Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer
Open accessAbstract
Purpose A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease.Methods and materials The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated in vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration.Results Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of -8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration.Conclusions We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.
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Under sink conditions, paclitaxel was slowly released from Genexol PM micelle with 65% released at 24 hours and 95% at 48 hours.
“Under sink conditions, paclitaxel was slowly released from the micelle with 65% released at 24 hours and 95% released at 48 hours [110].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [110]
The Results, under “Characterization of Genexol-PM” (page not provided), report approximately 65% paclitaxel release at 24 hours and 95% at 48 hours; the Discussion describes the release as slow. The Methods describe a dialysis assay but do not state that it was conducted under sink conditions, so that qualifier is not supported by our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredGenexol PM, a clinically approved paclitaxel polymeric micelle, uses mPEG-b-PDLLA to solubilize paclitaxel.
“The clinically approved polymeric micelle formulation of paclitaxel Genexol® PM formulation exploits mPEG-b-PDLLA to solubilize paclitaxel and is discussed in greater detail in Section 5.3 [110].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [110]
Micelle systems prepared using PCL-b-PEG-b-PCL displayed high loading up to 28% of paclitaxel.
“For instance, micelle systems prepared using PCL-b-PEG-b-PCL displayed high loading up to 28% of paclitaxel [83].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [83]
The Introduction describes Genexol-PM as an mPEG-PDLLA paclitaxel micelle, and Methods and Materials > Materials reports 115 mg of paclitaxel per gram of Genexol-PM. Searches for PCL-b-PEG-b-PCL and 28% loading found no passage about that formulation or its loading capacity. The different composition reported for Genexol-PM does not rule out the claim about other micelles. (LLM, conf=0.76)
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- Authors
- Werner, M. E., Cummings, N. D., Sethi, M., Wang, E. C., Sukumar, R., Moore, D. T., & Wang, A. Z.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Wang, Andrew Z.
- Venue
- International Journal of Radiation Oncology*Biology*Physics
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 86
- Issue
- 3
- Pages
- 463-468
- ISSN
- 0360-3016 (ISSN-L)
- PMC
- PMC3750707
- OpenAlex
- W2169498622
- Cited by
- 267
- References
- 22
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 21 · 2023: 31 · 2022: 24 · 2021: 18 · 2020: 23 · 2019: 18 · 2018: 23 · 2017: 19 · 2016: 22 · 2015: 12 · 2014: 8 · 2013: 4 · 2012: 1
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Journal of Radiation Oncology*Biology*Physics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u54ca151652-05, 2k12ca120780-16)
- National Cancer Institute (5-K12-CA120780-01-05, U54‐CA151652, 1-U54-CA151652-01, K12-CA120780, R01CA178748)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- paclitaxel, nanoparticle drug delivery, radiosensitizers, non-small cell lung cancer, chemoradiotherapy, controlled drug release, nanoparticle size and surface charge, taxol comparison
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Carcinoma, Non-Small-Cell Lung, Lung, Lung Neoplasms, Mice, Nude, Polymers, Radiation-Sensitizing Agents, Paclitaxel, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Mice, Nanoparticles, Chemoradiotherapy
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