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Updated: Aug 13, 2026
Viral Nanoparticles for In vivo Tumor Imaging
Published on: November 16, 2012
Biodegradable nanoparticles for direct or two-step tumor immunotargeting
Leila Nobs1, Franz Buchegger, Robert Gurny
1Department of Pharmaceutical Technology and Biopharmaceutics, School of Pharmaceutical Sciences, Ecole de Pharmacie Genève-Lausanne, University of Geneva, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland.
Abstract:
In this study, selective cancer cell targeting of biodegradable poly(lactic acid) (PLA) nanoparticles (NPs) has been investigated in vitro. SKOV-3 (HER2 positive) ovarian cancer and Daudi (CD20 positive) lymphoma cell targeting was mediated by anti-HER2 (trastuzumab, Herceptin) and anti-CD20 (rituximab, Mabthera) monoclonal antibodies (mAbs), respectively. The mAb against nonexpressed antigen serving on each cell as isotype matched irrelevant control. Two different targeting approaches have been studied, a direct method using antibody-labeled NPs (mAb-NPs) and a pretargeting method using the avidin-biotin technology. For the direct protocol, fluorescent PLA-NPs were prepared including 10% 1-pyrenebutanol (PB)-labeled PLA in the NP-preparation (PB-NP). Thiol groups were covalently bound to the PB-NP, and the resulting thiolated PB-NP were coupled with the two mAbs using a bifunctional cross-linker. The effective targeting of cells by mAb-PB-NP was shown by flow cytometry analysis. Clearly anti-HER2-PB-NP specifically bound to the SKOV-3 cells and not to the Daudi cells, while anti-CD20-PB-NPs bound to Daudi cells but not to SKOV-3 cells. Specific mAb-PB-NP binding to tumor cells produced a mean 10-fold or higher signal increase compared to irrelevant IgG-PB-NPs. For the pretargeting protocol, plain PLA-NPs were also thiolated and NeutrAvidin-Rhodamine Red-X (NAR) coupled to the functionalized PLA-NPs with sulfo-MBS. The two-step method was evaluated in vitro by incubating SKOV-3 cells first with biotinylated mAbs followed by NAR-NPs. The relative fluorescence associated to the specific binding of NPs produced a 6-fold increase in flow cytometry signal compared to nonspecific binding. In conclusion, these experiments have shown that NPs covalently coupled with antibodies or NAR can specifically and efficiently bind to cancer cells in both a pretargeting and a direct approach, suggesting that functionalized NPs may be a useful drug carrier for tumor targeting.
Insights
Biodegradable poly(lactic acid) nanoparticles (NPs) functionalized with antibodies selectively targeted HER2-positive ovarian and CD20-positive lymphoma cancer cells in vitro. Both direct and pretargeting methods demonstrated efficient and specific cancer cell binding, indicating potential as drug carriers.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Oncology
Background:
- Targeted cancer therapy aims to deliver drugs specifically to tumor cells, minimizing off-target effects.
- Biodegradable nanoparticles offer a promising platform for drug delivery due to their biocompatibility and tunable properties.
- Antibody-functionalized nanoparticles can enhance specificity by targeting cancer-associated antigens.
Purpose of the Study:
- To investigate the in vitro targeting efficiency of biodegradable poly(lactic acid) (PLA) nanoparticles (NPs) for selective cancer cell delivery.
- To compare the efficacy of direct antibody-labeling versus a pretargeting approach for NP-mediated cancer cell targeting.
- To evaluate the potential of functionalized NPs as drug carriers for tumor-specific delivery.
Main Methods:
- Preparation of fluorescent PLA nanoparticles (PB-NPs) and functionalization with thiol groups.
- Direct targeting: Covalent coupling of anti-HER2 or anti-CD20 monoclonal antibodies (mAbs) to thiolated PB-NPs.
- Pretargeting: Incubation of cells with biotinylated mAbs followed by NeutrAvidin-Rhodamine Red-X (NAR)-coupled NPs.
- Flow cytometry analysis to assess specific binding of antibody-conjugated NPs to SKOV-3 (HER2+) and Daudi (CD20+) cancer cells.
Main Results:
- Anti-HER2-PB-NPs specifically bound to SKOV-3 cells, and anti-CD20-PB-NPs specifically bound to Daudi cells, with a mean signal increase of 10-fold compared to irrelevant IgG-NPs.
- The pretargeting method showed a 6-fold increase in specific NP binding signal compared to nonspecific binding.
- Both direct and pretargeting approaches demonstrated efficient and specific binding of functionalized NPs to their respective target cancer cells.
Conclusions:
- Functionalized PLA nanoparticles can be effectively targeted to specific cancer cells in vitro using both direct antibody conjugation and pretargeting strategies.
- The developed antibody-coupled or NeutrAvidin-coupled NPs show promise as a drug delivery system for targeted cancer therapy.
- This study highlights the potential of nanotechnology in developing novel and efficient cancer treatment modalities.
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