Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer

Abstract

Gemcitabine has long been the standard of care for treating pancreatic ductal adenocarcinoma (PDAC), despite its poor pharmacokinetics/dynamics and rapid development of drug resistance. In this study, we have developed a novel nanoparticle platform based on nanoscale coordination polymer-1 (NCP-1) for simultaneous delivery of two chemotherapeutics, oxaliplatin and gemcitabine monophosphate (GMP), at 30 wt.% and 12 wt.% drug loadings, respectively. A strong synergistic therapeutic effect of oxaliplatin and GMP was observed in vitro against AsPc-1 and BxPc-3 pancreatic cancer cells. NCP-1 particles effectively avoid uptake by the mononuclear phagocyte system (MPS) in vivo with a long blood circulation half-life of 10.1±3.3 h, and potently inhibit tumor growth when compared to NCP particles carrying oxaliplatin or GMP alone. Our findings demonstrate NCP-1 as a novel nanocarrier for the co-delivery of two chemotherapeutics that have distinctive mechanisms of action to simultaneously disrupt multiple anticancer pathways with maximal therapeutic efficacy and minimal side effects.

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…The nanoparticles demonstrated enhanced in vitro toxicity compared to the coadministration of the free drugs in HL60, MCF7, and MDA-MB-231 cancer cells. A nanoscale coordination polymer, constructed through self-assembly processes of polydentate bridging ligands and metal ions/clusters, was recently used as a novel carrier to co-deliver oxaliplatin (30 wt.%) and gemcitabine (12 wt.%) [158]. The combination therapy demonstrated enhanced antitumor efficacy in human pancreatic ductal adenocarcinoma xenograft mouse models, with the NPs exhibiting biodegradability, low toxicity, and long blood circulation half-lives.…”

“…4. Various nanoformulations for co-delivery of therapeutics with normalized pharmacokinetics and pharmacodynamics, including self-assembled nanoscale coordination polymer [158], cholesterol-based chimeric nanoparticle [157], thermosensitive hydrogel [123], mesoporous silica nanoparticle [125], and liposomes [124].…”

Hyaluronic Acid Engineered Nanomicelles Loaded with 3,4-Difluorobenzylidene Curcumin for Targeted Killing of CD44+ Stem-Like Pancreatic Cancer Cells

“…Upon diagnosis, 80 % of pancreatic cancer cases are deemed inoperable due to the high risk of tumor infiltration with surrounding blood vessels and digestive ducts [3][4][5] . Due to the complex nature of malignant pancreatic cancers the incidence and death rates have been increasing although the overall cancer incidence and death rates are declining for other cancers 6 .…”

Redox poly(ethylene glycol)-b-poly(l-lactide) micelles containing diselenide bonds for effective drug delivery

“…However, due to the drug resistance of cancer cells, nonspecific adsorption in circulation and so on, chemotherapy is usually accompanied by the serious side effects and low drug bioavailability [1][2][3]. In the past decades, stimuli-responsive amphiphilic polymers have attracted much attention in drug delivery, and a series of pH-, CO 2 À , temperature-and light-stimuli polymers have already been synthesized and realized the controlled release of the encapsulated drugs [4][5][6][7].…”