Controlling Cancer Cell Fate Using Localized Biocatalytic Self-Assembly of an Aromatic Carbohydrate Amphiphile

Abstract

We report on a simple carbohydrate amphiphile able to self-assemble into nanofibers upon enzymatic dephosphorylation. The self-assembly can be triggered by alkaline phosphatase (ALP) in solution or in situ by the ALP produced by osteosarcoma cell line, SaOs2. In the latter case, assembly and localized gelation occurs mainly on the cell surface. The gelation of the pericellular environment induces a reduction of the SaOs2 metabolic activity at an initial stage (≤7 h) that results in cell death at longer exposure periods (≥24 h). We show that this effect depends on the phosphatase concentration, and thus, it is cell-selective with prechondrocytes ATDC5 (that express ∼15-20 times lower ALP activity compared to SaOs2) not being affected at concentrations ≤1 mM. These results demonstrate that simple carbohydrate derivatives can be used in an antiosteosarcoma strategy with limited impact on the surrounding healthy cells/tissues.

Negatively Charged Lipid Membranes Catalyze Supramolecular Hydrogel Formation

“…[1][2][3][4] Furthermore, the groups of Rao, Xu and others have recently shown that enzymatic activation of synthetic self-assembling molecules in a cellular environments find promising applications as imaging and therapeutic agents. [5][6][7][8][9][10][11][12][13] A key challenge in this field is the spatial control over self-assembly. To achieve this, the self-assembling species needs to be formed in the vicinity of the region of interest, after which self-assembly into aggregates effectively immobilizes the formed material.…”

Enzyme‐Instructed Intracellular Molecular Self‐Assembly to Boost Activity of Cisplatin against Drug‐Resistant Ovarian Cancer Cells

“…The genome analysis according to The Cancer Genome Atlas (TCGA) indicates the amplification of CES in certain tumors (e.g., breast and ovarian cancer) ( Figure S23), which not only supports the observation in this work, but also provides useful guidance for treating other cancers based on this approach. This work, together with other emerging evidence, [6][7][8][9][10]12] indicates that enzyme-instructed self-assembly promises a new way for developing combination therapy for cancer treatment. Other than cisplatin, carboplatin has been used as the preferred platinum-based drug [20] and we will use carboplatin for our future work.…”

“…[8] Recently, Maruyama et al, [9] Pires and Ulijn, [10] Yang et al, [11] and Wells [12] also reported inhibition of cancer cells by nanofibers formed by the self-assembly of small molecules. The exceptional selectivity [8] and fundamentally new mechanisms [7,13] of the molecular nanofibers against cancer cells encouraged us to explore the utilization of enzyme-instructed intracellular molecular self- …”

Sequentially Programmable and Cellularly Selective Assembly of Fluorescent Polymerized Vesicles for Monitoring Cell Apoptosis

“…Compared to the general way that self‐assembled nanoagents were beforehand produced in inanimate environments, the introduction of controlled self‐assembly into living things paves an alternative avenue to generate smart biomedical materials 10, 11, 12, 13. In these examples, molecular building blocks undergo self‐assembly following initial cellular uptake and subcellular activation 14, 15, 16. From the viewpoint of diagnostics, Rao's group imparted a biocompatible/bioorthogonal cyclization‐mediated in situ self‐assembly of small‐molecule probes for imaging protease activity both in vitro and in vivo 17, 18.…”

“…Enzymes, as an endogenous stimulus with desired specificity, have been commonly used to convert nonassembling precursors into self‐assembling blocks in living things,14, 15, 16, 23 which could alternatively achievable by some biocompatible exogenous stimuli too. However, self‐assembly under integrated control of both endogenous and exogenous stimuli, especially in the form of sequential input, is unprecedented and ultimately challenging.…”