Novel multifunctional triple folic acid, biotin and CD44 targeting pH-sensitive nano-actiniaes for breast cancer combinational therapy

Abstract

In this study, novel multifunctional folic acid, biotin, and CD44 receptors targeted and pH-sensitive “nano-actiniaes” were fabricated with icariin (ICA) and curcumin (Cur) as loaded model drugs for breast cancer therapy. The newly synthesized polymer oligomeric hyaluronic acid-hydrazone bond-folic acid-biotin (Bio-oHA-Hyd-FA) was characterized by 1H NMR spectrogram (proton nuclear magnetic resonance). The obtained drug carrier Bio-oHA-Hyd-FA self-assembled into nanomicelles, named as “nano-actiniaes”, in aqueous media with hydrodynamic diameter of 162.7 ± 5 nm. The size, surface zeta potential, and morphology of the “nano-actiniaes” were observed via TEM. The in vitro release experiment indicated that much more encapsulated icariin (ICA) and curcumin (Cur) were released from the Bio-oHA-Hyd-FA micelles (nano-actiniaes) in the acidic environment. Additionally, the cytotoxicity research demonstrated that the Bio-oHA-Hyd-FA carrier material was completely nontoxic, and the ICA&Cur “nano-actiniaes” had greater cytotoxicity compared with other control groups. In addition, the “nano-actiniaes” were found to significantly inhibit cancer cell invasion by Transwell assay. Moreover, in vivo evaluation of anti-tumor effect illustrated that the ICA and Cur “nano-actiniaes” possessed inhibitory effect on tumors. Consequently, the multi-targeted pH-sensitive “nano-actiniaes” can realize significant tumor targeting and effectively inhibit tumor growth.

Add the Finishing Touch: Molecular Engineering of Conjugated Small Molecule for High‐Performance AIE Luminogen in Multimodal Phototheranostics

“…The approach consists of dual tumortargeting specificity: first, the polymer encapsulated-NPs can passively accumulate in the tumor tissues via the enhanced permeability and retention (EPR) effect; second, biotin (vitamin H or coenzyme R) as an essential micronutrient is mainly taken up by cells through its receptor sodium dependent multivitamin transporter (SMVT), which is overexpressed in a variety of tumors than in normal tissues. [54][55][56][57][58] The two molecules were respectively assembled into NPs by using a nanoprecipitation method in which two copolymers DSPE-mPEG2000 and DSPE-PEG2000-Biotin with a weight ratio of 95%:5% are utilized as the coating matrix (Figure 1). Dynamic light scattering (DLS) measurement reveals that the hydrodynamic diameters of IDT and IDT-TPE NPs are 78 and 81 nm, respectively.…”

Dual Hyaluronic Acid and Folic Acid Targeting pH-Sensitive Multifunctional 2DG@DCA@MgO-Nano-Core–Shell-Radiosensitizer for Breast Cancer Therapy

“…Moreover, the DDM was surface conjugated with HA and FA to target CD44 and FR-α receptors, which are overexpressed in BC cells. Similarity, CD44 and folate receptors have a high affinity for HA and FA, which is usually captured to nourish fast-dividing BC cells [ 18 ]. Therefore, our design innovation was underpinned by a novel biodegradable multi-target nanocarrier that targets the overexpressed CD44 and FR-α receptors in BC cells.…”

Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells

“…Biotin is essential for normal cell growth and serves as co-enzyme for carboxylase enzymes in the synthesis of fatty acids and branched chain amino acids [32,33]. Solid tumor cells require high levels of biotin due to their high metabolic activity [34]. Biotin receptors are overexpressed on the surface of many tumor cells and thus represent a biomarker for targeting tumor cells [35][36][37][38].…”