Targeted drug delivery using genetically engineered diatom biosilica

Abstract

The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells. The diatom Thalassiosira pseudonana is genetically engineered to display an IgG-binding domain of protein G on the biosilica surface, enabling attachment of cell-targeting antibodies. Neuroblastoma and B-lymphoma cells are selectively targeted and killed by biosilica displaying specific antibodies sorbed with drug-loaded nanoparticles. Treatment with the same biosilica leads to tumour growth regression in a subcutaneous mouse xenograft model of neuroblastoma. These data indicate that genetically engineered biosilica frustules may be used as versatile 'backpacks' for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites.

Neuroblastoma: Genetic, Epigenetic Mechanisms and Targeted Therapy Approaches: Review

“…94 Nöroblastom hücrelerine ilaç dağıtımını hedeflemek, diyatomlar gibi biyolojik nanoporoz moleküllerle sağlanabilmekte, böylece sağlıklı hücrelere olan zarar en aza indirilebilmektedir. 95 Kümelenmiş düzenli aralıklı kısa palindromik tekrarlar [Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)] ve Cas9 CRISPRilişkili protein-9 nükleaz [CRISPR-associated protein-9 nuclease] sistemleri, moleküler tıp uygulamaları için büyük potansiyele sahip, önemli genom düzenleme araçlarıdır. Çalışmalar, patogenezde rol oynayan mekanizmaları açıklığa kavuşturmayı ve hedefe yönelik tedavileri geliştir-meyi amaçlamaktadır.…”

Cancer in North Cyprus: 2. Biomedical Research Activities

“…Such structures could enable regeneration or replacement of body parts lost to infection, accident, or disease (47). A further development is silicon NPs with polymer-like strands holding an anti-cancer drug; these degrade upon entering the cells and discharge the contents (48). Research also aims to develop NPs to target bacteria including gold NPs irradiated with infrared light and iron oxide (FeO) NPs coated with polymer (49).…”

Editing of the urease gene by CRISPR-Cas in the diatomThalassiosira pseudonana

“…It is a model centric diatom with a sequenced genome (first eukaryotic marine phytoplankton to be sequenced [2]) and wellestablished transformation systems [19,20]. The genus has multiple biotechnology applications [8,21,22], and although gene silencing has been established, a method to easily and efficiently knock-out and edit genes and the entire genome would be highly advantageous. The genus Thalassiosira is among the top 10 genera of diatoms in the World's Ocean in terms of ribotype (V9 of 18S) diversity and abundance [23] and the species T. pseudonana is a model for understanding the mechanisms behind silicification [24][25][26].…”