A Multimodal Theranostic System Prepared from High-Density Lipoprotein Carrier of Doxorubicin and 177Lu

2021 ◽  
Vol 17 (11) ◽  
pp. 2125-2141
Author(s):  
Hilda Angeline Quintos-Meneses ◽  
Liliana Aranda-Lara ◽  
Enrique Morales-Ávila ◽  
Blanca Ocampo-García ◽  
Irazú Contreras ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Laser Light ◽  
Chemotherapeutic Agent ◽  
Human Fibroblasts ◽  
Density Lipoprotein ◽  
Nuclear Imaging ◽  
High Density ◽  
B1 Receptors ◽  
B1 Receptor

Recently, it was demonstrated that doxorubicin (Dox.HCl), a chemotherapeutic agent, could be photoactivated by Cerenkov radiation (CR). The objective of the present work was to develop a multimodal chemotherapy-radiotherapy-photodynamic therapeutic system based on reconstituted high-density lipoprotein (rHDL) loaded with Dox.HCl and 177Lu-DOTA. 177Lu acts as a therapeutic radionuclide and CR source. The system can be visualized by nuclear imaging. Fluorescence microscopy showed that rHDL-Dox specifically recognized cancer cells (T47D) that are positive for SR-B1 receptors. Encapsulated Dox.HCl was released into the cells and produced reactive oxygen species when irradiated with a 450-nm laser (photodynamic effect). The same effect occurred when Dox.HCl was irradiated by 177Lu CR. Through in vitro experiments, it was confirmed that the addition of 177Lu-DOTA to the rHDL-Dox nanosystem did not affect the specific recognition of SR-B1 receptors expressed in cells, or the cellular internalization of 177Lu-DOTA. The toxicity induced by the rHDL-Dox/177Lu nanosystem in cell lines with high (T47D and PC3), poor (H9C2) and almost-zero (human fibroblasts (FB)) expression of SR-B1 was evaluated in vitro and confirmed the synergy of the combined chemotherapy-radiotherapy-photodynamic therapeutic effect; this induced toxicity was proportional to the expression of the SR-B1 receptor on the surface of the cells used. The HDL-Dox/177Lu nanosystem experienced uptake by tumor cells and the liver-both tissues with high expression of SR-B1 receptors-but not by the heart. 177Lu CR offered the possibility of imparting photodynamic therapy where laser light could not reach.

Rapid transformation of [3H]cholesteryl ester m rat high-density lipoprotein: in vivo and in vitro studies

Steroids ◽  
1990 ◽  
Vol 55 (7) ◽  
pp. 308-313
Author(s):  
I.J. Goldberg ◽  
R.S. Rosenfeld ◽  
I. Paul ◽  
L.K. Miller ◽  
M.L. Tiell
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Density Lipoprotein ◽  
High Density ◽  
In Vitro Studies ◽  
Rapid Transformation

scholarly journals Light and electron microscopical observations of the effects of high-density lipoprotein on growth of Plasmodium falciparum in vitro

Parasitology ◽  
2004 ◽  
Vol 128 (6) ◽  
pp. 577-584 ◽  
Author(s):  
H. IMRIE ◽  
D. J. P. FERGUSON ◽  
M. CARTER ◽  
J. DRAIN ◽  
A. SCHIFLETT ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Density Lipoprotein ◽  
Light And Electron Microscopy ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
High Density ◽  
High Concentrations ◽  
Electron Microscopical ◽  
Necessary And Sufficient

Human serum high-density lipoprotein (HDL) is necessary and sufficient for the short-term maintenance of Plasmodium falciparum in in vitro culture. However, at high concentrations it is toxic to the parasite. A heat-labile component is apparently responsible for the stage-specific toxicity to parasites within infected erythrocytes 12–42 h after invasion, i.e. during trophozoite maturation. The effects of HDL on parasite metabolism (as determined by nucleic acid synthesis) are evident at about 30 h after invasion. Parasites treated with HDL show gross abnormalities by light and electron microscopy.

scholarly journals In Vitro Generation of Human High-Density-Lipoprotein-Resistant Trypanosoma brucei brucei

2006 ◽  
Vol 5 (8) ◽  
pp. 1276-1286 ◽  
Author(s):  
Sara D. Faulkner ◽  
Monika W. Oli ◽  
Rudo Kieft ◽  
Laura Cotlin ◽  
Justin Widener ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Trypanosoma Brucei ◽  
Density Lipoprotein ◽  
High Density ◽  
Surface Glycoprotein ◽  
Trypanosoma Brucei Brucei ◽  
African Trypanosomes ◽  
Expression Site ◽  
Human High Density Lipoprotein

ABSTRACT The host range of African trypanosomes is influenced by innate protective molecules in the blood of primates. A subfraction of human high-density lipoprotein (HDL) containing apolipoprotein A-I, apolipoprotein L-I, and haptoglobin-related protein is toxic to Trypanosoma brucei brucei but not the human sleeping sickness parasite Trypanosoma brucei rhodesiense. It is thought that T. b. rhodesiense evolved from a T. b. brucei-like ancestor and expresses a defense protein that ablates the antitrypanosomal activity of human HDL. To directly investigate this possibility, we developed an in vitro selection to generate human HDL-resistant T. b. brucei. Here we show that conversion of T. b. brucei from human HDL sensitive to resistant correlates with changes in the expression of the variant surface glycoprotein (VSG) and abolished uptake of the cytotoxic human HDLs. Complete transcriptome analysis of the HDL-susceptible and -resistant trypanosomes confirmed that VSG switching had occurred but failed to reveal the expression of other genes specifically associated with human HDL resistance, including the serum resistance-associated gene (SRA) of T. b. rhodesiense. In addition, we found that while the original active expression site was still utilized, expression of three expression site-associated genes (ESAG) was altered in the HDL-resistant trypanosomes. These findings demonstrate that resistance to human HDLs can be acquired by T. b. brucei.

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