Radiolabeling of Poly(lactic-<i>co</i>-glycolic acid) (PLGA) Nanoparticles with Biotinylated F-18 Prosthetic Groups and Imaging of Their Delivery to the Brain with Positron Emission Tomography

Sirianni, Rachael W.; Zheng, Mingjie; Patel, Toral; Shafbauer, Thomas; Zhou, Jiangbing; Saltzman, W. Mark; Carson, Richard E.; Huang, Yiyun

doi:10.1021/bc500315j

Cited by 48 publications

(46 citation statements)

References 27 publications

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“…Alternatively, fluorescent or radioactive labeling strategies can permit direct tracking of the nanoparticle itself [45, 46]. Evaluation of new nanoparticle designs would ideally incorporate both measurements, since the techniques provide complementary information.…”

Section: Discussionmentioning

confidence: 99%

A critical evaluation of drug delivery from ligand modified nanoparticles: Confounding small molecule distribution and efficacy in the central nervous system

Cook

Householder

Chung

et al. 2015

Journal of Controlled Release

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In this work, we sought to test how surface modification of poly(lactic-co-glycolic acid) (PLGA) nanoparticles with peptide ligand alters the brain specific delivery of encapsulated molecules. For biodistribution studies, nanoparticles modified with rabies virus glycoprotein (RVG29) were loaded with small molecule drug surrogates and administered to healthy mice by lateral tail vein injection. Mice were perfused two hours after injection and major anatomical regions of the CNS were dissected (striatum, midbrain, cerebellum, hippocampus, cortex, olfactory bulb, brainstem, and cervical, thoracic, lumbar and sacral spinal cord). For functional studies, surface modified nanoparticles were loaded with the chemotherapeutic camptothecin (CPT) and administered to mice bearing intracranial GL261-Luc2 gliomas. Outcome measures included tumor growth, as measured by bioluminescent imaging, and median survival time. We observed that small molecule delivery from PLGA nanoparticles varied by as much as 150% for different tissue regions within the CNS. These differences were directly correlated to regional differences in cerebral blood volume. Although the presence of RVG29 enhanced apparent brain delivery for multiple small molecule payloads, we observed minimal evidence for targeting to muscle or spinal cord, which are the known sites for rabies virus entry into the CNS, and enhancements in brain delivery were not prolonged due to an apparent aqueous instability of the RVG29 ligand. Furthermore, we have identified concerning differences in apparent delivery kinetics as measured by different payloads: nanoparticle encapsulated DiR was observed to accumulate in the brain, whereas encapsulated Nile red was rapidly cleared. Although systemically administered CPT loaded nanoparticles slowed the growth of orthotopic brain tumors to prolong survival, the presence of RVG29 did not enhance therapeutic efficacy compared to control nanoparticles. These data are consistent with a model of delivery of hydrophobic small molecules to the brain that does not rely on internalization of polymer nanoparticles in target tissue. We discuss an important risk for discordance between biodistribution, as typically measured by drug surrogate, and therapeutic outcome, as determined by clinically relevant measurement of drug function in a disease model. These results pose critical considerations for the methods used to design and evaluate targeted drug delivery systems in vivo.

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Section: Discussionmentioning

confidence: 99%

A critical evaluation of drug delivery from ligand modified nanoparticles: Confounding small molecule distribution and efficacy in the central nervous system

Cook

Householder

Chung

et al. 2015

Journal of Controlled Release

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“…Pep22, a polypeptide with specific affinity for LDLR, effectively binds to LDLR overexpressed in glioma and BBB, thereby increasing glioma targeting of loaded drugs …”

Section: Discussionmentioning

confidence: 99%

Combination Glioma Therapy Mediated by a Dual‐Targeted Delivery System Constructed Using OMCN–PEG–Pep22/DOX

Qian

Wang

et al. 2018

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were obtained with an Olympus IX71 microscope. At the same time, the transendothelial electrical resistance (TEER) value (>300 Ω cm −2 ) was monitored to validate the reliability of these models. No obvious reduction in the TEER values was observed during the whole experiment, indicating that the transport of drug system did not compromise the BBB barrier properties. All animals were maintained in a pathogen-free environment and fed ad libitum. The procedures for the care and use of animals were approved by the Ethics Committee of Nantong University and all institutional and governmental regulations concerning the ethical use of animals followed.

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“…Several studies detailing the development of SPECT and PET contrast agents based on polyesters have been disclosed . This section will focus on two reports using the conventional PLGA polymer.…”

Section: Polyesters With Imaging Contrast Propertiesmentioning

confidence: 99%

“…This section will focus on two reports using the conventional PLGA polymer. Sirianni et al described the radiolabeling of biotinylated F‐18 prosthetic groups with PLGA polymer NPs with the intent for use in monitoring their delivery to the brain by PET imaging . The strong and irreversible noncovalent interaction of biotin‐avidin substrates allow for [ 18 F]4‐fluorobenzylamine to react with NHS‐PEG4‐biotin.…”

Section: Polyesters With Imaging Contrast Propertiesmentioning

confidence: 99%

Recent Advances in Polyesters for Biomedical Imaging

Attia

Brummel

Lex

et al. 2018

Adv Healthcare Materials

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Several synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. Polymeric biomaterials and metals are commonly used imaging agents and can assist in the monitoring of therapy response, migration, degradation, changes in morphology, defects, and image-guided surgery. In comparison to metals, most bio and synthetic polymers lack inherent imaging properties. Polymeric biomaterials, specifically polyesters, have gained a considerable amount of attention due to their unique properties including biocompatibility, biodegradation, facile synthesis, and modification capability. Polyester implants and nanomaterials are available on the market or are in clinical trials for many applications including: dental implants, cranio-maxilofacial implants, soft tissue sutures and staples, abdominal wall repair, tendon and ligament reconstruction, fracture fixation devices, and coronary drug eluting stents. This review aims to provide a summary of the recent developments of polyesters with bioimaging contrast properties. The three main approaches to prepare bioimaging polyesters (coating, encapsulation, and functionalization) are discussed in depth. Furthermore, commonly used imaging modalities including X-ray computed tomography, magnetic resonance imaging, ultrasound, fluorescence, and radionucleotide polyester contrast agents are highlighted. In each section, examples of impactful bioimaging polyesters in the five major imaging modalities are evaluated.

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Radiolabeling of Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles with Biotinylated F-18 Prosthetic Groups and Imaging of Their Delivery to the Brain with Positron Emission Tomography

Cited by 48 publications

References 27 publications

A critical evaluation of drug delivery from ligand modified nanoparticles: Confounding small molecule distribution and efficacy in the central nervous system

A critical evaluation of drug delivery from ligand modified nanoparticles: Confounding small molecule distribution and efficacy in the central nervous system

Combination Glioma Therapy Mediated by a Dual‐Targeted Delivery System Constructed Using OMCN–PEG–Pep22/DOX

Recent Advances in Polyesters for Biomedical Imaging

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