Prostate-specific membrane antigen–directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells

Abstract

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigenpositive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

Characteristics of temperature changes in photothermal therapy induced by combined application of indocyanine green and laser

“…The aforementioned phenomenon remains a challenge to avoid. Secondly, tissue heterogeneity is another factor that influences temperature elevation (34). Different types of tumor tissues have different optical properties, which generate different temperatures in different tumor tissues or in different parts of a tumor, with the same laser power.…”

Light-Induced Therapies for Prostate Cancer Treatment

“…Over the past decade, many different types of NIR-absorbing agents have been developed, such as metal-based and other inorganic nanomaterials and organic nanomaterials, thus providing a large spectrum of opportunities for this technique to access clinical practice (Phan et al, 2018). In this section, a selection of papers was reported on the PTT and or PTT-combined treatment of PC (Lee et al, 2017; Thapa et al, 2018).…”

“…Vascular-targeted PDT is a PDT regimen that preferentially targets abnormal blood vessels through selective delivery of PS molecules to the vasculature (Kraus et al, 2017). Conversely to other therapeutic approaches, such as surgery and chemotherapy, VPDT is less invasive, does not suffer of life-threating drawbacks and, being a physical therapy, is lethal to tumor cells irrespective of their genetic background, as long as they are present within the targeted area (Lee et al, 2017).…”

Investigation of the Association of FOLH1 rs61886494 and DISC1 rs12133766 loci in Iranian Schizophrenia Patients

“…Expression of this protein in the brain may be involved in a number of pathological conditions associated with stimulation of glutamate toxicity. In the prostate, protein is regulated in cancer cells and is used as an indicator of the diagnosis and prognosis of prostate cancer [13][14][15]. FOLH1 is also expressed in the brain by disrupting NAAG (n-acetyl-aspartyl glutamate) into NAA and glutamate in disorders of the nervous system, such as multiple sclerosis, sclerosis, Alzheimer's disease and schizophrenia due to impairs in FOLH1 at various levels [16,17].…”