ATP-Functionalized Metallic Nanoclusters for Dormant Cell Eradication
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Solution Overview
Problem
Bacteria develop resistance to antibiotics, forming biofilms that protect dormant phenotypes (VBNC and persisters) making infections difficult to treat, and there is a lack of effective strategies to combat antibiotic-resistant infections and cancer.
Innovation Solution
Metallic nanoclusters less than 10 nm in size, conjugated to adenosine triphosphate (ATP) or analogues, are used to eradicate cells in a growth arrest phase, induce endoplasmic reticulum stress, and inhibit purinergic P2X7 receptors and FtsH protease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibiotics are used to treat bacterial infections, then bacterial growth is inhibited, but bacteria develop resistance and form protective biofilms
Solution Approach 1:
The patent introduces metallic nanoclusters conjugated to ATP or analogues as an intermediary substance that penetrates bacterial cells and disrupts essential processes. These nanoclusters act as a mediator between the external environment and internal bacterial machinery, specifically targeting ATP-dependent processes to collapse bacterial energy metabolism and protein synthesis, thereby eliminating resistance mechanisms while maintaining antibiotic effectiveness.
Solution Approach 2:
The patent changes the fundamental parameter of energy metabolism by introducing exogenous ATP or analogues that alter the intracellular energy state. By manipulating the ATP/ADP ratio and energy availability, the nanoclusters force bacterial cells into a state of metabolic collapse, preventing the expression of resistance genes and disabling protective biofilm formation mechanisms.
2Productivity
If antibiotics are used to treat biofilm infections, then planktonic bacteria are killed, but dormant phenotypes (VBNC and persisters) survive
Solution Approach 1:
The patent applies preliminary action by using nanoclusters conjugated to ATP analogues that specifically target and disrupt the energy metabolism of dormant phenotypes before they can establish protective biofilms or escape the immune system. The ATP analogues pre-condition the bacterial cells, making them susceptible to subsequent antibiotic treatment and preventing their emergence as resistant persisters.
Solution Approach 2:
Instead of using antibiotics to kill active bacteria and hoping dormant cells die by default, the patent inverts the approach by using ATP-conjugated nanoclusters to actively target and destroy dormant phenotypes through metabolic collapse. This inversion of the traditional antibiotic mechanism directly addresses the survival of persisters and VBNC cells that conventional antibiotics miss.
3Adaptability or versatility
If new antibiotics are developed to combat resistance, then treatment options increase, but development pipeline is slow and economic incentive is insufficient
Solution Approach 1:
The patent applies universality by designing metallic nanoclusters conjugated to ATP or analogues that can target multiple bacterial processes simultaneously - energy metabolism, protein synthesis, and biofilm formation. This multi-functional approach eliminates the need for multiple separate antibiotics and creates a single versatile agent that addresses current and future resistance mechanisms, thereby accelerating the development pipeline.
Solution Approach 2:
The patent uses composite materials by combining metallic nanoclusters (providing cellular penetration and metabolic disruption) with ATP or analogues (providing targeted energy metabolism collapse). This composite approach creates a synergistic therapeutic agent that overcomes resistance mechanisms more effectively than conventional single-mechanism antibiotics, increasing treatment options and accelerating drug discovery.
4Reliability
If ATP-conjugated metallic nanoclusters are used to treat infections, then dormant bacteria are eradicated, but the mechanism of action is complex
Solution Approach 1:
The patent applies segmentation by dividing the mechanism of action into distinct functional components: (1) nanocluster penetration of the cell membrane, (2) ATP analogue binding to bacterial ATP-dependent processes, (3) metabolic collapse and protein synthesis disruption, and (4) cell death. This segmentation simplifies the overall complex mechanism into manageable steps that can be targeted and optimized independently.
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 nanoclusters effectively target and eliminate antibiotic-resistant bacteria and cancer cells, enhancing the efficacy of antibiotic treatment and inhibiting cancer growth, while reducing inflammation and oxidative stress.
Implementation Method 1
Such nanoclusters can also induce endoplasmic reticulum stress and inhibit growth of cancerous cells
Implementation Method 2
Additionally, such metallic nanoclusters can be used to inhibit a purinergic P2X7 receptor and FtsH protease
Implementation Method 3
Additionally, such metallic nanoclusters can be used to inhibit a purinergic P2X7 receptor and FtsH protease
Data Source
AI summary
Compositions, methods, and kits are provided for treating infections and cancer with metallic nanoclusters. In particular, metallic nanoclusters having a size of less than 10 nm that are conjugated to adenosine triphosphate (ATP) or an analogue thereof can be used to eradicate a cell in a growth arrest phase such as infectious bacterial or fungal cells. Such nanoclusters can also induce endoplasmic reticulum stress and inhibit growth of cancerous cells. Additionally, such metallic nanoclusters can be used to inhibit a purinergic P2X7 receptor and FtsH protease.