Bioinspired Nanoparticles Engineered for Enhanced Delivery to the Bone

Abstract

Targeting therapeutic agents to specific organs in the body remains a challenge despite advances in the science of systemic drug delivery. We have engineered a programmable-bioinspired nanoparticle (P-BiNP) delivery system to simultaneously target the bone and increase uptake in homotypic tumor cells by coating polymeric nanoparticles with programmed cancer cell membranes. This approach is unique in that we have incorporated relevant clinical bioinformatics data to guide the design and enhancement of biological processes that these nanoparticles are engineered to mimic. To achieve this, an analysis of RNA expression from metastatic prostate cancer patients identified ITGB3 (a subunit of integrin α V β 3 ) as overexpressed in patients with bone metastasis. Cancer cells were stimulated to increase this integrin expression on the cell surface, and these membranes were subsequently used to coat cargo carrying polymeric nanoparticles. Physicochemical optimization and characterization of the P-BiNPs showed desirable qualities regarding size, ζ potential, and stability. In vitro testing confirmed enhanced homotypic binding and uptake in cancer cells. P-BiNPs also demonstrated improved bone localization in vivo with a murine model. This novel approach of identifying clinically relevant targets for dual homotypic and bone targeting has potential as a strategy for treatment and imaging modalities in diseases that affect the bone as well as broader implications for delivering nanoparticles to other organs of interest.

Bio-Inspired Nanomaterials for Micro/Nanodevices: A New Era in Biomedical Applications

“…According to studies, compared to uncoated NPs and red blood cell membrane-coated NPs (RBCM-NPs), CCM-NPs have much higher cellular absorption and a strong affinity for source cancer cells [ 283 ]. CCM-NPs can achieve self-recognition, internalization by the source cancer cell lines, and highly selective targeting to the homologous tumor in vivo by adjusting the source of the cell membrane coating [ 284 ]. In tumor imaging, CCM-NPs have been widely employed and frequently functionalized with extra features [ 285 , 286 ].…”

Design principles of bioinspired interfaces for biomedical applications in therapeutics and imaging

“…From the previous example, personalization of cancer treatment can be advantageous as drug delivery to the site of cancer metastasis was significantly enhanced. The feasibility of this concept was further proved by using NPs with a programmed CCM that could target the bone specifically and enhance homotypic tumor uptake (Gdowski et al, 2019).…”

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

“…It can activate matrix metalloproteinase 2 (MMP-2) and accelerate tumor cells secreting cell adherence molecule which contributes to tumor metastasis and neoplastic neovascular formation. ITGβ3 (a subunit of integrin αVβ3) is over-expressed in bone metastatic cancer cells compared to cancer cells from other metastatic organs such as liver, lymph nodes (Ross et al., 2017 ; Gdowski et al., 2019 ). ITGβ3 is a critical factor that contributes to the ability of cancer cells to specifically home and bind to endothelial cells in bone (Kwakwa & Sterling, 2017 ).…”

“…ITGβ3 is a critical factor that contributes to the ability of cancer cells to specifically home and bind to endothelial cells in bone (Kwakwa & Sterling, 2017 ). This targeting bone function of integrin was exploited to engineer a programmable-bioinspired NPs (P-BiNP) to target bone and increase uptake in homotypic tumor cells (Gdowski et al., 2019 ). Researchers employed chemokine factor motif chemokine ligand 12 (CXCL12) to stimulate cancer cells to express more integrin, and purified cancer cell membranes to carry PLGA NPs.…”

“…Researchers employed chemokine factor motif chemokine ligand 12 (CXCL12) to stimulate cancer cells to express more integrin, and purified cancer cell membranes to carry PLGA NPs. In vivo bone homing experiment, P-BiNP had an increased affinity to the bone and decreased affinity to other organs compared to the BiNPs (Gdowski et al., 2019 ). On the other hand, integrin αVβ3 can be a target and recognized by tripeptide Arg − Gly − Asp (RGD) and quinolone nonpeptide specifically (Wang, Cai, et al., 2018 ).…”