bims-mricoa 2022-03-13 papers

Issue of 2022–03–13
three papers selected by
Merve Yavuz, Bilkent University

ACS Synth Biol. 2022 Mar 08.

Reprogramming Synthetic Cells for Targeted Cancer Therapy.

Boon Lim, Yutong Yin, Hua Ye, Zhanfeng Cui, Antonis Papachristodoulou, Wei E Huang.

Advances in synthetic biology enable the reprogramming of bacteria as smart agents to specifically target tumors and locally release anticancer drugs in a highly controlled manner. However, the bench-to-bedside translation of engineered bacteria is often impeded by genetic instability and the potential risk of uncontrollable replication of engineered bacteria inside the patient. SimCells (simple cells) are chromosome-free bacteria controlled by designed gene circuits, which can bypass the interference of the native gene network in bacteria and eliminate the risk of bacterial uncontrolled growth. Here, we describe the reprogramming of SimCells and mini-SimCells to serve as "safe and live drugs" for targeted cancer therapy. We engineer SimCells to display nanobodies on the surface for the binding of carcinoembryonic antigen (CEA), which is an important biomarker found commonly in colorectal cancer cells. We show that SimCells and mini-SimCells with surface display of anti-CEA nanobody can specifically bind CEA-expressing Caco2 cancer cells in vitro while leaving the non-CEA-expressing SW80 cancer cells untouched. These cancer-targeting SimCells and mini-SimCells induced cancer cell death in vitro by compromising the plasma membrane of cancer cells. The cancer-killing effect can be further enhanced by an aspirin/salicylate inducible gene circuit that converts salicylate into catechol, a potent anticancer. This work highlights the potential of SimCells and mini-SimCells for targeted cancer therapy and lays the foundation for the application of synthetic biology to medicine.

Keywords: I-CeuI endonuclease; SimCells; bacterial therapy; cancer; catechol; chromosome-free; drug delivery; minicells; synthetic biology

DOI: https://doi.org/10.1021/acssynbio.1c00631

Nanoscale. 2022 Mar 07.

Iron oxide nanoparticles as a drug carrier reduce host immunosuppression for enhanced chemotherapy.

Benqing Zhou, Jinxing Liu, Lu Wang, Meng Wang, Chong Zhao, Haoyu Lin, Yuanke Liang, Rheal A Towner, Wei R Chen.

Chemotherapy is still regarded as the main modality for cancer treatment. However, it often suppresses the host immune system, resulting in limited therapeutic effects. It is desirable to design a novel chemotherapeutic agent to reduce the level of immunosuppression. Herein, we designed bovine serum albumin (BSA)-bioinspired iron oxide nanoparticles (IONPs) as a nanocarrier to load anticancer drug mitoxantrone (MTX) for enhanced chemotherapy of orthotopic breast cancer. The treatment with IONPs@BSA-MTX complexes increased CD3+CD4+ and CD3+CD8+ T lymphocytes more than free MTX. The complexes effectively restored the host immune system and exhibited a better anticancer efficacy than free MTX. It was worth noting that the BSA-inspired IONPs were a satisfactory contrast agent for magnetic resonance imaging of tumors and lymph nodes. Our work provides a novel strategy for enhanced chemotherapy with low levels of immunosuppression in the treatment of breast cancer and other cancers.

DOI: https://doi.org/10.1039/d1nr07750c

Polymers (Basel). 2022 Feb 28. pii: 986. [Epub ahead of print]14(5):

Protein-Based Hydrogels: Promising Materials for Tissue Engineering.

Niyousha Davari, Negar Bakhtiary, Mehran Khajehmohammadi, Soulmaz Sarkari, Hamidreza Tolabi, Farnaz Ghorbani, Behafarid Ghalandari.

The successful design of a hydrogel for tissue engineering requires a profound understanding of its constituents' structural and molecular properties, as well as the proper selection of components. If the engineered processes are in line with the procedures that natural materials undergo to achieve the best network structure necessary for the formation of the hydrogel with desired properties, the failure rate of tissue engineering projects will be significantly reduced. In this review, we examine the behavior of proteins as an essential and effective component of hydrogels, and describe the factors that can enhance the protein-based hydrogels' structure. Furthermore, we outline the fabrication route of protein-based hydrogels from protein microstructure and the selection of appropriate materials according to recent research to growth factors, crucial members of the protein family, and their delivery approaches. Finally, the unmet needs and current challenges in developing the ideal biomaterials for protein-based hydrogels are discussed, and emerging strategies in this area are highlighted.

Keywords: interaction; protein structures; protein-based hydrogel; tissue engineering; unfolding

DOI: https://doi.org/10.3390/polym14050986