Fluorinated-PLGA Nanoparticles for Enhanced Drug Encapsulation and 19F-NMR Detection.

In the continuous search to develop multimodal systems with combined diagnostic and therapeutic functions, several efforts have been focused on the development of multifunctional drug delivery systems. Herein we designed, by a covalent approach, a novel class of fluorinated poly(lactic-co-glycolic acid) co-polymers (F-PLGA) containing an increasing number of magnetically equivalent fluorine atoms. In particular, two novel compounds, F 3 -PLGA and F 9 -PLGA, were synthesized and their chemical structure and thermal stability were analysed by solution NMR, DSC, and TGA. The obtained F-PLGA compounds were proved to form in aqueous solution colloidal stable nanoparticles (NPs) displaying a strong 19 F-NMR signal. The fluorinated NPs also showed an enhanced ability to load hydrophobic drugs containing fluorine atoms with respect to analogue pristine PLGA NPs. Preliminary in vitro studies showed their cellular availability and ability to intracellularly deliver and release a functioning drug.

[1]  S. Alcântara,et al.  Low-fouling Fluoropolymers for Bioconjugation and In Vivo Tracking. , 2020, Angewandte Chemie.

[2]  R. Simonutti,et al.  The effect of cationic groups on the stability of 19 F MRI contrast agents in nanoparticles , 2019, Journal of Polymer Science Part A: Polymer Chemistry.

[3]  S. Laurent,et al.  Fluorinated MRI contrast agents and their versatile applications in the biomedical field. , 2019, Future medicinal chemistry.

[4]  C. Zhang,et al.  Fluorinated Glycopolymers as Reduction-responsive 19F MRI Agents for Targeted Imaging of Cancer. , 2019, Biomacromolecules.

[5]  G. Comi,et al.  Multispectral MRI with Dual Fluorinated Probes to Track Mononuclear Cell Activity in Mice. , 2019, Radiology.

[6]  C. D. de Korte,et al.  Multicore Liquid Perfluorocarbon‐Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking , 2019, Advanced functional materials.

[7]  Shizhen Chen,et al.  Peptidic Monodisperse PEG "combs" with Fine-Tunable LCST and Multiple Imaging Modalities. , 2019, Biomacromolecules.

[8]  D. Jirák,et al.  Fluorine polymer probes for magnetic resonance imaging: quo vadis? , 2018, Magnetic Resonance Materials in Physics, Biology and Medicine.

[9]  Jennifer E. Laaser,et al.  19F Magnetic Resonance Imaging of Injectable Polymeric Implants with Multiresponsive Behavior , 2018, Chemistry of Materials.

[10]  Robin H. A. Ras,et al.  A Short-Chain Multibranched Perfluoroalkyl Thiol for More Sustainable Hydrophobic Coatings , 2018, ACS Sustainable Chemistry & Engineering.

[11]  M. McMahon,et al.  Potential detection of cancer with fluorinated silicon nanoparticles in 19F MR and fluorescence imaging. , 2018, Journal of materials chemistry. B.

[12]  Xin Liu,et al.  Mechanisms of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound , 2018, Journal of cellular and molecular medicine.

[13]  Shizhen Chen,et al.  In vivo drug tracking with 19F MRI at therapeutic dose. , 2018, Chemical communications.

[14]  Jin-Chul Kim,et al.  Functionalized Magnetic PLGA Nanospheres for Targeting and Bioimaging of Breast Cancer. , 2018, Journal of nanoscience and nanotechnology.

[15]  L. Jacobs,et al.  Design of triphasic poly(lactic-co-glycolic acid) nanoparticles containing a perfluorocarbon phase for biomedical applications , 2018 .

[16]  C. Michelet,et al.  Efficient Encapsulation of Fluorinated Drugs in the Confined Space of Water-Dispersible Fluorous Supraparticles. , 2017, Angewandte Chemie.

[17]  C. Solans,et al.  Design of parenteral MNP-loaded PLGA nanoparticles by a low-energy emulsification approach as theragnostic platforms for intravenous or intratumoral administration. , 2017, Colloids and surfaces. B, Biointerfaces.

[18]  M. M. Rizvi,et al.  Design and development of a biocompatible montmorillonite PLGA nanocomposites to evaluate in vitro oral delivery of insulin , 2017 .

[19]  M. Saeb,et al.  Modeling and closed-loop control of particle size and initial burst of PLGA biodegradable nanoparticles for targeted drug delivery , 2017 .

[20]  G. Cowin,et al.  Switchable 19F MRI polymer theranostics: towards in situ quantifiable drug release , 2017 .

[21]  D. Saylor,et al.  Polymer degradation and drug delivery in PLGA-based drug-polymer applications: A review of experiments and theories. , 2017, Journal of biomedical materials research. Part B, Applied biomaterials.

[22]  P. Král,et al.  PFPE-Based Polymeric 19F MRI Agents: A New Class of Contrast Agents with Outstanding Sensitivity , 2017 .

[23]  M. Rastaldi,et al.  Ultrasmall polymeric nanocarriers for drug delivery to podocytes in kidney glomerulus , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[24]  P. Ajayan,et al.  Highly versatile SPION encapsulated PLGA nanoparticles as photothermal ablators of cancer cells and as multimodal imaging agents. , 2017, Biomaterials science.

[25]  A. Edefonti,et al.  Polymer Nanoparticle Engineering for Podocyte Repair: From in Vitro Models to New Nanotherapeutics in Kidney Diseases , 2017, ACS omega.

[26]  R. Gobetto,et al.  Superfluorinated and NIR-luminescent gold nanoclusters. , 2017, Chemical communications.

[27]  T. Meade,et al.  (19)F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape. , 2016, ACS nano.

[28]  Gang Bao,et al.  The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. , 2016, Nanomedicine.

[29]  P. Prasad,et al.  Nanochemistry and Nanomedicine for Nanoparticle-based Diagnostics and Therapy. , 2016, Chemical reviews.

[30]  Wei Zhu,et al.  Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II-III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas. , 2016, Chemical reviews.

[31]  Jochen Keupp,et al.  Recent Advances in 19Fluorine Magnetic Resonance Imaging with Perfluorocarbon Emulsions , 2015, Engineering.

[32]  J. Hohlbein,et al.  Complex Coacervate Core Micelles with Spectroscopic Labels for Diffusometric Probing of Biopolymer Networks. , 2015, Langmuir : the ACS journal of surfaces and colloids.

[33]  S. Laurent,et al.  Functionalization of the PEG Corona of Nanoparticles by Clip Photochemistry in Water: Application to the Grafting of RGD Ligands on PEGylated USPIO Imaging Agent. , 2015, Bioconjugate chemistry.

[34]  Arend Heerschap,et al.  Cell tracking using 19F magnetic resonance imaging: Technical aspects and challenges towards clinical applications , 2015, European Radiology.

[35]  G. Cavallo,et al.  Magnetic Resonance Imaging ( MRI ) : From Design of Materials to Clinical Applications , 2014 .

[36]  A. Schwartz-Duval,et al.  Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography. , 2014, Nanoscale.

[37]  Giuseppe Baselli,et al.  A superfluorinated molecular probe for highly sensitive in vivo(19)F-MRI. , 2014, Journal of the American Chemical Society.

[38]  Hong Liu,et al.  Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011). , 2014, Chemical reviews.

[39]  Idriss Blakey,et al.  Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical detection for tunable, targeted, multimodal imaging in vivo. , 2014, Journal of the American Chemical Society.

[40]  Francesco Stellacci,et al.  Gold nanoparticles protected by fluorinated ligands for 19F MRI. , 2013, Chemical communications.

[41]  Mathias Hoehn,et al.  Labeling cells for in vivo tracking using (19)F MRI. , 2012, Biomaterials.

[42]  R. J. Alves,et al.  Synthesis and Characterization of Poly(D,L-Lactide-co-Glycolide) Copolymer , 2012 .

[43]  R. Haag,et al.  Supramolecular behavior of fluorous polyglycerol dendrons and polyglycerol dendrimers with perfluorinated shells in water , 2012 .

[44]  P. Metrangolo,et al.  The fluorous effect in biomolecular applications. , 2012, Chemical Society reviews.

[45]  Arend Heerschap,et al.  (19)F MRI for quantitative in vivo cell tracking. , 2010, Trends in biotechnology.

[46]  A. Elaissari,et al.  Nanotechnology olymer-based nanocapsules for drug delivery , 2009 .

[47]  Cunxian Song,et al.  Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits , 2009, International journal of nanomedicine.

[48]  E. Ahrens,et al.  Fluorine-containing nanoemulsions for MRI cell tracking. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[49]  Antonello A Barresi,et al.  Strategies to control the particle size distribution of poly-epsilon-caprolactone nanoparticles for pharmaceutical applications. , 2008, Journal of colloid and interface science.

[50]  E. Schapoval,et al.  HPLC with Diode-Array Detection for Determination of Leflunomide in Tablets , 2006 .

[51]  Eric T Ahrens,et al.  In vivo imaging platform for tracking immunotherapeutic cells , 2005, Nature Biotechnology.

[52]  Tae Gwan Park,et al.  Folate receptor targeted biodegradable polymeric doxorubicin micelles. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[53]  Ilia Fishbein,et al.  Lipophilic drug loaded nanospheres prepared by nanoprecipitation: effect of formulation variables on size, drug recovery and release kinetics. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[54]  Gavin I. Welsh,et al.  The podocyte cytoskeleton—key to a functioning glomerulus in health and disease , 2012, Nature Reviews Nephrology.

[55]  I. C. Mcneill,et al.  Polymer Chemistry , 1961, Nature.