Transcription-Factor-Induced Aggregation of Biomimetic Oligonucleotide-b-Protein Micelles

Abstract

Polymeric micelles and especially those based on natural diblocks are of particular interest due to their advantageous properties in terms of molecular recognition, biocompatibility, and biodegradability. We herein report a facile and straightforward synthesis of thermoresponsive elastin-like polypeptide (ELP) and oligonucleotide (ON) diblock bioconjugates, ON-b-ELP, through copper-catalyzed azide–alkyne cycloaddition. The resulting thermosensitive diblock copolymer self-assembles above its critical micelle temperature (CMT ∼30 °C) to form colloidally stable micelles of ∼50 nm diameter. The ON-b-ELP micelles hybridize with an ON complementary strand and maintain their size and stability. Next, we describe the capacity of these micelles to bind proteins, creating more complex structures using the classic biotin–streptavidin pairing and the specific recognition between a transcription factor protein and the ON strand. In both instances, the micelles are intact, form larger structures, and retain their sensitivity to temperature.

Thermoresponsive Core-cross-linked Nanoparticles from HA-b-ELP Diblock Copolymers

“…For several years, our group has been particularly interested in the use of elastin-like polypeptides (ELPs), in particular, for the design of self-assembled NPs. − ELPs are biosynthetic polymers presenting lower critical solution temperature (LCST) phase transition properties in aqueous media. − Soluble at a specific concentration below the cloud point temperature ( T cp ), ELP chains hydrophobically collapse above the T cp . Regarding their major assets such as biocompatibility, biodegradability, controlled sequence over synthetic polymers, ease of production in heterologous hosts, and purification, ELPs are excellent candidates for the design of self-assembled DDS. , Fusion of ELP blocks with different LCSTs or conjugation of an ELP to another (macro)­molecule can yield macromolecules with controllable amphiphilic character and thermally driven and reversible self-assembly or disassembly properties .…”

Unravelling the Mechanism of Elastin-like Polypeptide-Enzyme Fusion Stabilization in Organic Solvents

“…ELPs display a low critical solution temperature (LCST) and undergo a reversible phase separation at their transition temperature. − Moreover, ELPs are responsive to various stimuli, including pH and ionic strength, and these characteristics have been employed to create diverse nanostructures. , This versatility enables ELP fusions with functional proteins, making them suitable for applications in wound healing, drug delivery, and other therapeutic purposes. − Their temperature responsiveness has been employed to create microarchitectures that exhibit LCST phase behavior, leading to the formation of distinct hollow microshell emulsions that can be stabilized through UV cross-linking. In addition, a self-assembling, ELP-oligonucleotide diblock has been synthesized to form thermosensitive stable micellar structures . Furthermore, this stimulus has been harnessed to develop thermosensitive hydrogels for potential biomedical use. , pH-sensitive ELP condensates were engineered by adjusting the ratio of charged and hydrophobic guest residues.…”