Biotin-streptavidin-guided two-step pretargeting approach using PLGA for molecular ultrasound imaging and chemotherapy for ovarian cancer

Abstract

Background Ovarian cancer seriously threatens the lives and health of women, and early diagnosis and treatment are still challenging. Pre-targeting is a promising strategy to improve the treatment efficacy of ovarian cancer and the results of ultrasound imaging. Purpose To explore the effects of a pre-targeting strategy using streptavidin (SA) and paclitaxel (PTX)-loaded phase-shifting poly lactic-co-glycolic acid (PLGA) nanoparticles with perfluoro-n-pentane (PTX-PLGA-SA/PFPs) on the treatment and ultrasound imaging of ovarian cancer. Methods PTX-PLGA/PFPs were prepared with a single emulsion (O/W) solvent evaporation method and SA was attached using carbodiimide. The encapsulation efficiency of PTX and the release characteristics were assessed with high performance liquid chromatography. The phase-change characteristics of the PTX-PLGA-SA/PFPs were investigated. The anti-carcinoembryonic antigen (CEA) antibody (Ab) was covalently attached to PTX-PLGA/PFPs via carbodiimide to create PTX-PLGA-Ab/PFPs. The targeting efficiency of the nanoparticles and the viability of ovarian cancer SKOV3 cells were evaluated in each group using a microscope, flow cytometry, and cell counting kit 8 assays. Results THE PTX-PLGA-SA/PFPs were spheres with a size of 383.0 ± 75.59 nm. The encapsulation efficiency and loading capability of the nanoparticles for PTX were 71.56 ± 6.51% and 6.57 ± 0.61%, respectively. PTX was burst-released up to 70% in 2–3 d. When irradiated at 7.5 W for 3 min, the PTX-PLGA-SA/PFPs visibly enhanced the ultrasonography images (P < 0.05). At temperatures of 45°C and 60°C the nanoparticles phase-shifted into micro-bubbles and the sizes increased. The binding efficiencies of SA and Ab to the PTX-PLGA/PFPs were 97.16 ± 1.20% and 92.74 ± 5.75%, respectively. Pre-targeting resulted in a high binding efficacy and killing effect on SKOV3 cells (P < 0.05). Conclusions The two-step pre-targeting process can significantly enhance the targeting ability of PTX-loaded PLGA nanoparticles for ovarian cancer cells and substantially improve the therapeutic efficacy. This technique provides a new method for ultrasonic imaging and precise chemotherapy for ovarian cancer.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies

“…Upon irradiation at 7.5 W, the PTX-PLGA-streptavidin/PFPs complex enhanced the cancer cell visibility by US imaging. Moreover, with the rise in temperature due to irradiation as well as LIFU resulted in the phase-shifting of PTX-PLGA nanoparticles into MBs, thereby augmenting the efficiency of the killing of SKOV3 cells ( 47 ). This technique thus offers a dual function strategy of US-based imaging and cancer cell killing.…”

“…Carcinoembryonic antigen (CEA), which increases in both colon cancer and OCs (45, 46) is commonly used in gynecological cancer screening. Zhou et al fabricated molecular US imaging and chemotherapy by targeting CEA (47). To this aim, a two-step targeting strategy was employed; i) in the first step, PTX-loaded heat-induced phase-shifting PLGA nanoparticles with perfluoro-n-pentane (PFP) were prepared and ii) in the second step, PTX-PLGA-streptavidin/PFPs and PTX-PLGA-anti-CEA antibody/PFPs were prepared.…”

Pretargeted Alpha Therapy of Disseminated Cancer Combining Click Chemistry and Astatine-211

“…Today, several pretargeting strategies can be used to combine antibodies and radioligands in vivo; some of them utilize a noncovalent interaction such as streptavidinbiotin [9][10][11], and some utilize the hybridization of complementary oligonucleotides [12,13] or the ability of bispecific antibodies [14,15] to bind an antigen and a radiolabeled hapten. Last but not least, there is the biorthogonal inverse electron demand Diels-Alder (IEDDA) click reaction, which utilizes the fast and highly specific reaction that occurs between a diene, such as 1,2,4,5-tetrazine (Tz), and a dienophile, particularly trans-cyclooctene (TCO), which appears to be seven times more reactive than the cis-cyclooctene (CCO) in the IEDDA reaction [15][16][17][18][19].…”

The targeting imaging and treatment capacity of gelsolin-targeted and paclitaxel-loaded PLGA nanoparticles in vitro and in vivo

“…However, the clinical efficacy of PTX is often compromised due to its poor aqueous solubility, low drug utilization rate, and serious adverse effects ( Singh and Dash, 2009 ). Poly(lactic-co-glycolic acid) (PLGA) is a new nanoscale biomaterial and is widely applied to the preparation of contrast agents ( Zhou et al, 2021 ). Due to its favorable stability, biocompatibility, and biodegradability, PLGA is used to prepare nanoparticle shells coupled with active substances, including monoclonal antibodies, ligands, and various specific short peptides, and load drugs on its surface ( Mahapatro and Singh, 2011 ; Wang et al, 2021 ).…”