bims-mricoa 2021-09-05 papers

Issue of 2021‒09‒05
four papers selected by
Merve Yavuz
Bilkent University

Nanoscale. 2021 Sep 02. 13(34): 14552-14571

Unveiling the role of surface, size, shape and defects of iron oxide nanoparticles for theranostic applications.

Iron oxide nanoparticles (IONPs) are well-known contrast agents for MRI for a wide range of sizes and shapes. Their use as theranostic agents requires a better understanding of their magnetic hyperthermia properties and also the design of a biocompatible coating ensuring their stealth and a good biodistribution to allow targeting of specific diseases. Here, biocompatible IONPs of two different shapes (spherical and octopod) were designed and tested in vitro and in vivo to evaluate their abilities as high-end theranostic agents. IONPs featured a dendron coating that was shown to provide anti-fouling properties and a small hydrodynamic size favoring an in vivo circulation of the dendronized IONPs. While dendronized nanospheres of about 22 nm size revealed good combined theranostic properties (r2 = 303 mM s-1, SAR = 395 W gFe-1), octopods with a mean size of 18 nm displayed unprecedented characteristics to simultaneously act as MRI contrast agents and magnetic hyperthermia agents (r2 = 405 mM s-1, SAR = 950 W gFe-1). The extensive structural and magnetic characterization of the two dendronized IONPs reveals clear shape, surface and defect effects explaining their high performance. The octopods seem to induce unusual surface effects evidenced by different characterization techniques while the nanospheres show high internal defects favoring Néel relaxation for magnetic hyperthermia. The study of octopods with different sizes showed that Néel relaxation dominates at sizes below 20 nm while the Brownian one occurs at higher sizes. In vitro experiments demonstrated that the magnetic heating capability of octopods occurs especially at low frequencies. The coupling of a small amount of glucose on dendronized octopods succeeded in internalizing them and showing an effect of MH on tumor growth. All measurements evidenced a particular signature of octopods, which is attributed to higher anisotropy, surface effects and/or magnetic field inhomogeneity induced by tips. This approach aiming at an analysis of the structure-property relationships is important to design efficient theranostic nanoparticles.

DOI: https://doi.org/10.1039/d1nr03335b

J Control Release. 2021 Aug 27. pii: S0168-3659(21)00458-2. [Epub ahead of print]

Nanoparticles modified with vasculature-homing peptides for targeted cancer therapy and angiogenesis imaging.

Elham Seyyednia, Fatemeh Oroojalian, Behzad Baradaran, Javid Shahbazi Mojarrad, Ahad Mokhtarzadeh, Hadi Valizadeh.

The two major challenges in cancer treatment include lack of early detection and ineffective therapies with various side effects. Angiogenesis is the key process in the growth, survival, invasiveness, and metastasis of many of cancerous tumors. Imaging of the angiogenesis could lead to diagnosis of tumors in the early stage and evaluation of the therapeutic responses. Angiogenic blood vessels express specific molecular markers different from normal blood vessels (in level or kind). This fact would make the tumor vasculature a suitable site to target therapeutics and imaging agents within the tumor. Surface modified nanoparticles using peptide ligands with high binding affinity to the vasculature markers, provide efficient delivery of therapeutic and imaging agents, while avoiding undesirable side effects. In this review, we discuss discoveries of various tumor targeting peptides useful for tumor angiogenesis imaging and targeted therapy with emphasis on surface modified nanomedicines using vasculature targeting peptides.

Keywords: Angiogenesis imaging; Cancer therapy; Nanoparticle; Theranostic; Tumor vasculature targeting peptides

DOI: https://doi.org/10.1016/j.jconrel.2021.08.044

ACS Synth Biol. 2021 Aug 31.

Synthetic Circuit-Driven Expression of Heterologous Enzymes for Disease Detection.

Jiang He, Lior Nissim, Ava P Soleimany, Adina Binder-Nissim, Heather E Fleming, Timothy K Lu, Sangeeta N Bhatia.

The integration of nanotechnology and synthetic biology could lay the framework for new classes of engineered biosensors that produce amplified readouts of disease states. As a proof-of-concept demonstration of this vision, here we present an engineered gene circuit that, in response to cancer-associated transcriptional deregulation, expresses heterologous enzyme biomarkers whose activity can be measured by nanoparticle sensors that generate amplified detection readouts. Specifically, we designed an AND-gate gene circuit that integrates the activity of two ovarian cancer-specific synthetic promoters to drive the expression of a heterologous protein output, secreted Tobacco Etch Virus (TEV) protease, exclusively from within tumor cells. Nanoparticle probes were engineered to carry a TEV-specific peptide substrate in order to measure the activity of the circuit-generated enzyme to yield amplified detection signals measurable in the urine or blood. We applied our integrated sense-and-respond system in a mouse model of disseminated ovarian cancer, where we demonstrated measurement of circuit-specific TEV protease activity both in vivo using exogenously administered nanoparticle sensors and ex vivo using quenched fluorescent probes. We envision that this work will lay the foundation for how synthetic biology and nanotechnology can be meaningfully integrated to achieve next-generation engineered biosensors.

Keywords: activity probes; biomarkers; cancer; nanosensors; nanotechnology; proteases; synthetic biology

DOI: https://doi.org/10.1021/acssynbio.1c00133

Acta Biochim Pol. 2021 Aug 30. 68(3): 377-383

Gene-circuit therapy on the horizon: synthetic biology tools for engineered therapeutics.

Rafał Krzysztoń, Yiming Wan, Julia Petreczky, Gábor Balázsi.

Therapeutic genome modification requires precise control over the introduced therapeutic functions. Current approaches of gene and cell therapy fail to deliver such command and rely on semi-quantitative methods with limited influence on timing, contextuality and levels of transgene expression, and hence on therapeutic function. Synthetic biology offers new opportunities for quantitative functionality in designing therapeutic systems and their components. Here, we discuss synthetic biology tools in their therapeutic context, with examples of proof-of-principle and clinical applications of engineered synthetic biomolecules and higher-order functional systems, i.e. gene circuits. We also present the prospects of future development towards advanced gene-circuit therapy.

DOI: https://doi.org/10.18388/abp.2020_5744