Study of Biodistribution of Methotrexate-Loaded Bovine Serum Albumin Nanospheres in Mice

Santhi, K; Dhanaraj, S. A.; Koshy, M K; Ponnusankar, Sivasankaran; Suresh, B.

doi:10.1081/ddc-100102311

Cited by 32 publications

(12 citation statements)

References 5 publications

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“…The use of natural carriers can avoid reticuloendothelial system uptake. Previous studies on biodistribution of some nanoparticles revealed that the nanoparticles protected by serum albumin (human serum albumin or BSA) exhibited high retention in liver, lung, and spleen . In this study, the BSA‐protected AuNC also showed relatively high retention in these organs besides in the tumor region.…”

Section: Resultssupporting

confidence: 51%

A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging, EGFR Inhibitor Delivery, and Photothermal Therapy

Zhan

Huang

Lin

et al. 2019

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Gold nanocages (AuNCs) and gold nanoclusters (AuClusters) are two classes of advantageous nanostructures with special optical properties, and many other attractive properties. Integrating them into one nanosystem may achieve greater and smarter performance. Herein, a hybrid gold nanostructure for fluorescent and optoacoustic tomography imaging, controlled release of drugs, and photothermal therapy (PTT) is demonstrated. For this nanodrug (EA–AB), an epidermal growth factor receptor (EGFR) inhibitor erlotinib (EB) is loaded into AuNCs, which are then capped and functionalized by biocompatible AuCluster@BSA (BSA = bovine serum albumin) conjugates via electrostatic interaction. Upon cell internalization, the lysosomal proteases and low pH cause the release of EB from EA–AB, and also induce fluorescence restoration of the AuCluster for imaging. Irradiation with near‐infrared light further promotes the drug release and affords a PTT effect as well. The AuNC‐based nanodrug is optoacoustically active, and its biodistribution and metabolic process have been successfully monitored by whole‐body and 3D multispectral optoacoustic tomography imaging. Owing to the combined actions of PTT and EGFR pathway blockage, EA–AB exhibits marked tumor inhibition efficacy in vivo.

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Section: Resultssupporting

confidence: 51%

A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging, EGFR Inhibitor Delivery, and Photothermal Therapy

Zhan

Huang

Lin

et al. 2019

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“…Smaller particles, including nanoparticles, however, can be accumulated in the lung by agglomeration due to breakdown of repulsive forces between the particles. Several studies have demonstrated accumulation of nanoparticles in the lung [15][16][17][18].…”

Section: Passive Targetingmentioning

confidence: 99%

Factors that Control the Circulation Time of Nanoparticles in Blood: Challenges, Solutions and Future Prospects

Yoo

Chambers²,

Mitragotri³

2010

CPD

466

292

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Numerous types of nanoparticles are being designed for systemic and targeted drug delivery. However, keeping nanoparticles in blood for sufficiently long times so as to allow them to reach their therapeutic target is a major challenge. Upon administration into blood, nanoparticles are quickly opsonized and cleared by the macrophages, thereby limiting their circulation times. Surface-modification of nanoparticles by PEG was developed as the first strategy to prolong nanoparticles circulation. While PEGylation has helped prolong particle circulation, it has several limitations including transient nature of the effect and compromised particle-target interactions. Accordingly, several other approaches have been developed to prolong nanoparticle circulation in blood. These include modification with CD47, modulation of mechanical properties, engineering particle morphology and hitchhiking on red blood cells. In this review, we discuss the factors that affect nanoparticles circulation time and discuss recent progress in development of strategies to prolong circulation time.

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“…After standard solvents used for intravenous formulations failed to keep CCF642 in solution, we explored albumin, an abundant plasma protein with hydrophobic and hydrophilic surfaces. Albumin is FDAapproved as carrier for paclitaxel in Abraxane and bovine as well as human albumin has been used in mice effectively for drug delivery (34,35). Albumin-dissolved CCF642 could be given intravenously without injection reactions in mice, but for ease of administration, we chose the intraperitoneal route and saw promising efficacy without obvious toxicity.…”

Section: Discussionmentioning

confidence: 99%

Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma

et al. 2016

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Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell-based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrowsparing compound, exhibited a submicromolar IC 50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in activesite CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma.

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Study of Biodistribution of Methotrexate-Loaded Bovine Serum Albumin Nanospheres in Mice

Cited by 32 publications

References 5 publications

A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging, EGFR Inhibitor Delivery, and Photothermal Therapy

A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging, EGFR Inhibitor Delivery, and Photothermal Therapy

Factors that Control the Circulation Time of Nanoparticles in Blood: Challenges, Solutions and Future Prospects

Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma

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