Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention
Abstract
We studied the molecular mechanism of greater efficacy of paclitaxel-loaded nanoparticles (Tx-NPs) following conjugation to transferrin (Tf) ligand in breast cancer cell line. NPs were formulated using biodegradable polymer, poly(lactic-co-glycolide) (PLGA), with encapsulated Tx and conjugated to Tf ligand via an epoxy linker. Tf-conjugated NPs demonstrated greater and sustained antiproliferative activity of the drug in dose- and time-dependent studies compared to that with drug in solution or unconjugated NPs in MCF-7 and MCF-7/Adr cells. The mechanism of greater antiproliferative activity of the drug with conjugated NPs was determined to be due to their greater cellular uptake and reduced exocytosis compared to that of unconjugated NPs, thus leading to higher and sustained intracellular drug levels. The increase in antiproliferative activity of the drug with incubation time in MCF-7/Adr cells with Tf-conjugated NPs suggests that the drug resistance can be overcome by sustaining intracellular drug retention. The intracellular disposition characteristics of Tf-conjugated NPs following their cellular uptake via Tf receptors could have been different from that of unconjugated NPs via nonspecific endocytic pathway, thus influencing the NP uptake, their intracellular retention, and hence the therapeutic efficacy of the encapsulated drug.
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A variety of studies confirmed an improved anti-cancer drug uptake upon conjugation to a TfR monoclonal antibody.
“In fact, a variety of studies confirmed an improved anti-cancer drug uptake upon conjugation to a TfR monoclonal antibody [101,102,103].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [103]
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Self-citation
- Authors
- Sahoo, S. K., & Labhasetwar, V.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Labhasetwar, Vinod
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2005-06-21
- Volume
- 2
- Issue
- 5
- Pages
- 373-383
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2074772243
- Cited by
- 340
- References
- 36
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 12 · 2020: 15 · 2019: 25 · 2018: 15 · 2017: 18 · 2016: 24 · 2015: 19 · 2014: 21 · 2013: 28 · 2012: 26
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- paclitaxel, PLGA nanoparticles, intracellular drug retention, breast cancer, MCF-7 cells, MCF-7/ADR cells, drug resistance, transferrin receptor, cellular uptake, exocytosis, antiproliferative activity, targeted drug delivery
- MeSH terms
- Humans, Magnetic Resonance Spectroscopy, Temperature, Transferrin, Molecular Structure, Intracellular Space, Taxoids, Cell Line, Tumor, Microscopy, Electron, Transmission, Cell Proliferation, Nanostructures
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