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Recent innovations in genome editing have enabled the precise manipulation of the genetic information of mammalians, and benefitted the development of next-generation gene therapy. Despite these advances, several barriers to the clinical translation of genome editing remain, including the intracellular delivery of genome editing machinery, and the risk of off-target editing effect. Here, we review the recent advance of spatiotemporal delivery of CRISPR/Cas9 genome editing machinery, which is composed of programmable Cas9 nuclease and a single-guide RNA (sgRNA) using stimuli-responsive nanoparticles. We discuss the specific chemistries that have been used for controlled Cas9/sgRNA delivery and intracellular release in the presence of endogenous or external signals. These methodologies can leverage biological signals found locally within disease cells, or exogenous signals administrated with spatiotemporal control, through which an improved genome editing could be achieved. We also discuss the future in exploiting these approaches for fundamental biomedical applications and therapeutic genome editing.

This Review presents polysaccharides, oligosaccharides, nucleic acids, peptides, and proteins as functional stimuli-responsive polymer scaffolds that yield hydrogels with controlled stiffness. Different physical or chemical triggers can be used to structurally reconfigure the crosslinking units and control the stiffness of the hydrogels. The integration of stimuli-responsive supramolecular complexes and stimuli-responsive biomolecular units as crosslinkers leads to hybrid hydrogels undergoing reversible triggered transitions across different stiffness states. Different applications of stimuli-responsive biomolecule-based hydrogels are discussed. The assembly of stimuli-responsive biomolecule-based hydrogel films on surfaces and their applications are discussed. The coating of drug-loaded nanoparticles with stimuli-responsive hydrogels for controlled drug release is also presented.

A strategy is presented that enables the quantitative assembly of a heterobimetallic [PdPtL4 ]4+ cage. The presence of two different metal ions (PdII and PtII ) with differing labilities enables the cage to be opened and closed selectively at one end upon treatment with suitable stimuli. Combining an inert PtII tetrapyridylaldehyde complex with a suitably substituted pyridylamine and PdII ions led to the assembly of the cage. 1 H and DOSY NMR spectroscopy and ESI mass spectrometry data were consistent with the quantitative formation of the cage, and the heterobimetallic structure was confirmed using single-crystal X-ray crystallography. The structure of the host-guest adduct with a 2,6-diaminoanthraquinone guest molecule was determined. Addition of N,N'-dimethylaminopyridine (DMAP) resulted in the formation of the open-cage [PtL4 ]2+ compound and [Pd(DMAP)4 ]2+ complex. This process could then be reversed, with the reformation of the cage, upon addition of p-toluenesulfonic acid (TsOH).

Purely organic materials showing room temperature phosphorescence (RTP) and ultralong RTP (OURTP) have recently attracted much attention. However, it is challenging to integrate circularly polarized luminescence (CPL) into RTP/OURTP. Here, we show a strategy to realize CPL-active OURTP (CP-OURTP) by binding an achiral phosphor group directly to the chiral center of an ester chain. Engineering of this flexible chiral chain enables efficient chirality transfer to carbazole aggregates, resulting in strong CP-OURTP with a lifetime of over 0.6 s and dissymmetry factor of 2.3×10-3 after the conformation regulation upon photo-activation. The realized CP-OURTP is thus stable at room temperature but can be deactivated quickly at 50 °C to CP-RTP with high CPL stability during the photo-activation/thermal-deactivation cycles. Based on this extraordinary photo/thermal-responsive and highly reversible CP-OURTP/RTP, a CPL-featured lifetime-encrypted combinational logic device has been successfully established.

A new multi-sensor material based on helical copolymers showing the chiral conflict effect have been prepared. It can successfully detect and identify diverse metal cations in solution. The design of this material has taken into account not only the opposite helical senses induced by the two chiral monomers in the copolymer, but also their dynamic behavior. The induced helical sense can thus be enhanced, diminished, or inverted by interaction with different stimuli (that is, metal ions). Thus, depending on both the copolymer compositions (such as monomer ratios and absolute configurations) and the nature of the metal ion, the response of these dynamic helical copolymers to adopt a single-handed P or M helix is unique, making it possible not only to detect their presence, but also to identify them individually. New multi-sensors materials based and inspired on this effect should arise in the future choosing appropriate monomers and stimuli.

Featuring high biocompatibility, the emerging field of gas therapy has attracted extensive attention in the medical and scientific communities. Currently, considerable research has focused on the gasotransmitter nitric oxide (NO) owing to its unparalleled dual roles in directly killing cancer cells at high concentrations and cooperatively sensitizing cancer cells to other treatments for synergistic therapy. Of particular note, recent state-of-the-art studies have turned our attention to the chemical design of various endogenous/exogenous stimuli-responsive NO-releasing nanomedicines and their biomedical applications for on-demand NO-sensitized synergistic cancer therapy, which are discussed in this Minireview. Moreover, the potential challenges regarding NO gas therapy are also described, aiming to advance the development of NO nanomedicines as well as usher in new frontiers in this fertile research area.

A pivotal guest role: a new porphyrin polymer, poly(PorZn⋅DD) (pink/purple), composed of a porphyrinatozinc and a porphyrin double-decker complex as a repeating unit was synthesized. In poly(PorZn⋅DD), porphyrinatozinc complexes recognize a divalent amine (tan/red) to induce an intramolecular pivoting motion through the rotation of porphyrin double-decker complexes and the polymer undergoes shortening and compaction.