Outer-Frame-Degradable Nanovehicles Featuring Near-Infrared Dual Luminescence for in Vivo Tracking of Protein Delivery in Cancer Therapy

Abstract

In vivo monitoring of cargo protein delivery is critical for understanding the pharmacological efficacies and mechanisms during cancer therapy, but it still remains a formidable challenge because of the difficulty in observing nonfluorescent proteins at high resolution and sensitivity. Here we report an outer-frame-degradable nanovehicle featuring near-infrared (NIR) dual luminescence for real-time tracking of protein delivery in vivo. Upconversion nanoparticles (UCNPs) and fluorophore-doped degradable macroporous silica (DS) with spectral overlap were coupled to form a core–shell nanostructure as a therapeutic protein nanocarrier, which was eventually enveloped with a hyaluronic acid (HA) shell to prevent protein leakage and for recognizing tumor sites. The DS layer served as both a container to accommodate the therapeutic proteins and a filter to attenuate upconversion luminescence (UCL) of the inner UCNPs. After the nanovehicles selectively accumulated at tumor sites and entered cancer cells, intracellular hyaluronidase (HAase) digested the outermost HA protective shell and initiated the outer frame degradation-induced protein release and UCL restoration of UCNPs in the intracellular environment. Significantly, the biodistribution of the nanovehicles can be traced at the 710 nm NIR fluorescence channel of DS, whereas the protein release can be monitored at the 660 nm NIR fluorescence channel of UCNPs. Real-time tracking of protein delivery and release was achieved in vitro and in vivo by NIR fluorescence imaging. Moreover, in vitro and in vivo studies manifest that the protein cytochrome c-loaded nanovehicles exhibited excellent cancer therapeutic efficacy. This nanoplatform assembled by the outer-frame-degradable nanovehicles featuring NIR dual luminescence not only advances our understanding of where, when, and how therapeutic proteins take effect in vivo but also provides a universal route for visualizing the translocation of other bioactive macromolecules in cancer treatment and intervention.

Nanomediator–Effector Cascade Systems for Amplified Protein Kinase Activity Imaging and Phosphorylation‐Induced Drug Release In Vivo

“…BHQ1doped SNPs (Q1-SNPs) were first prepared and activated by 3-azidopropyltrimethoxysilane,a nd then tethered with propargyl-teminated PKA substrate peptide (sub-peptide) via copper (I)-catalyzed azide-alkyne cycloaddition (pQ1-SNPs) (Figure S2a). [44] To configure the interfaces that can be actuated by sub-peptide phosphorylation, the mediator DNAs trands were further assembled onto the pQ1-SNPs via electrostatic interaction (NMs,S cheme S1a and Figure S3a). After the surface engineering with cancer cell membrane,t he resultant mNMs showed a1 0-nm thick layer around the solid SNPs in the transmission electron microscopy (TEM) and high-angle annular dark-field scanning transmission microscopy (HAADF-STEM) images (Figure 1a).…”

Boosting the Energy Migration Upconversion through Inter-Shell Energy Transfer in Tb 3+ -Doped Sandwich Structured Nanocrystals

“…These discoveries provide a deeper mechanistic understanding of the fundamental EMU process in lanthanide NCs involving energy management 3,[68][69][70][71][72][73] on the nanometer-length scale, which may pave a new way to control or modify the upconversion emissions of lanthanide NCs and consequently contribute to their frontier bioapplications. [74][75][76][77][78][79][80][81]…”

Nanotechnology for Hepatocellular Carcinoma: From Surveillance, Diagnosis to Management

“…[ 83,84 ] NIR and microwaves can also cause deep tissue to heat up and dissolve solid tumors, so they can be applied to reduce the trauma caused by surgery. [ 85–88 ] Magnetic field requires the carrier to be magnetic and stable in humoral environment, so it has a broad prospect in comprehensive treatment of elements such as manganese and iron. [ 89,90 ] Combining the physical and chemical properties of nanomaterials with traditional chemotherapeutic drugs has brought back chances of systematic therapies that were not so suitable for early solid HCC tumors.…”