Characterisation and tumour targeting of PEGylated polylysine dendrimers bearing doxorubicin via a pH labile linker
Abstract
Polylysine dendrimers have potential as biodegradable vectors for the delivery of cytotoxic drugs to solid tumours. Here, the cytotoxicity, drug release and tumour targeting properties of Generation 5 PEGylated polylysine dendrimers comprising an outer generation of l-lysine or succinimyldipropyldiamine (SPN) and containing doxorubicin (DOX) linked through an acid labile 4-(hydrazinosulfonyl) benzoic acid (HSBA) linker have been characterised. Less than 10% of the DOX load was released from LYS or SPN dendrimers in pH 7.4 buffer over 3 days. In contrast approximately 100% release was evident at pH 5. The DOX-conjugated dendrimers also retained similar cytotoxic properties to free DOX in in vitro cell culture studies (presumably as a result of in situ liberation of free DOX). The clearance patterns of the DOX conjugated SPN and all-lysine dendrimers were similar to the equivalent non-DOX conjugated systems, however the SPN dendrimers showed reduced metabolic lability and increased uptake into RES organs when compared to the equivalent all-lysine dendrimers. In vivo assessment of the DOX-conjugated, PEGylated polylysine dendrimers (both SPN and LYS constructs) in rats bearing Walker 256 tumours revealed higher uptake into tumour tissue when compared with control tissue such as muscle (~8 fold) and heart (~3 fold). The data suggest that polylysine dendrimers containing DOX conjugated via an acid labile HSBA linker may provide a mechanism to target the delivery of DOX to tumours.
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Polylysine dendrimers have the potential to be biodegradable carriers and deliver cytotoxic drugs to solid tumors.
“Polylysine dendrimers have the potential to be biodegradable carriers and deliver cytotoxic drugs to solid tumors.33”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [33]
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- Authors
- Kaminskas, L. M., Kelly, B. D., McLeod, V. M., Sberna, G., Owen, D. J., Boyd, B. J., & Porter, C. J. H.
- Affiliations
- Monash University (AU)
- Starpharma (Australia) (AU)
- Corresponding author
- Porter, Christopher J.H.
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 152
- Issue
- 2
- Pages
- 241-248
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2007359536
- Cited by
- 137
- References
- 41
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 15 · 2014: 10 · 2013: 12 · 2012: 7
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- PEGylation, doxorubicin, pH-responsive drug release, acid-labile linker, tumor targeting, biodegradable drug delivery, cytotoxicity, tissue distribution, macrophage uptake, controlled release
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Cell Survival, Doxorubicin, Humans, Hydrogen-Ion Concentration, Lysine, Male, Neoplasms, Polyethylene Glycols, Polylysine, Drug Delivery Systems, Rats, Sprague-Dawley, Cell Line, Tumor, Dendrimers, Rats
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