ArticleBiomacromolecules2009
Intracellular trafficking and subcellular distribution of a large array of HPMA copolymers.
Article in Biomacromolecules, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- Biocompatible Gadolinium Oxide Nanoparticles Incorporated Doxorubicin Enables Magnetic Resonance and Photoacoustic Dual Imaging for Cancer Theranostics.Nanomaterials (Basel, Switzerland) · 2026Article
- Hydrophilic biomaterials: From crosslinked and self-assembled hydrogels to polymer-drug conjugates and drug-free macromolecular therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Advances in Multiple Stimuli-Responsive Drug-Delivery Systems for Cancer Therapy.International journal of nanomedicine · 2021Review
- Intratumoral Distribution and pH-Dependent Drug Release of High Molecular Weight HPMA Copolymer Drug Conjugates Strongly Depend on Specific Tumor Substructure and Microenvironment.International journal of molecular sciences · 2020Article
- Polymer nanomedicines.Advanced drug delivery reviews · 2020Review
- Design of smart HPMA copolymer-based nanomedicines.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- Anticancer nanoparticulate polymer-drug conjugate.Bioengineering & translational medicine · 2016Review
- Macromolecular therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2014Review
- Polymer-drug conjugates: origins, progress to date and future directions.Advanced drug delivery reviews · 2013Review
- An analysis of interactions between fluorescently-tagged mutant and wild-type SOD1 in intracellular inclusions.PloS one · 2013Article
- Superoxide dismutase 1 encoding mutations linked to ALS adopts a spectrum of misfolded states.Molecular neurodegeneration · 2011Article
- PEG-poly(amino acid) block copolymer micelles for tunable drug release.Pharmaceutical research · 2010Article
- Endocytic uptake of a large array of HPMA copolymers: Elucidation into the dependence on the physicochemical characteristics.Journal of controlled release : official journal of the Controlled Release Society · 2010Article
- HPMA copolymers: origins, early developments, present, and future.Advanced drug delivery reviews · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The basic physicochemical properties that determine the distribution and fate of synthetic macromolecules in living cells were characterized using fluorescently labeled HPMA (N-(2-hydroxypropyl)methacrylamide) copolymers. Twelve different classes of water-soluble copolymers were created by incorporating eight different functionalized comonomers. These comonomers possessed functional groups with positive or negative charges or contained short hydrophobic peptides. The copolymers were fractionated to create parallel "ladders" consisting of 10 fractions of narrow polydispersity with molecular weights ranging from 10 to 200 kDa. The intracellular distributions were characterized for copolymer solutions microinjected into the cytoplasm of cultured ovarian carcinoma cells. Even the highest molecular weight HPMA copolymers were shown to quickly and evenly diffuse throughout the cytoplasm and remain excluded from membrane-bound organelles, regardless of composition. The exceptions were the strongly cationic copolymers, which demonstrated a pronounced localization to microtubules. For all copolymers, nuclear entry was consistent with passive transport through the nuclear pore complex (NPC). Nuclear uptake was shown to be largely dictated by the molecular weight of the copolymers, however, detailed kinetic analyses showed that nuclear import rates were moderately, but significantly, affected by differences in comonomer composition. HPMA copolymers containing amide-terminated phenylalanine-glycine (FG) sequences, analogous to those found in the NPC channel protein, demonstrated a potential to regulate import to the nuclear compartment. Kinetic analyses showed that 15 kDa copolymers containing GGFG, but not those containing GGLFG, peptide pendant groups altered the size-exclusion characteristics of NPC-mediated nuclear import.
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Registered trials
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.