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Multimodal particles, methods and uses thereof

A technology of particles, uses, applied in the field of multimodal particles, their uses and uses

Active Publication Date: 2019-12-10
SLOAN KETTERING INST FOR CANCER RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Specifically, there is an important and unmet need for real-time detectors / methods for the precise detection of residual tumors

Method used

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  • Multimodal particles, methods and uses thereof
  • Multimodal particles, methods and uses thereof
  • Multimodal particles, methods and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0168] Example 1: Synthesis of SE(R)RS Particles

[0169] by adding 20 mM HAuCl at 4 °C 4Gold nanostar substrates were synthesized by rapid addition to 40 mM ascorbic acid. Ascorbate-stabilized gold nanostars (about 75 nm, 1 nM) thus synthesized were collected by centrifugation (3,500 xg, 15 min) and dialyzed overnight. Dialyzed gold nanostars were coated with dye-intercalated silica by the typical Stobel method. Briefly, dialyzed gold nanostars were added to ethanol (added with resonance Raman dye, TEOS and ammonia) and allowed to react for 1 hour. Particles were isolated by centrifugation (3,500 xg, 15 min) and washed with ethanol. To achieve PEGylation, the silica surface was modified with mercapto groups by heating the silica-coated nanostars in ethanol containing 1% (v / v) MPTMS at 72°C for 1 hour. The nanostars were washed with ethanol to remove MPTMS and redispersed in 1% (w / v) methoxy-terminated (m)PEG 2000 - maleimide in 10 mM MES buffer (pH 7.1). maleimide-mPEG ...

example 2

[0171] Example 2: Characterization

[0172] Ultra-high sensitivity: such as figure 2 As shown in , the SE(R)RS particles synthesized in Example 1 were characterized by transmission electron microscopy (TEM; JEOL 1200EX (JEOL 1200EX); USA), size distribution, and by nanoparticle tracer analysis (NTA; Nanosight (Nanosight, UK) was used to determine the concentration. Equipped with a 300mW 785nm (near-IR) diode laser and a 1-inch charge-coupled device detector (spectral resolution of 1.07cm -1 Raman activity of equimolar amounts of particles was measured on a Renishaw InVIA Raman microscope (Renishaw InVIA Raman microscope). Raman spectra were analyzed with WiRE 3.4 software (Renishaw, UK).

[0173] Nanoparticle Tracer Analysis (NTA): eg image 3 The size distribution of 1 pM particles in water was determined by NTA as shown in .

example 3

[0174] Example 3: Animal Testing

[0175] refer to Figure 4-10 , injected tumor-bearing mice (dedifferentiated liposarcoma model, PyMT-MMTV (fvb) transgenic breast cancer model, Hi-MYC transgenic prostate cancer model, RCAS) with 150 μL 2.5nM SE(R)RS particles synthesized in Example 1 / TV-a transgenic glioma model). Animals were sacrificed 18 hours later or later and scanned for Raman activity on the system described above. Tumors, organs and lymph nodes were harvested and additionally imaged ex vivo and then embedded in wax. Embedded tissues were processed for histology (H&E staining, tumor marker staining, macrophage staining).

[0176] In Vivo-Ex Vivo Multimodal MRI-Raman Histology Correlation: As confirmed by the experimental results described below, SE(R)RS particles were able to reliably and with microscopic precision delineate three different xenografted mouse sarcomas Presence of tumors in models (n=5 per model). The cells implanted in these mouse models were der...

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Abstract

The present disclosure, among other things, provides a composition of a particle including a substrate; at least a first condensation layer comprising at least a first dopant entity; and at least a second layer comprising a second dopant entity. In some embodiments, different dopant entities are included in different layers. In some embodiments, such dopant entities are or comprise detectable entities. This, in some embodiments, provided technologies achieve multi-modality particles. Among the many advantages of provided technologies include the ability to image particles by a plurality of distinct imaging modalities and / or in a plurality of contexts (e.g., pre-surgical, intraoperative and / or post-surgical environments). The present invention provides methods that include a single administration of particles to a subject, followed by a plurality of steps that comprise imaging the administered particles, which steps may utilize different imaging technologies and / or be performed at different times and / or in different environments.

Description

[0001] Cross References to Related Applications [0002] This application claims priority and benefit to US Provisional Patent Application No. 61 / 739,556, filed December 19, 2012, which is hereby incorporated by reference in its entirety. [0003] governmental support [0004] This invention was made with government support under NIH / NCI K08 CA163961 awarded by the National Institutes of Health. The US Government has certain rights in this invention. Background technique [0005] Nanoparticle systems that can incorporate dopant entities have great potential and are applicable in a variety of situations. There is a continuing need for improved nanoparticle systems for medical and / or non-medical applications. A specific goal of developing such a system is to provide imaging nanoparticles that can be used intraoperatively to define resection boundaries. The completeness of surgical resection greatly affects morbidity and mortality. The challenge and importance of complete...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00C12Q1/02
CPCA61K49/0093A61K49/1824A61K51/1244
Inventor 斯特凡·哈姆森马修·瓦尔莫里茨·基尔舍
Owner SLOAN KETTERING INST FOR CANCER RES
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