Evaluation of a Tumor-Targeting Oligosaccharide Nanosystem in BNCT on an Orthotopic Hepatocellular Carcinoma Model

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD–integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy

Pt/DOX Nanomotors Enhance Penetration in the Deep Tumor by Positive Chemotaxis

Inefficient tumor penetration caused by the characteristics of tumor microenvironments is a primary obstacle to improving drug delivery efficiency, which restricts the chemotherapy drug efficacy. One such promising idea is to construct micro/nanomotors (MNMs) as an effective delivery vehicle by way of producing autonomous motion and converting exogenous stimuli or external energies from the surrounding environment into mechanical forces. In this research, the Pt/DOX nanomotor was prepared, and the enhanced diffusion and positive chemotaxis driven by substrates were verified in vitro, proof of the enhanced cellular uptake and deep penetration of Pt/DOX. As a novel nanovehicle, Pt/DOX potentially provides an intriguing approach to foster the tumor-deep penetration and enhance the drug delivery efficiency

Additional file 1 of Therapeutic nucleus-access BNCT drug combined CD47-targeting gene editing in glioblastoma

Additional file 1. Concludes the results of the characterization of multifunctional nanoliposomes and DOX-CB and the results of cellular distribution and the cell viability of DOX-CB. The results of additional animal experiments such as evaluation of the GL261-orthotopicglioma in the C57BL/6 mouse model and HE staining of different organs

Association between <i>ERCC1</i> rs3212986 and <i>ERCC2</i> rs238406 polymorphisms and BPDE-DNA adducts stratified by age.

<p>Association between <i>ERCC1</i> rs3212986 and <i>ERCC2</i> rs238406 polymorphisms and BPDE-DNA adducts stratified by age.</p

<i>ERCC1</i>, <i>ERCC2</i> genotypes and BPDE-DNA adducts levels (, n = 282).

a<p><i>P</i> value was obtained using the LSD test or t-test analysis comparing with reference.</p>b<p><i>P</i> value was obtained using one-way ANVOA.</p

<i>ERCC1</i>, <i>ERCC2</i> haplotypes and BPDE-DNA adduct levels.

<p>Other haplotypes with frequency less than 0.03.</p>c<p><i>P</i> value was obtained using X² test.</p

Comparison of DNA damage caused by B[a]P in different combined minor alleles of ERCC1 rs3212986 and ERCC2 rs238406.

<p>We selected the participants carrying different ERCC1 rs3212986 and ERCC2 rs238406 genotypes and analyzed their induced DNA damage levels induced by B[a]P using the modified comet assay. The damage levels were evaluated by the tail olive moment ratio, tail area ratio and the combined holistic marking respectively. The relationship between the combined minor alleles of ERCC1 rs3212986 and ERCC2 rs238406 and the effect on the repair efficacy of the DNA damage level caused by B[a]P were evaluated. Interestingly, we found following the increasing copies of the combined minor alleles, a reduced DNA repair capacity had been found in the tail olive moment ratio, tail area ratio and the combined holistic marking. (<i>P</i><0.01).</p

BPDE-DNA adducts levels and characteristics of study population (, n = 282).

a<p><i>P</i> value was obtained using the LSD test or t-test analysis comparing with reference.</p>b<p><i>P</i> value was obtained using one-way ANVOA.</p

Association between <i>ERCC1</i> rs3212986 and <i>ERCC2</i> rs238406 polymorphism and BPDE-DNA adducts stratified by smoking index.

<p>Smoking index 1: never smoking;</p><p>Smoking index = average cigarette numbers/day×years.</p

Chromatograms of blank, DNA, BPDE and DNA+BPDE solutions using HPLC-UV detection.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060006#pone-0060006-g001" target="_blank">Figure 1</a> reflects the representive HPLC readouts. We used the Chromatograms to detect BPDE-DNA adducts level. The retention time of 9.38 minute was identified to be BPDE-DNA adducts.</p