The DOI matches its Crossref record; 97 of the 99 references it cites were found in a registry or an index.
Enzyme-responsive nanoparticles for drug release and diagnostics
Abstract
Enzymes are key components of the bionanotechnology toolbox that possess exceptional biorecognition capabilities and outstanding catalytic properties. When combined with the unique physical properties of nanomaterials, the resulting enzyme-responsive nanoparticles can be designed to perform functions efficiently and with high specificity for the triggering stimulus. This powerful concept has been successfully applied to the fabrication of drug delivery schemes where the tissue of interest is targeted via release of cargo triggered by the biocatalytic action of an enzyme. Moreover, the chemical transformation of the carrier by the enzyme can also generate therapeutic molecules, therefore paving the way to design multimodal nanomedicines with synergistic effects. Dysregulation of enzymatic activity has been observed in a number of severe pathological conditions, and this observation is useful not only to program drug delivery in vivo but also to fabricate ultrasensitive sensors for diagnosing these diseases. In this review, several enzyme-responsive nanomaterials such as polymer-based nanoparticles, liposomes, gold nanoparticles and quantum dots are introduced, and the modulation of their physicochemical properties by enzymatic activity emphasized. When known, toxicological issues related to the utilization nanomaterials are highlighted. Key examples of enzyme-responsive nanomaterials for drug delivery and diagnostics are presented, classified by the type of effector biomolecule, including hydrolases such as proteases, lipases and glycosidases, and oxidoreductases.
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“The most advanced of these are lipid-based NPs (liposomes and SLNs), which have proven biocompatibility and the ability to carry both hydrophilic and hydrophobic drugs. However, their clinical application has been hindered by rapid clearance via the reticuloendothelial system (RES) and stability issues, resulting in some trial failures [9, 100].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [100]
In the citing paper
“Polymeric NPs offer the advantages of controlled drug release and modifiable surface properties that enhance targeting and circulation time. However, concerns about polymer degradation, toxicity, and inconsistent BBB penetration limit their clinical application, despite some encouraging preclinical data [100, 155].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [100]
In the citing paper
“While some trials have demonstrated the safety and feasibility of these therapies, many face challenges relating to therapeutic efficacy, pharmacokinetics, and long-term safety. This has led to the discontinuation of some trials or slow progression.”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [100]
In the citing paper
“Despite promising preclinical results, the clinical translation of nanomedicine-based AD therapies remains in its early stages. Only a few NP formulations have entered clinical trials, with the main focus being on improving drug delivery across the BBB and targeting Aβ or tau pathology.”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [100]
In the citing paper
“The development of enzyme-responsive nanoparticles for targeted therapy of tumor microenvironment is another effective strategy for nanoparticle intelligence which could release the payload into the desired target.143”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [143]
Citations
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Flagged first, then by citations
2 of the 99 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Kurtzberg, 1988, A phase II study of polyethylene glycol (PEG) conjugated l-asparaginase in patients with refractory acute leukaemias, Proc. Am. Assoc. Cancer Res., 29, 213
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Sorted by citations
Analysis of nanoparticle delivery to tumours
Wilhelm, S., Tavares, A. J., Dai, Q., Ohta, S., Audet, J., Dvorak, H. F., & Chan, W. C. W. (2016) · Nature Reviews Materials · doi:10.1038/natrevmats.2016.14 · Cited by 5,218
Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00346 · Cited by 3,070
Engineered Nanoparticles for Drug Delivery in Cancer Therapy
Sun, T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M., & Xia, Y. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201403036 · Cited by 2,164
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Kamaly, N., Xiao, Z., Valencia, P. M., Radovic‐Moreno, A. F., & Farokhzad, O. C. (2012) · Chemical Society Reviews · doi:10.1039/c2cs15344k · Cited by 1,774
Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems
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Metadata
- Authors
- de la Rica, R., Aili, D., & Stevens, M. M.
- Affiliations
- Nanyang Technological University (SG)
- Imperial College London (GB)
- Corresponding author
- Stevens, Molly M.
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 64
- Issue
- 11
- Pages
- 967-978
- ISSN
- 0169-409X (ISSN-L)
- OpenAlex
- W2162750459
- Cited by
- 765
- References
- 99
- Citations by year
- 2026: 42 · 2025: 57 · 2024: 52 · 2023: 48 · 2022: 60 · 2021: 56 · 2020: 65 · 2019: 68 · 2018: 59 · 2017: 64 · 2016: 53 · 2015: 62 · 2014: 45 · 2013: 24 · 2012: 10
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (acceptedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Funders
- Engineering and Physical Sciences Research Council (EP/J013331/1)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Keywords
- enzyme-responsive nanoparticles, stimuli-responsive drug delivery, enzyme-responsive drug release, nanomedicine, ultrasensitive biosensor, polymeric nanoparticles, liposomes, gold nanoparticles, quantum dots, proteolytic enzymes, lipase, glycoside hydrolases, oxidative enzymes, nanomaterial toxicity
- MeSH terms
- Diagnostic Imaging, Pharmaceutical Preparations, Hydrolases, Drug Delivery Systems, Nanoparticles
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