Cancer targeted drug delivery using active low-density lipoprotein nanoparticles encapsulated pyrimidines heterocyclic anticancer agents as microtubule inhibitors

Abstract

Recently, nanomedicine had the potential to increase the delivery of active compounds to specific cell sites. Nano-LDL particles are recognized as an excellent active nano-platform for cancer-targeted delivery. Loading of therapeutic agents into nano-LDL particles achieved by surface loading, core loading, and apolipoprotein-B100 interaction. Therefore, loading nano-LDL particles’ core with pyrimidine heterocyclic anticancer agents will increase cancer cytotoxic activity targeting tubulin protein. First, by mimicking the native LDL particle's metabolic pathway, and second the agent’s chemical functional groups like the native amino acids cytosine and thymine structures will not be recognized as a foreign entity from the cell’s immune system. Nano-LDL particles will internalize through LDL-receptors endocytosis and transport the anticancer agent into the middle of the cancer cell, reducing its side effects on other healthy cells. Generally, the data revealed that pyrimidine heterocyclic anticancer agents’ size is at the nano level. Agents’ morphological examination showed nanofibers, thin sheets, clusters, and rod-like structures. LDL particles’ size became bigger after loading with pyrimidine heterocyclic anticancer agents and ranged between 121.6 and 1045 nm. Then, particles were tested for their cytotoxicity against breast (MDA468) and prostate (DU145) cancer cell lines as surrogate models with dose-response study 10, 5, 1 µM. The IC 50 values of the agents against DU145 and MDA468 possessed cell growth inhibition even at the 1 µM concentration ranges of 3.88 ± 1.05 µM and 3.39 ± 0.97 µM, respectively. In sum, nano-LDL particles proved their efficiency as active drug delivery vehicles to target tubulin in cancer cells.

Protein-Caged Nanoparticles: A Promising Nanomedicine Against Cancer

“…PNPs nanoparticles not only successfully reduced cervical tumors but also actively help in various tumor inhibition that is provided in Table 2 . 61 62 63 64 65 66 67 68 69 70 71 72 73 …”

Enrichment and delivery of target proteins into the cell cytosolviaOuter Membrane Vesicles

“…6 As the significance of intracellular protein delivery has been well recognized, multiple methods were developed for cellular protein delivery including physical methods, cell-penetrating peptides, polyethyleneimine, supercharged molecules, and nanocarriers in the past decades. [7][8][9][10][11] Most of these transportation systems have remained limitations in different aspects. Physical methods such as electroporation, microinjection, or microinjection, mainly use physical forces to temporally generate pores on the cell membrane to allow proteins to transport into cells, but they often induce damage to cell membranes and have limited throughput.…”

Enrichment and Delivery of Target Proteins into the Cell Cytosol via Outer Membrane Vesicles

“…As the significance of intracellular protein delivery has been well recognized, multiple methods were developed for cellular protein delivery including physical methods, cell-penetrating peptides, polyethyleneimine, supercharged molecules, and nanocarriers in the past decades. − Most of these transportation systems have contained limitations in different aspects. Physical methods such as electroporation, microinjection, or microfluidics mainly use physical forces to temporally generate pores on the cell membrane to allow proteins to transport into cells, but they often induce damage to the cell membranes and have limited throughput .…”