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Figure 1. 

Schematic descriptions of TAC technology, from molecular components, therapeutic applications, to delivery strategies.

Figure 2. 

The action mechanisms of different TAC molecules, including PROTAC, LYTAC, AUTOTAC, RiboTAC, and DEPTAC, for targeting degradation of intracellular protein, membrane and extracellular protein, protein aggregate, RNA, and dephosphorylation.

Figure 3. 

Properties of the POI ligand, degradation-inducing ligand, and linker within TAC molecules.

Figure 4. 

Schematic illustration of PROTAC^[77] and LYTAC^[6] applications in brain tumor therapy. Reprinted with permission from Ref.^[77]. Copyright 2025 Springer Nature. Reprinted with permission from Ref.^[6]. Copyright 2025 Springer Nature.

Figure 5. 

By inducing the degradation of POIs, TAC serves as an effective approach for treating NDs. These POIs include membrane proteins, cytoplasmic aggregates, and damaged organelles.

Figure 6. 

Nano-delivery carriers offer a solution to the questions of TAC therapy. These carriers use self-assembly methods to improve molecular properties, employ biomimetic materials to mimic physiological processes, and improve therapeutic efficacy through engineered design.

Figure 7. 

Characterization of TAC-based self-assembling nanoplatforms and their performance. (a) Design strategy of endoTAC and its mechanistic role in AD therapy. (b) Intracellular distribution of nanoparticles in brain vascular endothelial cells. (c) Flow cytometric analysis of FITC-Aβ uptake in bEnd.3 cells following 24-h co-incubation with SV@NP. (d) Flow cytometry was used to analyze FITC-Aβ uptake in RAGE-overexpressing bEnd.3 cells after 24 h of co-culture with endoTAC. Reprinted with permission from Ref.^[5]. Copyright 2024 Wiley.

Figure 8. 

Design and experimental confirmation of TAC delivery via liposomes and polymer carriers. (a) Design of the liposome-based delivery platform and its mechanism of action in AD treatment. (b) Representative fluorescence images of coronal brain sections from C57 mice, showing Cy5-labeled PROTAC (red) and nuclear staining (blue). (c) Quantitative flow cytometric analysis of fluorescence intensity in TAU-EGFP-overexpressing N2a cells following PROTAC treatment at specified time points. (d) Western blot analysis was performed to assess the extent of tau protein degradation. Reprinted with permission from Ref.^[119]. Copyright 2024 Wiley. (e) Design of the polymer delivery carrier and its mechanism of action. (f) Representative in vivo bioluminescence imaging of tumor-bearing mice after treatment. (g) Cytotoxicity of cRGD-P/ARV, cRGD-P/DOX, and cRGD-P/ARV-DOX in GL261 cells after 24-h incubation was assessed using the MTT assay at concentrations ranging from 0 to 0.0625 μg·mL⁻¹. (h) Flow cytometric analysis of apoptosis in GL261 cells using Annexin V/PI double staining. Reprinted with permission from Ref.^[120]. Copyright 2022 Elsevier.

Figure 9. 

Characterization of TAC-based biomimetic carrier delivery platforms and their experimental confirmation. (a) In vivo and ex vivo fluorescence imaging of mice following tail vein injection of PBS, sc-FRONTAC^FUS, and FRONTAC^FUS. (b) Fluorescence imaging of brain tissue sections from mice administered Cy5-labeled dFUS-PS9C or Cy5-labeled FRONTAC^FUS via tail vein. (c) Immunoblot analysis of FUS level in hippocampal and cortical tissues from mice administered escalating doses of FRONTAC^FUS via tail vein injection. (d) Quantitative comparison of Western blot data analyzing differences in FUS degradation in hippocampal and cortical tissues following tail vein injection of NF control vs 10 mg·kg⁻¹ FRONTAC^FUS. Reprinted with permission from Ref.^[92]. Copyright 2025 Springer Nature. (e) Mechanism of action of the TAC biomimetic cell membrane delivery platform. (f) In vitro evaluation of the BBB penetration capacity of Cy5 LNP and M@Cy5 LNP using the Transwell assay. (g) In vivo distribution of free Cy5, Cy5 LNP, and M@Cy5 LNP measured at specified time points following tail vein injection in mice with orthotopic U251MG glioma. (h) Quantitative analysis of tumor bioluminescence signals in each treatment group. (i) Kaplan–Meier survival analysis for mice in each treatment group. Reprinted with permission from Ref.^[129]. Copyright 2025 Wiley.