Functionalized Gold Nanoparticles for Stable Uptake and Radiosensitization
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Solution Overview
Problem
Existing treatments for prostate cancer, such as radiotherapy, face challenges with nanoparticle stability, aggregation, and cellular uptake, leading to reduced efficacy and harmful side effects, particularly due to the use of high concentrations of gold nanoparticles and stabilizers like PEG, which hinder internalization.
Innovation Solution
Development of nanoparticles functionalized with a stabilizing agent and a targeting agent, such as thiol-terminated polyethylene glycol and a pepducin, to enhance stability, cellular uptake, and radiosensitization, while minimizing cytotoxicity and side effects, using a core material like gold with a mean hydrodynamic diameter of 5 to 50 nm and a molar ratio of stabilizing agent to targeting agent between 1:2 to 1:5.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high concentrations of gold nanoparticles are used to improve radiosensitization efficacy, then treatment efficacy is improved, but cost and toxicity increase significantly
Solution Approach 1:
The patent changes the concentration parameter of gold nanoparticles from high (1 wt%) to low (0.01-0.1 wt%), achieving comparable radiosensitization efficacy through improved stability and cellular uptake rather than increased concentration
Solution Approach 2:
The patent creates a composite nanoparticle system combining gold core with PEG stabilizing agent and targeting agent (peptide or antibody), where the composite structure provides both stability for low concentration use and enhanced cellular uptake for improved efficacy
2Stability of the object's composition
If PEG is used as a stabilizer to prevent nanoparticle aggregation, then stability is improved, but cellular internalization is severely hindered
Solution Approach 1:
The patent segments the nanoparticle surface into distinct functional zones: PEG molecules provide steric stabilization on the outer surface preventing aggregation, while targeting agents (peptides or antibodies) are positioned to mediate cellular recognition and uptake, allowing both stability and internalization functions to operate simultaneously
Solution Approach 2:
The patent applies different properties to different parts of the nanoparticle surface: PEG provides hydrophilic stabilization on the exterior, while localized regions contain targeting agents with specific binding affinity for cellular receptors, creating local functional zones that resolve the stability-uptake contradiction
3Reliability
If radiotherapy is used to treat prostate cancer to achieve cure, then treatment efficacy is improved, but damage to surrounding healthy tissue occurs in roughly 50% of men
Solution Approach 1:
The patent introduces functionalized gold nanoparticles as an intermediary between radiation and cancer cells. The nanoparticles accumulate selectively in tumor tissue through passive EPR effect and active targeting, then convert radiation energy locally through photoelectric effect and Auger electron emission, mediating the therapeutic effect while protecting surrounding healthy tissue
Solution Approach 2:
The patent changes the radiation dose parameter by using nanoparticles to enhance the biological effectiveness of lower radiation doses. The high-Z gold atoms increase photon absorption and local energy deposition, allowing effective treatment at reduced doses that minimize damage to healthy tissues
4Ease of manufacture
If as-synthesised nanoparticles are used to treat cancer, then treatment simplicity is maintained, but nanoparticles aggregate at physiological conditions significantly reducing efficacy
Solution Approach 1:
The patent performs preliminary stabilization of nanoparticles during the synthesis process itself by adding PEG and targeting agents to the nanoparticle formation reaction. This preliminary functionalization ensures colloidal stability is established before the nanoparticles encounter physiological conditions, preventing aggregation during storage and administration
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The nanoparticles provide improved stability, increased cellular uptake, and enhanced radiosensitization, allowing for lower radiation doses and reduced damage to healthy cells, thereby increasing treatment efficacy and reducing side effects.
Implementation Method 1
the stabilising agent and targeting agent are added respectively at a molar ratio of from about 1:2 to about 1:5
Implementation Method 2
polyethylene glycol (PEG) has been used as a stabiliser
Implementation Method 3
the targeting agent comprises a peptide chain having between 3 and 15 amino acid residues or between 20 to 50 amino acid residues
Implementation Method 4
the core comprises a chemical element having an atomic number of from about 44 to about 83
Implementation Method 5
increased radiosensitisation (including at clinical energies)
Data Source
Figure 1A~1D
Figure 2A~2H
Figure 3A~3F
AI summary
The present invention relates to functionalised nanoparticles. The present invention also relates to compositions comprising the functionalised nanoparticles, kits, processes for preparing nanoparticles, methods of treating cancer (including prostate cancer), imaging methods, diagnostic methods, methods for killing or attenuating the growth of a cancer cell in vitro, nanoparticles and compositions for use in the treatment of cancer or diagnosis, and a novel pepducin.