Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.

Haoran Zhu, Yijun Zhang, Yuhua Ning, Chaoyong Yang, Guihua Zhang, Zhi Zhu

Abstract readReview

In one paragraph

Review in Small methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Haoran ZhuThe MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

Yijun ZhangThe MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

Yuhua NingThe MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

Chaoyong YangThe MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.ORCID https://orcid.org/0000-0002-2374-5342

Guihua ZhangInstitute of Molecular Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.ORCID https://orcid.org/0009-0001-4359-756X

Zhi ZhuThe MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.ORCID https://orcid.org/0000-0002-3287-4920

Funding

Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China JYB2025XDXM507Fundamental Research Funds for the Central Universities 20720210001Fundamental Research Funds for the Central Universities 20720220005National Key R&D Program of China 2021YFA0909400National Natural Science Foundation of China 22293031National Natural Science Foundation of China 22325404National Natural Science Foundation of China 22521102

6 · The paper itself

Abstract

Targeted protein degradation (TPD) has redefined the therapeutic landscape by shifting the focus from merely inhibiting protein function to actively eliminating disease-causing proteins. However, the clinical translation of TPD agents remains hampered by their inherent physicochemical limitations, including poor solubility, membrane impermeability, and lack of tissue selectivity. Nanotechnology offers a strategic pathway to overcome these barriers. This review examines the convergence of TPD and nanotechnology, highlighting how diverse nanoplatforms-ranging from lipid and polymeric nanoparticles to inorganic carriers and biomimetic systems-can address fundamental delivery challenges. We discuss key design strategies such as physical encapsulation, chemical conjugation, and carrier-free self-assembly between nanocarrier-assisted TPD-where nanoparticles improve degrader pharmacokinetics-and nanostructure-integrated TPD-where the nanoscaffold directly participates in ternary complex formation, and explore how engineering the nano-bio interface enables precise control over cellular uptake, intracellular trafficking, and ternary complex formation. We also critically assess current translational hurdles, including manufacturing complexity, biosafety concerns, and tumor heterogeneity, while offering perspectives on how rational design and interdisciplinary collaboration can accelerate clinical adoption. By reimagining protein degraders as components of intelligent nano-systems, nano-TPD holds the potential to transform undruggable targets into actionable therapeutic opportunities.

Indexed as

NanotechnologyProteinsProteolysisAnimalsDrug Delivery SystemsHumansNanoparticlesProteinsdrug deliverynanocarriersprecision therapytargeted protein degradation

Identifiers

PMID42557840

DOI10.1002/smtd.70928

PMCPMC13555673

What OpenQuestion holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.