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Drug Delivery

Drug Delivery - Poster Session D

Poster X17 - Collagen matrix-specific peptide decorated nanocarriers for tumor microenvironment targeted drug delivery

Friday, October 25, 2024
3:30 PM – 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Cancer poses a global health challenge due to its heterogeneity and resistance to therapy. Targeting the tumor microenvironment (TME), including the extracellular matrix (ECM), is a promising approach. The ECM, particularly denatured collagen IV altered by matrix metalloproteinase-2 (MMP-2), supports tumor invasion. Nanotechnology-based drug delivery systems, like liposomal platforms, can encapsulate and selectively deliver therapeutic agents. Our study focuses on developing a novel liposomal formulation for Paclitaxel, using MCF-7 as a breast cancer model and modifying liposome surfaces with a denatured collagen binding protein (DCBP). This approach aims to enhance specificity and efficacy in targeting altered ECM structures, advancing personalized cancer treatment strategies.

Materials and

Methods:  Empty and PTX-loaded liposomes were prepared using solvent evaporation. Collagen-binding peptide-bound PTX-liposomes were prepared by conjugation via click chemistry. The liposome's size, stability, zeta potential, and polydispersity index were characterized using dynamic light scattering (DLS). The encapsulation efficiency of PTX was evaluated using a UV-Vis spectrophotometer. Cytotoxicity, colony formation, and cell migration assays were performed to assess therapeutic efficiency. Co-culture spheroids were developed using endothelial cells, fibroblasts, and MCF-7 cells to investigate 3D targeting. Live/dead assays, brightfield imaging, and immunofluorescence imaging were conducted to evaluate morphological changes in the spheroids at various time points post-treatment.

Results, Conclusions, and Discussions: The study investigated the characteristics and effects of various liposomes on MCF-7 cells. The sizes of Nile red-loaded, PTX-loaded, and CBP-bound Nile red liposomes were found to be 78.7 ± 64.5 nm, 66.5 ± 14.1 nm, and 156 ± 37.1 nm, respectively, with zeta potentials of -6.96 ± 0.5 mV, -5.52 ± 0.378 mV, and -3.94 ± 2.28 mV. The encapsulation efficiency of PTX -Liposomes ranged from 42.25% to 63.5%. In MCF-7 cells, PTX-loaded liposomes at concentrations of 20 nM, 40 nM, 1 µM, and 10 µM significantly decreased cell viability after 48 hours, with 1 nM showing approximately 60% cell death. The Scratch Assay demonstrated that 40 and 10 µM PTX-loaded liposomes effectively reduced MCF-7 cell migration over 72 hours. Furthermore, these liposomes significantly inhibited colony formation, highlighting their enhanced therapeutic potential in cancer treatment. The targeting efficiency of CBP-Liposomes was confirmed using co-culture spheroids with a denatured collagen matrix. Spheroids treated with varying concentrations of PTX-loaded liposomes revealed notable disintegration in spheroid morphology by day 5. A stable tumor microenvironment targeted liposomal formulation was developed to improve the bioavailability and therapeutic efficiency of cancer treatment.

Acknowledgements (Optional):  Blazer Foundation, MBT Program at UIC.