The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Smart Superstructures with Ultrahigh pH-Sensitivity for Targeting Acidic Tumor Microenvironment: Instantaneous Size Switching and Improved Tumor Penetration
Abstract
The currently low delivery efficiency and limited tumor penetration of nanoparticles remain two major challenges of cancer nanomedicine. Here, we report a class of pH-responsive nanoparticle superstructures with ultrasensitive size switching in the acidic tumor microenvironment for improved tumor penetration and effective in vivo drug delivery. The superstructures were constructed from amphiphilic polymer directed assembly of platinum-prodrug conjugated polyamidoamine (PAMAM) dendrimers, in which the amphiphilic polymer contains ionizable tertiary amine groups for rapid pH-responsiveness. These superstructures had an initial size of ∼80 nm at neutral pH (e.g., in blood circulation), but once deposited in the slightly acidic tumor microenvironment (pH ∼6.5-7.0), they underwent a dramatic and sharp size transition within a very narrow range of acidity (less than 0.1-0.2 pH units) and dissociated instantaneously into the dendrimer building blocks (less than 10 nm in diameter). This rapid size-switching feature not only can facilitate nanoparticle extravasation and accumulation via the enhanced permeability and retention effect but also allows faster nanoparticle diffusion and more efficient tumor penetration. We have further carried out comparative studies of pH-sensitive and insensitive nanostructures with similar size, surface charge, and chemical composition in both multicellular spheroids and poorly permeable BxPC-3 pancreatic tumor models, whose results demonstrate that the pH-triggered size switching is a viable strategy for improving drug penetration and therapeutic efficacy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Li and coworkers showed the size effect of pH-sensitive nanoparticles composed of dendrimer building blocks with better tumor penetration and their dissociation into smaller sizes in the tumor environment.245”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [245]
Citations
Cites
Nanocarriers as an emerging platform for cancer therapy
Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007) · Nature Nanotechnology · doi:10.1038/nnano.2007.387 · Cited by 8,710
Principles of nanoparticle design for overcoming biological barriers to drug delivery
Blanco, E., Shen, H., & Ferrari, M. (2015) · Nature Biotechnology · doi:10.1038/nbt.3330 · Cited by 7,002
Matsumura, Y., & Maeda, H. (1986) · PubMed · Cited by 6,781
Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy
Jain, R. K. (2005) · Science · doi:10.1126/science.1104819 · Cited by 5,527
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
Renal clearance of quantum dots
Soo Choi, H., Liu, W., Misra, P., Tanaka, E., Zimmer, J. P., Itty Ipe, B., Bawendi, M. G., & Frangioni, J. V. (2007) · Nature Biotechnology · doi:10.1038/nbt1340 · Cited by 4,476
Nanoparticle therapeutics: an emerging treatment modality for cancer
Davis, M. E., Chen, Z., & Shin, D. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2614 · Cited by 4,233
Delivering nanomedicine to solid tumors
Jain, R. K., & Stylianopoulos, T. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.139 · Cited by 3,265
Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size
Cabral, H., Matsumoto, Y., Mizuno, K., Chen, Q., Murakami, M., Kimura, M., Terada, Y., Kano, M. R., Miyazono, K., Uesaka, M., et al. (2011) · Nature Nanotechnology · doi:10.1038/nnano.2011.166 · Cited by 2,429
Spheroid-based drug screen: Considerations and practical approach
Friedrich, J., Seidel, C., Ebner, R., & Kunz-Schughart, L. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.226 · Cited by 1,742
Research works printed but not linked: 1
- Matsumura Y., 1986, Cancer Res., 46, 6387
Cited by
Sorted by citations
Engineering precision nanoparticles for drug delivery
Mitchell, M. J., Billingsley, M. M., Haley, R. M., Wechsler, M. E., Peppas, N. A., & Langer, R. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0090-8 · Cited by 7,933
Polymer–drug conjugate therapeutics: advances, insights and prospects
Ekladious, I., Colson, Y. L., & Grinstaff, M. W. (2018) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0005-0 · Cited by 882
Stimuli-responsive nanocarriers for drug delivery, tumor imaging, therapy and theranostics
Mi, P. (2020) · Theranostics · doi:10.7150/thno.38069 · Cited by 874
Enzyme-activatable polymer–drug conjugate augments tumour penetration and treatment efficacy
Zhou, Q., Shao, S., Wang, J., Xu, C., Xiang, J., Piao, Y., Zhou, Z., Yu, Q., Tang, J., Liu, X., et al. (2019) · Nature Nanotechnology · doi:10.1038/s41565-019-0485-z · Cited by 831
Self-citationDendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy
Palmerston Mendes, L., Pan, J., & Torchilin, V. (2017) · Molecules · doi:10.3390/molecules22091401 · Cited by 701
Metadata
- Authors
- Li, H.-J., Du, J.-Z., Liu, J., Du, X.-J., Shen, S., Zhu, Y.-H., Wang, X., Ye, X., Nie, S., & Wang, J.
- Affiliations
- Georgia Institute of Technology (US)
- University of Science and Technology of China (CN)
- Hefei National Laboratory for Physical Sciences at the Microscale, Hefei, Anhui 230027, China
- Corresponding author
- Du, Jin-Zhi
- Nie, Shuming
- Wang, Jun
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-06-03
- Volume
- 10
- Issue
- 7
- Pages
- 6753-6761
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2409932367
- Cited by
- 537
- References
- 46
- Citations by year
- 2026: 14 · 2025: 32 · 2024: 31 · 2023: 41 · 2022: 58 · 2021: 69 · 2020: 80 · 2019: 73 · 2018: 76 · 2017: 52 · 2016: 10
- FWCI
- 28.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA163256)
- Ministry of Science and Technology of the People's Republic of China (2012CB932500, 2013CB933900, 2015CB932100)
- National Natural Science Foundation of China (51390482)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- pH-responsive nanoparticles, tumor acidosis, tumor penetration, PAMAM dendrimers, platinum prodrug, tertiary amines, enhanced permeability and retention effect, nanoparticle extravasation, pancreatic cancer, tumor spheroids, drug delivery
- MeSH terms
- Humans, Hydrogen-Ion Concentration, Neoplasms, Drug Delivery Systems, Cell Line, Tumor, Dendrimers, Nanoparticles, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
