In Situ Monitoring Intracellular Structural Change of Nanovehicles through Photoacoustic Signals Based on Phenylboronate-Linked RGD-Dextran/Purpurin 18 Conjugates

Abstract

The stimuli-responsive polymeric nanocarriers have been studied extensively, and their structural changes in cells are important for the controlled intracellular drug release. The present work reported RGD-dextran/purpurin 18 conjugates with pH-responsive phenylboronate as spacer for monitoring the structural change of nanovehicles through ratiometric photoacoustic (PA) signal. Phenylboronic acid modified purpurin 18 (NPBA-P18) could attach onto the RGD-decorated dextran (RGD-Dex), and the resulting RGD-Dex/NPBA-P18 (RDNP) conjugates with different molar ratios of RGD-Dex and NPBA-P18 were prepared. When the moles of NPBA-P18 were equivalent to more than triple of RGD-Dex, the single-stranded RDNP conjugates could self-assemble into nanoparticles in aqueous solution due to the fairly strong hydrophobicity of NPBA-P18. The pH-responsive aggregations of NPBA-P18 were investigated by UV-vis, fluorescence, and circular dichroism spectra, as well as transmission electron microscope. Based on distinct PA signals between monomeric and aggregated state, ratiometric PA signal of I/I could be presented to trace the structural change progress. Compared with RDNP single chains, the nanoparticles exhibited effective cellular internalization through endocytosis pathway. Furthermore, the nanoparticles could form well-ordered aggregates responding to intracellular acidic environment, and the resulting structural change was also monitored by ratiometric PA signal. Therefore, the noninvasive PA approach could provide a deep insight into monitoring the intracellular structural change process of stimuli-responsive nanocarriers.

Site‐Specific Construction of Long‐Term Drug Depot for Suppression of Tumor Recurrence

“…Nanomaterials as drug carriers can escape from the reticuloendothelial system (RES) and accumulate at tumor sites through targeting effect . Recently, our group focus on the transformable nanomaterials that show high accumulation and retention in targeted sites because of assembly/aggregation induced retention (AIR) effect of peptide nanofibers (NFs) .…”

Ratiometric optical nanoprobes enable accurate molecular detection and imaging

“…The reversible absorption spectral change provided a potential method for fabricating ratiometric PA nanosensors for real-time detection of temperature. Similarly, the design concept of stimuli-responsive PA nanoswitches has also been employed for ratiometric imaging and monitoring of intracellular pH 359 and caspase-1 activity. 360…”

Programmable Construction of Peptide‐Based Materials in Living Subjects: From Modular Design and Morphological Control to Theranostics

“…In addition to π–π stacking, the hydrophobic interaction is also reported as a driving force of self‐assembly. π‐Conjugated small molecules or peptides with highly ordered mixed‐stack π‐electron donor–acceptor (D–A) domains have been interesting researchers in the development of solution‐processable semiconducting materials . A peptide including a responsive module and a penetrating module is linked onto thermoresponsive polymer–peptide conjugates (PPCs) with an isothermal phase‐transition property.…”

“…Hydrophobicity‐sensitive probes, such as NBD, is utilized for direct imaging of the membrane dynamics of living cells when conjugated with peptides and activated by phosphatases. With the same lighting‐up mechanism, the thermosensitive peptide–polymer conjugated with NBD can be molecularly tailored by caspase‐3 inside cells to induce aggregation, which is named as endogenous stimuli‐induced aggregation (eSIA) . The eSIA for caspase‐3 provides us with a potential tool for real‐time monitoring of chemotherapy with quantitative reflection of the therapeutic effect.…”