Gold‐based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near‐infrared (NIR‐II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR‐II gold nanostructures, a particular liposome template‐guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR‐II region, affording their capacity of NIR‐II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44‐overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4‐aminothiophenol (4‐ATP) onto AuNFs yields a surface‐enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA‐4‐ATP‐AuNFs‐DOX on tumor‐bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR‐II under PA–Raman dual image‐guided photo‐chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.
Silver sulfide nanoparticles (Ag2S‐NP) hold promise for various optical‐based biomedical applications, such as near‐infrared fluorescence (NIRF) imaging, photoacoustics (PA), and photothermal therapy (PTT). However, their NIR absorbance is relatively low, and previous formulations are synthesized using toxic precursors under harsh conditions and are not effectively cleared due to their large size. Herein, sub‐5 nm Ag2S‐NP are synthesized and encapsulated in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses are conducted using biocompatible, aqueous reagents under ambient conditions. The encapsulation of Ag2S‐NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and PTT effects. AgPCPP nanoparticles exhibit potent contrast properties suitable for PA and NIRF imaging, as well as for computed tomography (CT). Furthermore, AgPCPP nanoparticles readily improve the conspicuity of breast tumors in vivo. Under NIR laser irradiation, AgPCPP nanoparticles significantly reduce breast tumor growth, leading to prolonged survival compared to free Ag2S‐NP. Over time, AgPCPP retention in tissues gradually decreases, without any signs of acute toxicity, providing strong evidence of their safety and biodegradability. Therefore, AgPCPP may serve as a “one‐for‐all” theranostic agent that degrades into small components for excretion after fulfilling diagnostic and therapeutic tasks, offering good prospects for clinical translation.
more » « less- PAR ID:
- 10483278
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
more » « less
Abstract Purpose Ultrasmall silver sulfide nanoparticles (Ag2S-NP) have been identified as promising contrast agents for a number of modalities and in particular for dual-energy mammography. These Ag2S-NP have demonstrated marked advantages over clinically available agents with the ability to generate higher contrast with high biocompatibility. However, current synthesis methods for inorganic nanoparticles are low-throughput and highly time-intensive, limiting the possibility of large animal studies or eventual clinical use of this potential imaging agent.
Methods We herein report the use of a scalable silicon microfluidic system (SSMS) for the large-scale synthesis of Ag2S-NP. Ag2S-NP produced using this system were compared to bulk synthesis and a commercially available microfluidic device through characterization, contrast generation, in vivo imaging, and clearance profiles.
Results Using SSMS chips with 1 channel, 10 parallelized channels, and 256 parallelized channels, we determined that the Ag2S-NP produced were of similar quality as measured by core size, concentration, UV–visible spectrometry, and in vitro contrast generation. Moreover, by combining parallelized chips with increasing reagent concentration, we were able to increase output by an overall factor of 5,100. We also found that
in vivo imaging contrast generation was consistent across synthesis methods and confirmed renal clearance of the ultrasmall nanoparticles. Finally, we found best-in-class clearance of the Ag2S-NP occurred within 24 h.Conclusions These studies have identified a promising method for the large-scale production of Ag2S-NP, paving the way for eventual clinical translation.
-
more » « less
Abstract Triple‐negative breast cancer (TNBC) accounts for 15–25% of breast cancer cases and lacks expression of the three most common receptors seen on other subtypes of breast cancer. This lack of expression makes TNBC unsusceptible to currently available targeted or hormonal therapies, so new treatment strategies are desperately needed. Photothermal therapy (PTT), which utilizes nanoparticles (NPs) embedded in tumors as exogenous energy absorbers to convert externally applied near‐infrared (NIR) light into heat to ablate cancer cells, has shown promise as an alternative strategy. However, it typically uses gold‐based NPs that will remain in the body for extended period of time with unknown long‐term health effects. To enable PTT with biodegradable, polymeric NPs, we encapsulated the NIR‐absorbing dye IR820 in poly(lactic‐
co ‐glycolic acid) (PLGA) NPs. We characterized the physicochemical properties of these IR820‐loaded PLGA NPs and evaluated their performance as PTT agents using bothin vitro andin vivo models of TNBC. The results demonstrate that these NPs are potent mediators of PTT that induce cell death primarily through apoptosis to effectively hinder the growth of TNBC tumors. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1702–1712, 2019. -
more » « less
Abstract Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near‐infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agents for PA imaging. Silver (Ag) is particularly attractive because it has the strongest optical response and highest heat conductivity among plasmonic metals. The results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody‐like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, the AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high‐contrast PA imaging over multiple imaging sessions. Furthermore, the capability of the AgNAs are demonstrated for molecular PA cancer imaging in vivo by incorporating a tumor‐targeting peptide moiety.
-
Protein-functionalized nanoparticles introduce a potentially novel drug delivery method for medical therapeutics, including involvement in cancer therapies and as contrast agents in imaging. Gold and silver nanoparticles are of particular interest due to their distinctive properties. Extensive research shows that gold nanoparticles demonstrate incredible photothermal properties and non-toxic behavior, while silver nanoparticles exhibit antibacterial properties but increase toxicity for human use. However, little is known regarding the properties or applications of hybrid silver-gold particles. This study measured the UV-Vis absorbance spectrum for 40 nm diameter Au, streptavidin-conjugated Au, Ag@Au hybrid, Ag nanoparticles, and Transient Absorbance Spectra of Au. Analysis indicates that the hybrid particles exhibit characteristics of both Ag and Au particles, implying potential applications similar to both Ag and Au nanoparticles.more » « less
