Synergistic Targeting of Cell Membrane, Cytoplasm, and Nucleus of Cancer Cells Using Rod-Shaped Nanoparticles

Design of carriers for effective delivery and targeting of drugs to cellular and subcellular compartments is an unmet need in medicine. Here, we report pure drug nanoparticles comprising camptothecin (CPT), trastuzumab (TTZ), and doxorubicin (DOX) to enable cell-specific interactions, subcellular accumulation, and growth inhibition of breast cancer cells. CPT is formulated in the form of nanorods which are coated with TTZ. DOX is encapsulated in the TTZ corona around the CPT nanoparticle. Our results show that TTZ/DOX-coated CPT nanorods exhibit cell-specific internalization in BT-474 breast cancer cells, after which TTZ is recycled to the plasma membrane, leaving CPT nanorods in the perinuclear region and delivering DOX into the nucleus of the cells. The effects of CPT-TTZ-DOX nanoparticles on growth inhibition are synergistic (combination index = 0.17 ± 0.03) showing 10–10 000-fold lower inhibitory concentrations (IC₅₀) compared to those of individual drugs. The design of antibody-targeted pure drug nanoparticles offers a promising design strategy to facilitate intracellular delivery and therapeutic efficiency of anticancer drugs

MOESM1 of A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles

Additional file 1: Model Source Code. The compressed folder, S1_File.zip, contains necessary files and instructions to run a simulation. The file named main.cpp contains the C++ source code. The file named README.txt contains necessary instructions to compile the code and execute the simulation. (ZIP 8 kb

MOESM2 of A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles

Additional file 2: Time Adaptive Motion of a Particle. (A) Movie file S1_Video_A.mp4 shows the time-adaptive motion of a single nanoparticle in the interstitial space and near the cell boundaries. Only the motion of the particle center is shown. (B) Movie file S1_Video_B.mp4 shows a more zoomed-in view. Both the particle and the cell are represented by circles. The circles are scaled based on their relative size in the model (particle radius 100 nm and cell radius 10 Îźm). (ZIP 821 kb