Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related mortality inthe Western world and is envisaged to become the second cause by 2030. Although our knowledgeabout the molecular biology of PDAC is continuously increasing, this progress has not been translatedinto better patients’ outcome. Liposomes have been used to circumvent concerns associated withthe low efficiency of anticancer drugs such as severe side effects and damage of healthy tissues,but they have not resulted in improved efficacy as yet. Recently, the concept is emerging thatthe limited success of liposomal drugs in clinical practice is due to our poor knowledge of thenano–bio interactions experienced by liposomes in vivo. After systemic administration, lipid vesiclesare covered by plasma proteins forming a biomolecular coating, referred to as the protein corona(PC). Recent studies have clarified that just a minor fraction of the hundreds of bound plasmaproteins, referred to as “PC fingerprints” (PCFs), enhance liposome association with cancer cells,triggering efficient particle internalization. In this study, we synthesized a library of 10 liposomalformulations with systematic changes in lipid composition and exposed them to human plasma(HP). Size, zeta-potential, and corona composition of the resulting liposome–protein complexes werethoroughly characterized by dynamic light scattering (DLS), micro-electrophoresis, and nano-liquidchromatography tandem mass spectrometry (nano-LC MS/MS). According to the recent literature,enrichment in PCFs was used to predict the targeting ability of synthesized liposomal formulations.Here we show that the predicted targeting capability of liposome–protein complexes clearly correlatewith cellular uptake in pancreatic adenocarcinoma (PANC-1) and insulinoma (INS-1) cells asquantified by flow-assisted cell sorting (FACS). Of note, cellular uptake of the liposomal formulationwith the highest abundance of PCFs was much larger than that of Onivyde®, an Irinotecan liposomaldrug approved by the Food and Drug Administration in 2015 for the treatment of metastatic PDAC.Given the urgent need of efficient nanocarriers for the treatment of PDAC, we envision that ourresults will pave the way for the development of more efficient PC-based targeted nanomaterials.Here we also show that some BCs are enriched with plasma proteins that are associated with theonset and progression of PDAC (e.g., sex hormone-binding globulin, Ficolin-3, plasma protease C1inhibitor, etc.). This could open the intriguing possibility to identify novel biomarkers.
Protein corona fingerprints of liposomes: new opportunities for targeted drug delivery and early detection in pancreatic cancer
Caputo D;Coppola R;
2019-01-01
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related mortality inthe Western world and is envisaged to become the second cause by 2030. Although our knowledgeabout the molecular biology of PDAC is continuously increasing, this progress has not been translatedinto better patients’ outcome. Liposomes have been used to circumvent concerns associated withthe low efficiency of anticancer drugs such as severe side effects and damage of healthy tissues,but they have not resulted in improved efficacy as yet. Recently, the concept is emerging thatthe limited success of liposomal drugs in clinical practice is due to our poor knowledge of thenano–bio interactions experienced by liposomes in vivo. After systemic administration, lipid vesiclesare covered by plasma proteins forming a biomolecular coating, referred to as the protein corona(PC). Recent studies have clarified that just a minor fraction of the hundreds of bound plasmaproteins, referred to as “PC fingerprints” (PCFs), enhance liposome association with cancer cells,triggering efficient particle internalization. In this study, we synthesized a library of 10 liposomalformulations with systematic changes in lipid composition and exposed them to human plasma(HP). Size, zeta-potential, and corona composition of the resulting liposome–protein complexes werethoroughly characterized by dynamic light scattering (DLS), micro-electrophoresis, and nano-liquidchromatography tandem mass spectrometry (nano-LC MS/MS). According to the recent literature,enrichment in PCFs was used to predict the targeting ability of synthesized liposomal formulations.Here we show that the predicted targeting capability of liposome–protein complexes clearly correlatewith cellular uptake in pancreatic adenocarcinoma (PANC-1) and insulinoma (INS-1) cells asquantified by flow-assisted cell sorting (FACS). Of note, cellular uptake of the liposomal formulationwith the highest abundance of PCFs was much larger than that of Onivyde®, an Irinotecan liposomaldrug approved by the Food and Drug Administration in 2015 for the treatment of metastatic PDAC.Given the urgent need of efficient nanocarriers for the treatment of PDAC, we envision that ourresults will pave the way for the development of more efficient PC-based targeted nanomaterials.Here we also show that some BCs are enriched with plasma proteins that are associated with theonset and progression of PDAC (e.g., sex hormone-binding globulin, Ficolin-3, plasma protease C1inhibitor, etc.). This could open the intriguing possibility to identify novel biomarkers.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
