Treatment of cancer micrometastasis using a multicomponent chain-like nanoparticle

Abstract

While potent cytotoxic agents are available to oncologists, the clinical utility of these agents is limited due to their non-specific distribution in the body and toxicity to normal tissues leading to use of suboptimal doses for eradication of metastatic disease. Furthermore, treatment of micrometastases is impeded by several biobarriers, including their small size and high dispersion to organs, making them nearly inaccessible to drugs. To circumvent these limitations in treating metastatic disease, we developed a multicomponent, flexible chain-like nanoparticle (termed nanochain) that possesses a unique ability to gain access to and be deposited at micrometastatic sites. Moreover, coupling nanochain particles to radiofrequency (RF)-triggered cargo delivery facilitated widespread delivery of drug into hard-to-reach cancer cells. Collectively, these features synergistically facilitate effective treatment and ultimately eradication of micrometastatic disease using a low dose of a cytotoxic drug.

Gadolinium‐Doped Iron Oxide Nanoprobe as Multifunctional Bioimaging Agent and Drug Delivery System

“…[1][2][3] However, these therapies still have limitations such as (1) inability to bypass biological barriers, (2) nontargeted delivery and passive distribution of drugs, (3) ineffectiveness against metastatic disease, and (4) lack of an effective modality for treatment monitoring. [4][5][6][7] Over the past 20 years, the development of nanotechnology has provided some potential methods to overcome these challenges. An example of such a methodology utilizes a single nano medicine for the dual purpose of targeted drug delivery and in vivo drug monitoring.…”

Smart nanoparticles for drug delivery: Boundaries and opportunities

“…Currently, most chemotherapy focuses on primary tumors, even though metastatic disease is responsible for the majority of cancer deaths. Recently, a new design of a multicomponent nanochain formulation was designed to take the microenvironment of micrometastasis into consideration for cancer treatment [38]. Three iron oxide nanospheres are chemically linked to one doxorubicin-loaded liposome to make a linear, chain-like assembly.…”

“…Typically, when a patient is diagnosed with cancer, the first-line treatment includes surgery to remove the primary tumor, followed by chemotherapy to eradicate any residual disease, including micrometastases at distant organs. Nanoparticle-based drug delivery may be useful in well-vascularized tumors that are several millimeters in diameter, but it is ineffective against micrometastases, which presents small clusters of malignant cells dispersed within variable tissue types [38]. …”

Targeted nanotechnology for cancer imaging

“…For example, a chain-shaped iron oxide nanoparticle targeted to the α v β 3 integrin bound with 2.9 fold higher avidity than a spherical counterpart targeted to the same receptor in a microfluidic channel [56]. In vivo , vascular targeting of the iron oxide nanochain to the α v β 3 integrin resulted in a tenfold higher deposition at the site of a metastasis than its spherical counterparts [92]. The flexibility of the nanochain is also thought to improve its ability to bind to the vascular bed.…”

“…The size, shape, and flexibility of the nanochains significantly increase the lateral drift and margination of the particles towards the blood vessel walls in microcirculation ( i.e., continuous scavenging of vascular walls) and targeting avidity of nanoparticles ( i.e., latching on vascular target) due to geometrically enhanced multivalent attachment on the vascular target. In a mouse model of breast cancer metastasis, a remarkable 6% of the nanochains injected in a mouse model congregated within a micrometastatic site of less than 1 mm in size [92]. In comparison, less than 1% of injected dose of its targeted spherical counterpart reached the micrometastasis.…”