Covalent Amide-Bonded Nanoflares for High-Fidelity Intracellular Sensing and Targeted Therapy: A Superstable Nanosystem Free of Nonspecific Interferences

Abstract

A nanoflare, a conjugate of Au nanoparticles (NPs) and fluorescent nucleic acids, is believed to be a powerful nanoplatform for diagnosis and therapy. However, it highly suffers from the nonspecific detachment of nucleic acids from the AuNP surface because of the poor stability of Au−S linkages, thereby leading to the false-positive signal and serious side effects. To address these challenges, we report the use of covalent amide linkage and functional Au@graphene (AuG) NP to fabricate a covalent conjugate system of DNA and AuG NP, label-rcDNA-AuG. Covalent coating of abundant amino groups (−NH 2 ) onto the graphitic shell of AuG NP efficiently facilitates the coupling with carboxyl-labeled capture DNA sequences through simple, but strong, amide bonds. Importantly, such an amidebonded nanoflare possesses excellent stability and anti-interference capability against the biological agents (nuclease, DNA, glutathione (GSH), etc.). By accurately monitoring the intracellular miR-21 levels, this covalent nanoflare is able to identify the positive cancer cells even in a mix of cancer and normal cells. Moreover, it allows for efficient photodynamic therapy of the targeted cancer cells with minimized side effects on normal cells. This work provides a facile approach to develop a superstable nanosystem showing promising potential in clinical diagnostics and therapy.

Compute-and-Release Logic-Gated DNA Cascade Circuit for Accurate Cancer Cell Imaging

“…Next, we verified the cell recognition ability of the CAR-CHA-HCR circuit with MCF-7 (human breast cancer breast cancer cell line) as the targeted cells, which expressed high levels of miR-21 and low levels of miR-892b. ,,,− Figure S17 demonstrates that the red fluorescence in MCF-7 cells was gradually brightened after incubation with CAR-CHA-HCR circuits for 120 min, suggesting an optimized incubation time (120 min) for the following cell testing. In Figure A, a bright red fluorescence was shown in MCF-7 cells, indicating that “ON” fluorescence signals of the CAR-CHA-HCR circuit could be activated in targeted cells as expected.…”

Progress of Nanomaterials in Photodynamic Therapy Against Tumor

“…However, the stability of the Au-S bond is poor, and the DNA is non-specifically detached from the surface of AuNPs, resulting in false positive signals and severe side effects. Zhang et al used a simple and highly stable amide bond (-CO-NH-) instead of the Au-S bond and combined the DNA probe on Au@graphene (AuG) to prepare Label-rcDNA-AuG Zhang J. et al (2021) . Label-rcDNA-AuG could improve the anti-interference ability of nanoprobes against nucleases, GSH and other biological agents.…”

“…One important subcategory of gated drug-loaded NMOF includes stimulus-responsive nucleic acid-locked drug-loaded NMOF, gaining from the remarkable versatility of nucleic acid sequences to generate recognition elements and structural elements ( Zhao et al, 2020 ). For this, Zhang et al designed and synthesized the UIO-66 metal-organic framework nanoparticles (NMOF) modified with aptamer-functionalized DNA tetrahedra functionalized by ATP-aptamer or VEGF-aptamer could be loaded with the DOX, which responded to ATP or VEGF to release the drug Zhang S. et al (2021) . They utilized VEGF-responsive tetrahedral-gated NMOFs to load the photosensitizer Zn (II) protoporphyrin IX (Zn (II)-PPIX) to synthesize Zn (II)-PPIX/G-quadruplex VEGF aptamer-tetrahedral nanostructures.…”

“…In addition, multifunctional NPs loading with chemotherapeutic drugs and PSs are also a promising method for effective tumor combination therapy. Zhang’s group had designed and synthesized a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M (A) D@PI-PEG-RGD) ( Figure 9 ) Zhang Z. et al (2021) . DOX and NH 4 HCO 3 were loaded into MSNs pores, MSNs was coated with polydopamine (PDA) layer, and then ICG as a photothermal and photodynamic agent was loaded onto the PDA layer surface, finally the nanoparticles were modified with polyethylene glycol (PEG) and RGD.…”

“…In addition, the acidic microenvironment accelerates the release of DOX by breaking down NH 4 HCO 3 , which combine chemotherapy, PTT and PDT to enhance the therapeutic effect. Reproduced with permission from ( Zhang J. et al, 2021 ).…”