Antibody‐Functionalized Porous Silicon Nanoparticles for Vectorization of Hydrophobic Drugs

Abstract

We describe the preparation of biodegradable porous silicon nanoparticles (pSiNP) functionalized with cancer cell targeting antibodies and loaded with the hydrophobic anti-cancer drug camptothecin. Orientated immobilization of the antibody on the pSiNP is achieved using novel semicarbazide based bioconjugate chemistry. To demonstrate the generality of this targeting approach, the three antibodies MLR2, mAb528 and Rituximab are used, which target neuroblastoma, glioblastoma and B lymphoma cells, respectively. Successful targeting is demonstrated by means of flow cytometry and immunocytochemistry both with cell lines and primary cells. Cell viability assays after incubation with pSiNPs show selective killing of cells expressing the receptor corresponding to the antibody attached on the pSiNP.

Targeted drug delivery using genetically engineered diatom biosilica

“…Furthermore, antibody-mediated targeting of tumour cells was demonstrated by using an antibody that recognizes an antigen on an adherent cancer cell line. Attachment of anti-p75NTR-labelled GB1-biosilica frustules to SH-SY5Y neuroblastoma cells 34 , which express p75NTR, but not to control fibroblasts demonstrated the selective cell targeting of the frustules in an adherent cell system. Therefore, functionalized diatom biosilica can selectively target both adherent and suspension tumour cells.…”

A Brief Overview of Hyperthermia in Cancer Treatment

“…However, most of the electrolytes are uselessly heated up because the heat has to be concentrated on the tumor-cells and exclusively on their membranes to damage them decisional. This request needs a higher preciosity, addressing the nanoparticles selectively on the surface of the tumor-cells, which can be made by antibody-nanoparticle conjugates [39]. It releases of therapeutic targets at the connected malignant cells while minimizing off-target side effects.…”

Antibody-Targeted Nanoparticles for Cancer Treatment

“…Targeting EGFR has also shown invivo efficacy in a range of models. For example, in delivery of paclitaxel-loaded polymeric NPs to lung tumours [36], camptothecin loaded porous silica NPs to a range of EGFR over-expressing tumours including glioblastoma [68] and adriamycin encapsulated polymer-lipid NPs to hepatocellular carcinoma [65]. In this final example, there was also evidence suggesting that both the antibody and adriamycin were contributing to the observed cytotoxicity [65].…”

“…NPs were shown to selectively internalise in cells overexpressing HIF-1α and paclitaxel mediated cytotoxicity was shown to be specific towards HIF-1α expressing cells.Other targets investigated for controlled delivery of drug-loaded NPs include the cell surface glycoprotein and tumour marker carcinoembryonic antigen (CEA) and the p75 neurotrophin receptor (NTR) [68].NTR is a member of the tumour necrosis factor (TNF) superfamily, which has a role in cell death and is overexpressed in a number of malignancies including sarcoma and malignant melanoma [81]. Drug-loaded NPs have also been targeted using SM5-1, a mouse-human chimeric antibody which is highly specific to the SM5-1 binding protein, a target known to be overexpressed in a number of cancers including hepatocellular carcinoma (HCC), melanoma and breast cancer.…”