An official website of the United States government
Cancer is a global health problem in need of transformative treatment solutions for improved patient outcomes. Many conventional treatments prove ineffective and produce undesirable side effects because they are incapable of targeting only cancer cells within tumors and metastases post administration. There is a desperate need for targeted therapies that can maximize treatment success and minimize toxicity. Nanoparticles (NPs) with tunable physicochemical properties have potential to meet the need for high precision cancer therapies. At the forefront of nanomedicine is biomimetic nanotechnology, which hides NPs from the immune system and provides superior targeting capabilities by cloaking NPs in cell-derived membranes. Cancer cell membranes expressing “markers of self” and “self-recognition molecules” can be removed from cancer cells and wrapped around a variety of NPs, providing homotypic targeting and circumventing the challenge of synthetically replicating natural cell surfaces. Compared to unwrapped NPs, cancer cell membrane-wrapped NPs (CCNPs) provide reduced accumulation in healthy tissues and higher accumulation in tumors and metastases. The unique biointerfacing capabilities of CCNPs enable their use as targeted nanovehicles for enhanced drug delivery, localized phototherapy, intensified imaging, or more potent immunotherapy. This review summarizes the state-of-the-art in CCNP technology and provides insight to the path forward for clinical implementation.
more »
« less
Biomimetic Nanoparticles for the Treatment of Hematologic Malignancies
Hematologic malignancies are a prevalent group of cancers that originate from abnormal hematopoietic stem cells (HSCs) in the bone marrow. As these cells differentiate to produce all blood cell types, their mutation and/or abnormal differentiation results in a wide range of diseases and complications. Current treatments for hematologic maligancies include chemotherapy and HSC transplants, both of which engender detrimental side effects that the patient must endure, and the end result is still often death. Thus, there exists a dire need for alternative methods to treat hematologic malignancies. Researchers have recently begun to explore the use of biomimetic nanotherapeutic to treat these cancers and mitigate their side effects, with promising results. Biomimetic nanoparticles (NPs) imitate naturally occurring structures such as cells through various techniques to avoid immune recognition and target specific locations in the body; by exploiting cells’ expression of “self‐recognition” molecules and their unique homing abilities, biomimetic NPs can deliver therapeutic cargo precisely to diseased cells while minimizing risks of toxicity. Herein, several biomimetic nanomedicines are reviewed that are investigated as treatments for hematologic malignancies and offers perspective on the future of this approach as a therapeutic strategy.
more »
« less
- Award ID(s):
- 1752009
- PAR ID:
- 10213155
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced NanoBiomed Research
- Volume:
- 1
- Issue:
- 4
- ISSN:
- 2699-9307
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Vascular restenosis is a major complication in recanalized arteries. Nanoparticles (NPs) have shown great promise as delivery systems in advancing strategies to treat such vascular anomalies. By enabling precise targeting, NPs can overcome the challenges of low drug efficacy and off-target effects. Here we present a biomimetic in vitro platform comprised of 3D bioprinting, nanomaterials, and perfusion technologies, to study the use of NP targeting to address endothelial overgrowth. We bioprinted 3D vascular channels at high fidelity, using gelatin methacrylate as bioink, with artery-like stiffness. Human endothelial cells (ECs) were used to endothelialize the printed channels. GFP-labelled superparamagnetic iron oxide NPs (SPIONs), loaded with the Rapamune anti-proliferative drug, were perfused through the bifurcated artery model at physiological rate. Computational modeling predicted greatest level of alterations in wall shear stress in the conduit’s junction with the artery, identifying this region prone to restenosis. A neodymium disc magnet was embedded in the printed tissue to attract the therapeutic SPIONs to the region of high risk. In vitro dynamic culture was conducted for 2 wks. We assessed cell viability, proliferation, and function using AlamarBlue and immunohistochemistry. Results showed significant targeted effect of NP delivery in reducing EC overgrowth. This platform enables design of precise targeting of therapeutics to treat a variety of cardiovascular diseases at a high spatial and temporal control.more » « less
-
Abstract White blood cells (WBCs) are immune cells that play essential roles in critical diseases including cancers, infections, and inflammatory disorders. Their dynamic and diverse functions have inspired the development of WBC membrane‐coated nanoparticles (denoted “WBC‐NPs”), which are formed by fusing the plasma membranes of WBCs, such as macrophages, neutrophils, T cells, and natural killer cells, onto synthetic nanoparticle cores. Inheriting the entire source cell antigens, WBC‐NPs act as source cell decoys and simulate their broad biointerfacing properties with intriguing therapeutic potentials. Herein, the recent development and medical applications of WBC‐NPs focusing on four areas, including WBC‐NPs as carriers for drug delivery, as countermeasures for biological neutralization, as nanovaccines for immune modulation, and as tools for the isolation of circulating tumor cells and fundamental research is reviewed. Overall, the recent development and studies of WBC‐NPs have established the platform as versatile nanotherapeutics and tools with broad medical application potentials.more » « less
-
Background Nanoparticles (NPs) hold promise as alternatives to antibiotics in the fight against multi-drug-resistant bacteria. However, concerns about their cytotoxicity, particularly their effects on mammalian cells, must be thoroughly addressed to ensure therapeutic safety. Amphiphilic Janus NPs, which have segregated hydrophobic and polycationic ligands on two hemispheres, have previously been shown to exhibit potent antibacterial activity. Methods In this study, we evaluated the cytotoxicity of amphiphilic Janus NPs in immune and cancer cell lines. Cytotoxicity assays were performed to assess the effects of Janus NPs on cell viability and membrane integrity, with a particular focus on how internalization of the nanoparticles influenced cellular responses. Results The results revealed that both immune and cancer cells exhibited negligible cytotoxic effects when exposed to Janus NPs. However, phagocytic immune cells demonstrated greater susceptibility to membrane damage and viability loss, suggesting that internalization plays a significant role in nanoparticle-induced cytotoxicity. Conclusions Amphiphilic Janus NPs show great potential as highly effective antibacterial agents with minimal cytotoxicity. While immune cells may be more vulnerable to nanoparticle-induced damage due to their internalization capacity, these findings support the further investigation of Janus NPs for clinical applications.more » « less
-
BackgroundCurative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses. MethodsIn this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify Tpex recruitment capabilities at tolerable cytokine doses. ResultsWe show IL-12 cytokine factories can effectively treat a broad spectrum of cancer types. Single-cell RNA sequencing data suggests that the antitumor efficacy seen in our studies was due to retinal pigmented epithelial cells-mIL12 treatment inducing differentiation of Tpex cells within the tumor microenvironment. When administered in combination with checkpoint therapy, IL-12 cytokine factory treatment generated systemic abscopal immunity, preventing subcutaneous tumor outgrowth in 8/9 mice with colorectal cancer and lung metastasis in mice with melanoma. Furthermore, this platform was well tolerated in a non-human primate without signs of toxicity. ConclusionsOur new immunotherapy approach provides a robust strategy for inducing Tpex recruitment and systemic immunity against a range of solid peritoneal malignancies, many incurable with current immunotherapy strategies. Notably, these features were achieved using IL-12, and by leveraging our technology, we avoided the toxicities that have prevented the translation of IL-12 to the clinic. Our findings provide a strong rationale for the clinical development of IL-12 cytokine factories.more » « less
