Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma

Abstract

Due to the critical correlation between inflammation and carcinogenesis, a therapeutic candidate with anti-inflammatory activity may find application in cancer therapy. Here, we report the therapeutic efficacy of celastrol as a promising candidate compound for treatment of pancreatic carcinoma via naïve neutrophil membrane-coated poly(ethylene glycol) methyl ether- block -poly(lactic- co -glycolic acid) (PEG-PLGA) nanoparticles. Neutrophil membrane-coated nanoparticles (NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery in vivo . Using tumor-bearing mice xenograft model, NNPs showed selective accumulations at the tumor site following systemic administration as compared to nanoparticles without neutrophil membrane coating. In both orthotopic and ectopic tumor models, celastrol-loaded NNPs demonstrated greatly enhanced tumor inhibition which significantly prolonged the survival of tumor bearing mice and minimizing liver metastases. Overall, these results suggest that celastrol-loaded NNPs represent a viable and effective treatment option for pancreatic carcinoma.

Cell-mediated and cell membrane-coated nanoparticles for drug delivery and cancer therapy

“…Cell membrane-coated NP (CMCNPs) have been increasingly studied for their mimicry of cell surface functionality, which can aid in reducing the immune responses of synthetic NPs in vivo and introduce the ability to combine both natural and synthetic materials concisely as shown in Figure 1. Celland cell membrane-based drug carriers exhibiting intrinsic properties of in vivo biology have been shown to overcome the challenges faced by synthetic NP-based drug carriers and achieve acceptable toxicity and better biocompatibility than their synthetic counterparts [7][8][9][10][11][12] . Major advantages of using cell-and cell membrane-based drug carriers include provision of immune escape and specific tumor targeting imparted by the cell membrane proteins leading to improved EPR in cancer therapies, and an ability to generate desired cytotoxic immunomodulatory effects via cell surface engineering, leading to tumor regression [13][14][15][16][17][18] .…”

<p>Paclitaxel-Loaded Macrophage Membrane Camouflaged Albumin Nanoparticles for Targeted Cancer Therapy</p>

“…Cell-cycle distributions were assessed by propidium iodide (PI) staining as described in previous studies. 38 Briefly, B16F10 cells were seeded in six-well plates at 3 × 10 5 cells per well and incubated for 48 hrs at 37°C. Cells were then incubated with 2 mL of medium containing different concentrations of Taxol, ANPs/PTX, and RANPs/PTX for another 24 hrs.…”

Nano drug delivery systems in upper gastrointestinal cancer therapy

“…The proteolytic-enzyme complex encapsulated in a liposome cleaves excessive extracellular matrix and facilitates drug invasion. Meanwhile, PEG-PLGA NPs coated with neutrophil membranes were shown to overcome the blood-pancreas barrier and actively accumulate in cancerous tissue of a mouse model [ 140 ]. The bio-mimicking nanocarriers were loaded with celastrol, a pentacyclic triterpenoid extracted from Tripterygium wilfordii .…”