In vivo stability of protein coatings on poly lactic co glycolic nanoparticles
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In vivo stability of protein coatings on poly lactic co glycolic nanoparticles Jordi Llop,1 Marco Marradi2, Pengfei Jiang 4 , Vanessa Gómez-Vallejo3, Zuriñe Baz,1 María Echeverría2, Changyou Gao4, Sergio E. Moya 2 1
Radiochemistry and Nuclear Imaging Group, CIC biomaGUNE, San Sebastián, Spain.
2
Soft Mater Nanotechnology Laboratory, CIC biomaGUNE, San Sebastián, Spain.
3
Radiochemistry Platform, CIC biomaGUNE, San Sebastián, Spain.
4
MOE Key Laboratory of Macrmolecular Synthesis and Functionalization, Department of
Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
ABSTRACT Submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) are dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. PLGA core is labelled by encapsulation of 111In-doped iron oxide NPs inside PLGA-NPs during NP preparation, while the BSA coating is labelled by electrophilic substitution using 125I. After intravenous administration into rats, energydiscriminant single-photon emission computerised tomography (SPECT) resolved each radioisotope independently. Imaging revealed different fates for the core and coating, with a fraction of the two radionuclides co-localising in the liver and lungs for long periods of time after administration, suggesting that NPs are stable in these organs. The general methodology reported here represents an excellent alternative for visualising the degradation process of multi-labelled NPs in vivo and can be extended to a wide range of engineered NPs. INTRODUCTION The use of Nanomaterials (NMs) in medical applications requires the determination of their biodistribution pattern and biological fate. Knowledge about the capacity of NMs to accumulate is selected organs or tissues can provide meaningful information to predict either therapeutic efficacy or diagnostic capacity [1]. One of the few options to determine the loci of NMs in vivo consists of radiolabelling with a positron or gamma emitter followed by in vivo imaging using Positron Emission Tomography (PET) or Single Photon Emission Computerized Tomography (SPECT). This strategy has been widely reported in the literature [2,3,4,5,6]. However, the incorporation of a single radioisotope fails in the assessment of the stability of NMs in vivo. Precise knowledge about the degradation of NMs is paramount in the assessment of the biological fate of NMs, as such degradation can significantly alter toxicological endpoints or trigger the delivery of therapeutic agents in specific locations within the body.
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Recently the degradation of NPs both in vivo and ex vivo has been followed by multiple radiolabelling [7-9]. Here we demonstrate that incorporation of two radionuclides with not fully overl
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