Lipid-Nanoparticle-Mediated Delivery of Docetaxel Prodrug for Exploiting Full Potential of Gold Nanoparticles in the Treatment of Pancreatic Cancer

Abstract

Current chemoradiation therapy suffers from normal tissue toxicity. Thus, we are proposing incorporating gold nanoparticles (GNPs) and docetaxel (DTX), as they have shown very promising synergetic radiosensitization effects. Here, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNPDTX-P) on GNP uptake in pancreatic cancer models in vitro and in vivo. For the in vitro experiment, a pancreatic cancer cell line, MIA PaCa-2, was cultured and dosed with 1 nM GNPs and 45 nM free DTX or an equivalent dose of LNPDTX-P. For the in vivo experiment, MIA PaCa-2 cells were implanted subcutaneously in NRG mice, and the mice were dosed with 2 mg/kg of GNPs and 6 mg/kg of DTX or an equivalent dose of LNPDTX-P. The results show that LNPDTX-P-treated tumour samples had double the amount GNPs compared to control samples, both in vitro and in vivo. The results are very promising, as LNPDTX-P have superior targeting of tumour tissues compared to free DTX due to their nanosize and their ability to be functionalized. Because of their minimal toxicity to normal tissues, both GNPs and LNPDTX-P could be ideal radiosensitization candidates in radiotherapy and would produce very promising synergistic therapeutic outcomes.

cRGD-Conjugated GdIO Nanoclusters for the Theranostics of Pancreatic Cancer through the Combination of T1–T2 Dual-Modal MRI and DTX Delivery

“…Intracellular cRGD-GdIO-DTX can release DTX. Then, it can impede cell division and arrest cells in G2/M phase, resulting in cancer cell death [ 46 ]. As shown in Figure 7 a,b, the therapeutic effect of cRGD-GdIO-DTX was assessed using SW1990 and Panc-1 cells.…”

Therapeutic Approaches in Pancreatic Cancer: Recent Updates

“…Dextran-coated maghemite nanoparticles (56 μg/mL) exposure reduced ~50% of PANC-1 cell viability after 72 h incubation via alteration in expressions of heat shock proteins (HSPs) and p53 protein [ 67 ]. Lipid nanoparticles (LNP DTX-P ) on gold nanoparticles with docetaxel prodrug showed enhancement in the uptake of nanoparticles up to 2.8-folds by MIA PACA-2 cells than the controls [ 68 ]. In vitro assay, MIA PACA-2 cells proliferation IC 50 of 9.8 nM for LNP DTX noted against only docetaxel prodrug (44.4 nM).…”

“…In mechanism, nanoparticles containing cancerous cells cannot divide and are trapped in the M phase. Hence, LNP DTX-P on gold nanoparticles can be potentially employed for radiotherapy-based pancreatic cancer treatments [ 68 ]. The combined approach of using magnetic nanoparticles and hyperthermia against BxPC3 pancreatic tumor cells proved beneficial over nanoparticles only [ 69 ].…”

Responsive Nanomaterial Delivery Systems for Pancreatic Cancer Management

“…[180][181][182] In this context, a variety of pH-sensitive materials have been explored for the delivery of a range of therapeutic agents, including chemotherapy, peptide-based therapy, and genetic therapy. [182][183][184][185] In many cases, these are bound to the NP shell using pHresponsive linkers, some of which are mentioned in Figure 4. [131] Various studies have focused on developing pH-responsive NPs for targeted drug delivery in pancreatic cancer.…”