In vivophotoacoustic imaging of breast cancer tumor with HER2-targeted nanodiamonds

Abstract

Radiation-damaged nanodiamonds (NDs) are ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their good biocompatibility and high optical absorbance in the near-infrared (NIR) range. Acid treated NDs are oxidized to form carboxyl groups on the surface, functionalized with polyethylene glycol (PEG) and human epidermal growth factor receptor 2 (HER2) targeting ligand for breast cancer tumor imaging. Because of the specific binding of the ligand conjugated NDs to the HER2-overexpressing murine breast cancer cells (4T1.2 neu), the tumor tissues are significantly delineated from the surrounding normal tissue at wavelength of 820 nm under the PA imaging modality. Moreover, HER2 targeted NDs (HER2-PEG-NDs) result in higher accumulation in HER2 positive breast tumors as compared to non-targeted NDs after intravenous injection (i.v.). Longer retention time of HER-PEG-NDs is observed in HER2 overexpressing tumor model than that in negative tumor model (4T1.2). This demonstrates that targeting moiety conjugated NDs have great potential for the sensitive detection of cancer tumors and provide an attractive delivery strategy for anti-cancer drugs.

Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor α_IIbβ₃ and activated platelets

“…However, for in vivo imaging aimed as a medical diagnostic of said lesions, NIR-emitting F-NDPs would likely be more advantageous. 11,13 The innate ability of NIR light to penetrate biological tissues with limited interference from endogenous fluorophores has already been demonstrated in studies where certain elements of blood clots, such as fibrin, were detected in vivo. 12 The NIR technology is expected to afford extracorporeal, telemetry-based, "on line" assessment of blood clots using ambulatory facilities for the accurate, large-scale assessment of cardiovascular risk of TEE.…”

“…4 Of particular interest are carbon-based particles, such as nanodiamond particles (NDPs), which have been functionalized for diverse applications, 5 such as drug discovery, [6][7][8] drug delivery, 9,10 and imaging of pathological sites in vivo. 9,[11][12][13] More recently, special attention is focused on NDPs that can be excited optically to emit fluorescent light (F-NDPs) at various wavelengths, especially in the near infrared (NIR) range. 11,12 The innate ability of these new-generation NIR-emitting F-NDPs to report from within biological tissues with limited interference from endogenous fluorophores has already been demonstrated in studies, where certain elements of blood clots, such as fibrin, were detected in vivo.…”

Targeted contrast agents and activatable probes for photoacoustic imaging of cancer

“…72 With respect to the development of TCA for PA imaging, a number of exciting studies have been reported targeting various members of the ErbB family. 16,17,53,73–84…”

Photoacoustic Imaging for Management of Breast Cancer: A Literature Review and Future Perspectives

“…Zhang et al [76] performed PA imaging at 820 nm in a mouse model to evaluate the feasibility of using non-fluorescent nanodiamond as PA imaging contrast agents for effective HER2 positive breast cancer detection. Balasundaram et al [77] performed an in vivo PA imaging study with folate-conjugated polymer (CP) dots as contrast agents in xenograft mice models and they demonstrated that after 1 h of the injection of the contrast agents, the Folate-CP dots accumulated into the tumor site produced fourfold contrast-enhanced PA signal as compared to PA signals produced by CP dots.…”