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Updated: Jan 6, 2026
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
In situ real-time tracing of hierarchical targeting nanostructures in drug resistant tumors using diffuse
Qianqian Guo1, Yangyun Wang2, Limin Zhang3
1Key Laboratory of Functional Polymer Materials of Ministry of Education , Institute of Polymer Chemistry , College of Chemistry , Nankai University , Tianjin 300071 , China .
Abstract:
Nanoparticles that respond to specific endogenous or exogenous stimuli in tumor tissues are actively being developed to address multidrug resistance owing to multiple advantages, including a prolonged circulation time, enhanced permeability and retention effect, and superior cellular uptake. Although some exciting results have been obtained, existing nanoparticles have limited routes to overcome the drug resistance of tumor cells; this limitation results in a failure to ablate resistant tumors via intravenous administration. To resolve this dilemma, we developed a smart theranostic nanoplatform with programmable particle size, activatable target ligands and in vivo multimodal imaging. This nanoplatform, which includes stealth zwitterionic coating, was shown to be quickly trapped in tumor tissue from the blood circulation within 5 min. Subsequently, the targeting moieties were activated in response to the acidic tumor microenvironment by triggering the zwitterionic shell detachment, driving the peeled nanoparticles to penetrate into tumor cells. These smart nanoparticles completely inhibited drug-resistant tumor growth and did not cause any damage to normal organ tissues in live animals. The designed nanoplatforms simultaneously acted as a nanoprobe for fluorescence imaging. Moreover, we also used noninvasive pharmacokinetic diffuse fluorescence tomography (DFT) to dynamically monitor and in situ real-time trace the nanoplatforms' behavior throughout the entire tumor in live animals. The nanoplatforms enabled rapid drug accumulation and deep penetration throughout the entire tumor. The rate of drug accumulation after the administration of nanoplatforms was five-fold higher compared with that after the administration of the free drug, which resulted in increased drug delivery efficiency and improved antitumor efficacy. Collectively, this hierarchical vehicle design provides promising insights for the development of theragnosis for multidrug resistant tumors.
Insights
Researchers developed smart nanoparticles that overcome tumor drug resistance by changing size and targeting cancer cells in acidic environments. This theranostic nanoplatform enhances drug delivery and inhibits tumor growth without harming healthy tissues.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Multidrug resistance in tumors limits conventional cancer therapy effectiveness.
- Existing nanoparticles show promise but struggle to overcome tumor cell drug resistance via intravenous administration.
- Developing stimuli-responsive nanocarriers is crucial for targeted cancer treatment.
Purpose of the Study:
- To design a smart theranostic nanoplatform capable of overcoming multidrug resistance in tumors.
- To engineer nanoparticles with programmable size, activatable targeting ligands, and in vivo imaging capabilities.
- To investigate the nanoplatform's efficacy in inhibiting drug-resistant tumor growth and its pharmacokinetic behavior.
Main Methods:
- Development of a stealth zwitterionic-coated nanoplatform with a pH-sensitive shell.
- In vivo administration and tracking of nanoparticles using fluorescence imaging and diffuse fluorescence tomography (DFT).
- Assessment of nanoparticle accumulation, tumor penetration, and therapeutic efficacy in inhibiting drug-resistant tumors.
Main Results:
- The nanoplatform rapidly accumulated in tumor tissue within 5 minutes and penetrated tumor cells upon activation in the acidic tumor microenvironment.
- Smart nanoparticles completely inhibited drug-resistant tumor growth in vivo without causing damage to normal tissues.
- The nanoplatform demonstrated enhanced drug accumulation (five-fold higher than free drug) and deep tumor penetration, leading to improved antitumor efficacy.
Conclusions:
- The designed theranostic nanoplatform effectively overcomes multidrug resistance by responding to the tumor microenvironment.
- This hierarchical vehicle design offers a promising strategy for theranosis in multidrug-resistant tumors.
- The nanoplatform's ability for real-time in vivo tracking and targeted drug delivery enhances therapeutic outcomes.
