.5), and two equivalents of DMMA (157 mg) were slowly added; the pH of the solution was maintained at 8.0-8.5 by simultaneous addition of 0.2 M NaOH solution. The reaction was performed at room temperature for 6 h, and DA-CS-UA was obtained by lyophilization.…”

“…23 4T1 cells were seeded in 96-well plates (2,000 cells/well) and cultured for 24 h. The polymers or DOX formulations in different concentrations were subsequently added at pH 7.4 or 6.8 and incubated for 6 h. Later, the medium was replaced with a fresh one and incubated for another 18 h. The cell viability of each group was determined by MTT assay.…”

A smart polymeric platform for multistage nucleus-targeted anticancer drug delivery

“…In our study, R8NLS peptide was further modified with dimethylmaleic anhydride (DMA) to endow the conjugates with pH-sensitive chargereversal property. DMA is known to be a pH-reversible aminoprotecting reagent, and the modified amino groups can be regenerated at moderate mild acid microenvironment (pH6.5) of tumor tissue [26,27]. The pH-dependent cellular behavior of the DMAmodified conjugate (P-GFLG-R8NLS-DMA-FITC) was evaluated ( Fig.…”

Ligand-Tagged Cationic Liposome Facilitates Efficient Gene Delivery to Folate Receptors

“…Strategies to improve the efficiency and biocompatibility of cationic elements for gene delivery typically involve grafting the functional ligands, such as lipids, peptides and sugars or a combination thereof, to advance the stability, targeting, uptake and sub-cellular trafficking capabilities of the carrier 9 . The last few decades have witnessed ligand-modified nano-carriers being extensively studied in probing for a more specific targeting strategy for their potential clinical use in cancer therapy 10,11 . Targeted delivery has therefore attracted much attention in anticancer research due to advantages such as enhanced distribution in tumour sites and reduced side effects in normal tissues 12 .…”

“…Consequently, this may also diminish the water solubility of the carrier/ vector, thereby negatively influencing the release profile of the therapeutics and an undesirable increase in the phagocytosis by macrophages in the circulation. Conversely, we hypothesized that upon cell-membrane adhesion, which brings the conjugate in close proximity to the cell surface, the chance for folate to interact with FR might also increase, leading to a synergic enhancing effect on cellular uptake by both ligand receptor interaction and electronic attraction 11 . In a study by Valencia et al 15 only 20% of the folate from PLGA-PEG-folate was present on the NP surface, while the rest remained presumably buried in the PLGA NP core due to hydrophobic interactions of PLGA and folate.…”