Specific Endothelial Cells Govern Nanoparticle Entry into Solid Tumors

Kingston, Benjamin R.; Lin, Zachary P.; Ouyang, Ben; MacMillan, Presley; Ngai, Jessica; Syed, Abdullah Muhammad; Sindhwani, Shrey; Chan, Warren C. W.

doi:10.1021/acsnano.1c04510

Cited by 74 publications

(74 citation statements)

References 47 publications

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“…Preferential accumulation of LP-CuET inside tumor tissue due to the EPR effect has been previously shown with various nanoparticle formulations [ 52 , 53 , 54 ]. It is also possible in this case that active transport of the nanoparticles into the tumor is mediated by specialized endothelial cells that could be responsible for the observed large accumulation [ 55 ]. Future studies would need to confirm the presence of these cells in multiple tumor types, including YUMM 1.7, and whether they are involved in nanoparticle transport and retention.…”

Section: Discussionmentioning

confidence: 99%

One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy

et al. 2022

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The metal complex copper diethyldithiocarbamate (CuET) induces cancer cell death by inhibiting protein degradation and induces proteotoxic stress, making CuET a promising cancer therapeutic. However, no clinical formulation of CuET exists to date as the drug is insoluble in water and exhibits poor bioavailability. To develop a scalable formulation, nanoliposomal (LP) CuET was synthesized using ethanol injection as a facile one-step method that is suitable for large-scale manufacturing. The nanoparticles are monodispersed, colloidally stable, and approximately 100 nm in diameter with an encapsulation efficiency of over 80%. LP-CuET demonstrates excellent stability in plasma, minimal size change, and little drug release after six-month storage at various temperatures. Additionally, melanoma cell lines exhibit significant sensitivity to LP-CuET and cellular uptake occurs predominantly through endocytosis in YUMM 1.7 cancer cells. Intracellular drug delivery is mediated by vesicle acidification with more nanoparticles being internalized by melanoma cells compared with RAW 264.7 macrophages. Additionally, the nanoparticles preferentially accumulate in YUMM 1.7 tumors where they induce cancer cell death in vivo. The development and characterization of a stable and scalable CuET formulation illustrated in this study fulfils the requirements needed for a potent clinical grade formulation.

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Section: Discussionmentioning

confidence: 99%

One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy

et al. 2022

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“…For materials to be delivered accurately and efficiently, several obstacles need to be overcome; the barriers are partly related to the means of administration, but there are some other common obstacles, including high interstitial pressure impeding the entry of particles into tissues; 88,89 elimination by the MPS or RES, in which endocytosis of materials may be categorized into phagocytosis, macropinocytosis, clathrinmediated endocytosis, caveolae-dependent endocytosis, and independent endocytosis; [90][91][92] lysosome degradation; 93 and the presence of nucleases in the case of DNA or RNA vaccines.…”

Section: Effects Of Physical Properties Of Delivery Systems On Their ...mentioning

confidence: 99%

Engineering optimal vaccination strategies: effects of physical properties of the delivery system on functions

2022

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“…13 We have started to apply these approaches to understand the distribution of inorganic nanoparticles in tumors based on key features that can only be visualized in 3D, such as the blood vessel structure. 14 However, we were unable to visualize organic nanoparticles, namely, liposomes and polymer nanoparticles.…”

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confidence: 90%

Liposome Imaging in Optically Cleared Tissues

et al. 2020

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Three-dimensional (3D) optical microscopy can be used to understand and improve the delivery of nanomedicine. However, this approach cannot be performed for analyzing liposomes in tissues because the processing step to make tissues transparent for imaging typically removes the lipids. Here, we developed a tag, termed REMNANT, that enables 3D imaging of organic materials in biological tissues. We demonstrated the utility of this tag for the 3D mapping of liposomes in intact tissues. We also showed that the tag is able to monitor the release of entrapped therapeutic agents. We found that liposomes release their cargo >100-fold faster in tissues in vivo than in conventional in vitro assays. This allowed us to design a liposomal formulation with enhanced ability to kill tumor associated macrophages. Our development opens up new opportunities for studying the chemical properties and pharmacodynamics of administered organic materials in an intact biological environment. This approach provides insight into the in vivo behavior of degradable materials, where the newly discovered information can guide the engineering of the next generation of imaging and therapeutic agents.

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Specific Endothelial Cells Govern Nanoparticle Entry into Solid Tumors

Cited by 74 publications

References 47 publications

One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy

One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy

Engineering optimal vaccination strategies: effects of physical properties of the delivery system on functions

Liposome Imaging in Optically Cleared Tissues

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