In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications
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A Comprehensive Procedure to Evaluate the In Vivo Performance of Cancer Nanomedicines
Published on: March 4, 2017
Yong Woo Cho1, Soo Ah Park, Tae Hee Han
1Department of Chemical Engineering, Hanyang University, Ansan 426 791, Republic of Korea.
Abstract:
The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to evaluate various self-assembled nanoparticles as candidates to shuttle radionuclide and/or drugs into tumors and to investigate the mechanisms underlying the tumor targeting with self-assembled nanoparticles. By combining different hydrophobic moieties and hydrophilic polymer backbones, various self-assembled nanoparticles were prepared, and their in vivo distributions in tumor-bearing mice were studied by radionuclide imaging. One type of nanoparticles (fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles) exhibited highly selective tumoral localization. Scintigraphic images obtained 1 day after the intravenous injection of FGC nanoparticles clearly delineated the tumor against adjacent tissues. The mechanisms underlying the tumor targeting with self-assembled nanoparticles were investigated in terms of the physicochemical properties of nanoparticles and tumor microenvironments. FGC nanoparticles were preferentially localized in perivascular regions, implying their extravasation to tumors through the hyperpermeable tumor vasculature. The magnitude and pattern of tumoral distribution of self-assembled nanoparticles were influenced by several key factors--(i) in vivo colloidal stability: nanoparticles should maintain their intact nanostructures in vivo for a long period of time, (ii) particle size, (iii) intracellular uptake of nanoparticle: fast cellular uptake greatly facilitates the tumor targeting, (iv) tumor angiogenesis: pathological angiogenesis permits access of nanoparticles to tumors. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis, so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.
Insights
Researchers developed self-assembled nanoparticles for targeted cancer delivery. Fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles showed selective tumor accumulation, paving the way for improved cancer diagnosis and therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Developing selective delivery systems for cancer diagnosis and chemotherapy is crucial in anticancer research.
- Self-assembled nanoparticles offer potential as carriers for radionuclides and drugs into tumors.
- Understanding tumor targeting mechanisms is key to optimizing nanoparticle-based therapies.
Purpose of the Study:
- To evaluate self-assembled nanoparticles for tumor targeting of radionuclides and/or drugs.
- To investigate the mechanisms responsible for tumor targeting by these nanoparticles.
- To identify key factors influencing nanoparticle distribution within tumors.
Main Methods:
- Synthesized various self-assembled nanoparticles by combining hydrophobic moieties and hydrophilic polymer backbones.
- Studied in vivo distribution of nanoparticles in tumor-bearing mice using radionuclide imaging.
- Analyzed physicochemical properties of nanoparticles and tumor microenvironments to understand targeting mechanisms.
Main Results:
- Fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles demonstrated highly selective tumoral localization.
- Scintigraphic imaging confirmed clear delineation of tumors from adjacent tissues 1 day post-injection of FGC nanoparticles.
- FGC nanoparticles localized in perivascular regions, suggesting extravasation via hyperpermeable tumor vasculature.
Conclusions:
- In vivo colloidal stability, particle size, intracellular uptake, and tumor angiogenesis significantly influence nanoparticle tumor distribution.
- This research provides insights for engineering nanoparticles for enhanced cancer therapy and diagnosis.
- Optimized nanoparticles can deliver therapeutic agents and imaging probes at high local concentrations for improved cancer treatment.
