Development a hyaluronic acid ion-pairing liposomal nanoparticle for enhancing anti-glioma efficacy by modulating glioma microenvironment

<p>Glioma, one of the most common brain tumors, remains a challenge worldwide. Due to the specific biological barriers such as blood–brain barrier (BBB), cancer stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then, these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which showed near-spherical morphology with an average size of 155.8 nm and uniform distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor, which is over-expressed on the surface of tumor cells, other associated cells (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma efficacy and mechanisms <i>in vivo</i> and <i>in vitro</i>. The strong anti-glioma efficacy could attribute to the accumulation in glioma site and the regulation of tumor microenvironment with depletion of TAMs, inhibition of VMs, and elimination of CSCs.</p

Supplementary table: Eliminating drug target interference withspecific antibody or its F(ab?)2 fragment inthe bridging immunogenicity assay

Background: DB-1003 is a humanized anti-IgE monoclonal antibody with higher affinity than omalizumab. In the affinity capture elution (ACE)-based bridging electrochemiluminescent immunoassay (ECLIA) for antibodies to DB-1003, monkey serum IgE caused false-positive results. Materials & methods: The target specific antibody or its F(ab?)2 fragment was used to mitigate drug target interference in an ACE-based bridging ECLIA for the detection of anti-DB-1003 antibodies. Results: The sensitivity of the developed assay was at least 100 ng/ml. When the ADA concentration was 250 ng/ml, the assay tolerated at least 20.0 μg/ml of the monkey IgE. Conclusion: Incorporating the target-specific antibody or its F(ab?)2 mfragment can overcome the interference from monkey serum IgE in ACE-based bridging ECLIA for anti- DB-1003 antibody detection.</p