Background: fluorescent nanodiamonds (FND) are nontoxic, infinitely photostable nanoparticles that emit near-infrared fluorescence and have a modifiable surface allowing for the generation of protein–FND conjugates. FND-mediated immune cell targeting may serve as a strategy to visualize immune cells and promote immune cell activation. Methods: uncoated-FND (uFND) were fabricated, coated with glycidol (gFND), and conjugated with immunoglobulin G (IgG–gFND). In vitro studies were performed using a breast cancer/natural killer/monocyte co-culture system, and in vivo studies were performed using a breast cancer mouse model. Results: in vitro studies demonstrated the targeted immune cell uptake of IgG–gFND, resulting in significant immune cell activation and no compromise in immune cell viability. IgG–gFND remained at the tumor site following intratumoral injection compared to uFND which migrated to the liver and kidneys. Conclusion: antibody-conjugated FND may serve as immune drug delivery vehicles with “track and trace capabilities” to promote directed antitumor activity and minimize systemic toxicities.
2 May 2023 in ACS Pharmacology & Translational Science
Introduction: Soft tissue sarcomas are a diverse group of rare cancers, with approximately 15%–20% found in the retroperitoneum. Liposarcomas (LPS) make up approximately half of all retroperitoneal (RP) sarcomas, with most cases classified as either well‐differentiated (WD) or dedifferentiated (DD). DD LPS is more aggressive, with a higher local recurrence rate and risk of distant metastasis compared to WD LPS. The purpose of this review is to outline surgical management of RP LPS and highlight the multimodal treatment strategies for both primary and recurrent disease, along with considerations for their effective implementation. Methods: The current medical literature was reviewed for studies focused on retroperitoneal liposarcoma and its treatment with surgery, radiation, and chemotherapy. The data was interpreted and compiled in the context of expert clinical experience. Results: Along with histopathologic analysis, tumor biology can inform patient prognosis. Surgery, the standard treatment for RP LPS, can be either curative or palliative. In primary disease, an attempt should be made to achieve wide surgical margins when feasible. Surgery for recurrent disease requires careful timing and an understanding of the potential benefit versus risk. Neoadjuvant radiation therapy can improve local control of RP LPS; however, data supporting the use of neoadjuvant chemotherapy are currently lacking. Conclusion: Multimodality treatment of RP LPS is complex and requires consideration of tumor biology and extent of disease, along with individual patient characteristics. Multidisciplinary team collaboration is critical for improving outcomes in patients with RP LPS.
3 October 2022 in Journal of Investigative Dermatology
Fluorescent nanodiamonds (FNDs) are carbon-based nanomaterials that emit bright, photostable fluorescence and exhibit a modifiable surface chemistry. Myeloid-derived suppressor cells (MDSCs) are an immunosuppressive cell population known to expand in cancer patients and contribute to worse patient outcomes. To target MDSC, glycidol-coated FND were conjugated with antibodies against the murine MDSC markers, CD11b and GR1 (dual-Ab FND). In vitro, dual-Ab FND uptake by murine MDSC was significantly higher than IgG-coated FND (94.7% vs. 69.0%, p < 0.05). In vivo, intra-tumorally injected dual-Ab FND primarily localized to the tumor 2 and 24 h post-injection, as measured by in vivo fluorescence imaging and flow cytometry analysis of the spleen and tumor. Dual-Ab FND were preferentially taken up by intra-tumoral MDSC, representing 87.1% and 83.0% of FND+ cells in the tumor 2 and 24 h post-injection, respectively. Treatment of mice with anti-PD-L1 immunotherapy prior to intra-tumoral injection of dual-Ab FND did not significantly alter the uptake of FND by MDSC. These results demonstrate the ability of our novel dual-antibody conjugated FND to target MDSC and reveal a potential strategy for targeted delivery to other specific immune cell populations in future cancer research.