Determination of the supramolecular organization of encapsulated molecules by luminescence lifetime analysis

Patent metadata

Field	Value
Publication number	US-11913882-B2
Application number	US-202118252202-A
Country	US
Kind code	B2
Filing date	Nov 8, 2021
Priority date	Nov 9, 2020
Publication date	Feb 27, 2024
Grant date	Feb 27, 2024

Abstract

A determination of supramolecular organization in a substance includes target molecules and nanocarriers at least one of which is luminescent, based on a step of collecting of lifetime decay data of at least a standard substance pure or substantially pure where a known organization state of the target molecules and the nanocarriers is pure or substantially pure; and a step of comparing the standard data and test data from a test substance.

First claim

What is claimed is:

1. A determination method of a supramolecular organization of target luminescent molecules encapsulated within nanocarrier particles by a lifetime analysis comprising the steps of:
defining at least a first supramolecular organization of a plurality of target luminescent molecules and/or the nanocarrier particles, wherein the plurality of target luminescent molecules and/or the nanocarrier particles are substantially organized and optionally the nanocarrier particle is further luminescent;
receiving at least a first standard luminescence lifetime dataset representing a first decay associated to a first standard substance where the plurality of target luminescent molecules and/or the nanocarrier particles are substantially organized according to the first supramolecular organization;
processing a test substance comprising nanocarriers with the plurality of target luminescent molecules to obtain a test luminescence lifetime dataset of the test substance comprising a target luminescent molecule having an unknown supramolecular organization;
quantitatively comparing the test luminescence lifetime dataset and the at least first standard luminescence lifetime dataset;
determining whether a second supramolecular organization of the plurality of target luminescent molecules and the nanocarrier particles is present or not in the test substance based on a quantitative superimposition of the test luminescence lifetime dataset and the first standard luminescence lifetime dataset.

2. The determination method according to claim 1 , wherein:
the step of defining comprises at least a second or more supramolecular organizations of the plurality of target luminescent molecules;
the step of receiving comprises a second or more standard luminescence lifetime datasets representing a second decay associated to a first standard substance where the plurality of target luminescent molecules and/or the nanocarrier particles are substantially organized according to the second or more supramolecular organizations; and
the step of determining comprises whether a further supramolecular organization of the plurality of target luminescent molecules and/or the nanocarrier particles is present in the test substance based on whether test substance luminescence lifetime data is a linear combination of the standard luminescence lifetime dataset.

3. The determination method according to claim 2 , further comprising the steps of:
identifying a number of iterations for at least two supramolecular organization states;
collecting comparison luminescence lifetime data from a comparison substance generated so as not to show at least one of the at least two supramolecular organization states of the plurality of target luminescent molecules and the nanocarrier particles; and
comparing the test substance luminescence lifetime data and the comparison luminescence lifetime data to confirm whether the number of iterations indicates a total number of standard supramolecular organization states of the plurality of target luminescent molecules present within the test substance.

4. The determination method according to claim 3 , wherein the luminescence lifetime data are either fitted exponential decay data or phasor plot data.

5. The determination method according to claim 4 , wherein a fitting exponential decay comprises the calculation of a i-th weight A i attributable to each i-th putative organization state and a i-th characteristic lifetime attributable to each i-th putative organization state is already assigned from an i-th standard luminescence lifetime dataset obtained in the step of receiving.

6. The determination method according to claim 1 comprising an additional step of quantifying a fractional intensity contribution of each defined supramolecular organization of the plurality of target luminescent molecules and/or the nanocarrier.

7. The determination method according to claim 1 , wherein the target luminescent molecule or nanocarrier is a drug.

8. The determination method according to claim 1 , wherein standard luminescence lifetime data are mono-exponential.

Assignees

• Scuola Normale Superiore
• Univ Degli Studi Di Roma “La Sapienza”
• Fondazione St Italiano Tecnologia

Inventors

• Cardarelli Francesco
• Beltram Fabio
• Tentori Paolo Maria
• Caracciolo Giulio
• Pozzi Daniela

Classifications

• G01N21/6408 Primary

  with measurement of decay time, time resolved fluorescence · CPC title

• G01N33/15

  Medicinal preparations {; Physical properties thereof, e.g. dissolubility} · CPC title