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Introduction
Marion Paolini currently works at the Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology. Marion does research in Cell Biology, Cancer Research and Biotechnology.
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Publications
Publications (22)
Introduction: Most nanomedicines are currently limited in their efficacy due to a sub-optimal biodistribution/accumulation in the target tissues. A large part of the administered dose remains useless due to the high rate of clearance by the mononuclear phagocytic system (mainly by Kupffer cells in liver). We designed a new approach based on the use...
Despite tremendous interest in gene therapies, the systemic delivery of nucleic acids still faces substantial challenges. To successfully administer nucleic acids, one approach is to encapsulate them in lipid nanoparticles (LNPs). However, LNPs administered intravenously substantially accumulate in the liver where they are taken up by the reticuloe...
Introduction: To efficiently deliver treatment, nanomedicines must exhibit sufficient blood bioavailability for further accumulation at the target site. So far, a large part of the administered dose remains useless due to the high rate of clearance by the mononuclear phagocytic system (mainly by Kupffer cells). Here we propose a new approach to red...
Introduction: To efficiently deliver treatment, nanomedicines must exhibit sufficient blood bioavailability for further accumulation at the target site. So far, a large part of the administered dose remains useless due to the high rate of clearance by the mononuclear phagocytic system (mainly by Kupffer cells). Here we propose a new approach to red...
Given its potential for high-resolution, customizable, and waste-free fabrication of medical devices and in vitro biological models, 3-dimensional (3D) bioprinting has broad utility within the biomaterials field. Indeed, 3D bioprinting has to date been successfully used for the development of drug delivery systems, the recapitulation of hard biolog...
Developing strategies to deliver the required dose of therapeutics into target tissues and cell populations within the body is a principal aim of controlled release and drug delivery. Specifically, there is an interest in developing formulations that can achieve drug concentrations within the therapeutic window, for extended periods of time, with t...
Many therapeutic agents offer a low useful dose (dose responsible for efficacy)/useless dose (dose eliminated or responsible for toxicity) ratio, mainly due to the fact that therapeutic agents must ensure in one single object all the functions required to deliver the treatment, which leads to compromises in their physico-chemical design. Here we in...
The development of new material platforms can improve our ability to study biological processes. Here, we developed a water‐compatible variant of a "click"‐like polymerization between alkynoates and secondary amines to form B‐aminoacrylate synthetic polyethylene glycol (PEG) based hydrogels. These materials are easy to access ‐ PEG alkynoate was sy...
The development of new material platforms can improve our ability to study biological processes. Here, we developed a water‐compatible variant of a "click"‐like polymerization between alkynoates and secondary amines to form B‐aminoacrylate synthetic polyethylene glycol (PEG) based hydrogels. These materials are easy to access ‐ PEG alkynoate was sy...
Introduction: The benefit of a nanomedicine is due to its bioavailability, its intrinsic efficacy balanced with its toxicity profile. The nanomedicine should exhibit sufficient blood bioavailability for efficient accumulation at the target site. So far, a large part of the administered dose remains useless due to the high rate of clearance by the m...
(A) Schematic representation of the nanocarriers and synthesis process of (B) PS80 micelles, (C) DSPE-PEG micelles, (D) PLGA nanoparticles and (E) HA nanoparticles.
Abbreviations: DSPE-PEG, 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(carboxy(polyethylene glycol)-2000); EDC, 1-ethyl-3-(3-dimethlyaminopropyl) carbodiimide; HA, hyaluronic acid;...
Favored intake of coated nanoparticles by HepaRG cells seen with Zeiss LSM710 confocal microscope with fixed optical parameters after 20 minutes (A, B), 3 hours (C, D) or 24 hours (E, F) of in vitro incubation of coated PLGA-Ga nanoparticles (A, C, E) or uncoated PLGA nanoparticles (B, D, F).
Notes: Fixed cells were imaged on a Zeiss confocal LSM71...
In vivo imaging of a mouse injected with DilC18 in H2O-EtOH (1:1 v/v).
Notes: Presented images were taken 1 minute, 5 minutes, 30 minutes and 60 minutes after intravenous injection in the tail vein. Scale: min =7.00E7; max =2.00E8 radiant efficiency in (p/second/cm2/sr)/(µW/cm2).
Abbreviations: DilC18, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodica...
In vitro control of MDA-MB-231 cells sensitization to docetaxel by BM.
Notes: Cell sensitization to docetaxel diluted in NaCl 1% (1:9 v/v) prior to injection was measured using a WST-1 assay according to the manufacturer’s instructions, after 48 hours of co-incubation of BM (0–5 µM) and docetaxel (0–25 nM) in cell culture medium. A statistical anal...
Schematic representation of the functionalization of PLGA nanoparticles with galactosamine.
Abbreviations: BM, bergamottin; EDC, 1-ethyl-3-(3-dimethlyaminopropyl) carbodiimide; NHS, N-hydroxysulfosuccinimide; PLGA, poly(lactic-co-glycolic) acid.
In vivo imaging of mice injected with (A) PS80–EtOH DilC18, (B) DSPE-PEG DilC18, (C) DSPE-PEG lactosyl DilC18, (D) HA DilC18, (E) PLGA DilC18 and (F) PLGA-Ga DilC18.
Notes: Presented images were taken approximately every 2 minutes until 15 minutes, every 4 minutes from 15 minutes to 30 minutes and every 7 minutes from 30 minutes to 1 hour. At least...
In vivo imaging of mice injected with (A) HA DilC18, (B) PLGA DilC18 and (C) PLGA-Ga DilC18, at lowered concentration of nanoparticles (0.25 g/L of polymer).
Notes: Presented images were taken approximately every 2 minutes until 15 minutes, every 4 minutes from 15 minutes to 30 minutes and every 7 minutes from 30 minutes to 1 hour. At least three m...
In vitro uptake of nanoparticles by HepaRG cells seen with confocal microscope (Zeiss LSM710) using the 63× objective in oil.
Notes: Uptake of (A) coated DSPE-PEG micelles with lactosyl containing 27 mg/L of DilC18 and (B) uncoated DSPE-PEG micelles containing 27 mg/L of DilC18 after 3 hours of in vitro incubation on HepaRG cells. Images were acqui...
Relative mean weight evolution per treatment group, relative to the mean weight per group at the first day of injection, ±SD.
Notes: No difference in weight evolution was noted between treated groups. No significant weight loss was observed.
Abbreviations: BM, bergamottin; EtOH, ethanol; PLGA, poly(lactic-co-glycolic) acid; PLGA-Ga, PLGA nanopartic...
Most drugs are metabolized by hepatic cytochrome P450 3A4 (CYP3A4), resulting in their reduced bioavailability. In this study, we present the design and evaluation of bio-compatible nanocarriers trapping a natural CYP3A4-inhibiting compound. Our aim in using nanocarriers was to target the natural CYP3A4-inhibiting agent to hepatic CYP3A4 and leave...
Nanomedicines are mainly used as drug delivery systems; here we evaluate a new application - to inhibit a drug's metabolism thereby enhancing its effective dose. Micelles containing the natural furanocoumarin 6′,7′-dihydroxybergamottin (DHB), a known CYP450 inhibitor, were developed to transiently block hepatic CYP450-mediated drug metabolism and i...