Worldwide nanotechnology development and application have fueled many scientific advances, but technophilic expectations and technophobic demands must be counterbalanced in parallel. Some of the burning issues today are the following: (1) Where is nano today? (2) How good are the communication and investment networks between academia/research and governments? (3) Is there any spotlight application for nanotechnology? Nanomedicine is a particular arm of nanotechnology within the healthcare landscape, focused on diagnosis, treatment, and monitoring of emerging (such as coronavirus disease 2019, COVID-19) and contemporary (including diabetes, cardiovascular diseases, neurodegenerative disorders, and cancer) diseases. However, it may only represent the bright side of the coin. In fact, in the recent past, the concept of nanotoxicology has emerged to address the dark shadows of nanomedicine. The nanomedicine field requires more nanotoxicological studies to identify undesirable effects and guarantee safety. Here, we provide an overall perspective on nanomedicine and nanotoxicology as central pieces of the giant puzzle of nanotechnology. First, the impact of nanotechnology on education and research is highlighted, followed by market trends and scientific output tendencies. In the next section, the nanomedicine and nanotoxicology dilemma is addressed through the interplay of in silico, in vitro, and in vivo models with the support of omics and microfluidic approaches. Lastly, a reflection on the regulatory issues and clinical trials is provided. Finally, some conclusions and future perspectives are proposed for a clearer and safer translation of nanomedicines from the bench to the bedside.

Where Is Nano Today and Where Is It Headed? A Review of Nanomedicine and the Dilemma of Nanotoxicology.

Theranostic nanoparticles with disease-specific administration strategies

Theranostic nanoplatforms integrating diagnostic and therapeutic functions have received considerable attention in the past decade. Among them, hollow manganese (Mn)-based nanoplatforms are superior since they combine the advantages of hollow structures and the intrinsic theranostic features of Mn2+. Specifically, the hollow cavity can encapsulate a variety of small-molecule drugs, such as chemotherapeutic agents, photosensitizers and photothermal agents, for chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. After degradation in the tumor microenvironment (TME), the released Mn2+ is able to act simultaneously as a magnetic resonance (MR) imaging contrast agent (CA) and as a Fenton-like agent for chemodynamic therapy (CDT). More importantly, synergistic treatment outcomes can be realized by reasonable and optimized design of the hollow nanosystems. This review summarizes various Mn-based hollow nanoplatforms, including hollow MnxOy, hollow matrix-supported MnxOy, hollow Mn-doped nanoparticles, hollow Mn complex-based nanoparticles, hollow Mn-cobalt (Co)-based nanoparticles, and hollow Mn-iron (Fe)-based nanoparticles, for MR imaging-guided cancer therapies. Finally, we discuss the potential obstacles and perspectives of these hollow Mn-based nanotheranostics for translational applications. Mn-based hollow nanoplatforms such as hollow MnxOy nanoparticles, hollow matrix-supported MnxOy nanoparticles, Mn-doped hollow nanoparticles, Mn complex-based hollow nanoparticles, hollow Mn-Co-based nanoparticles and hollow Mn-Fe-based nanoparticles show great promise in cancer theranostics. 

/pdf/manganese-based-hollow-nanoplatforms-for-mr-imaging-guided-12q9p6l3.pdf

Manganese-based hollow nanoplatforms for MR imaging-guided cancer therapies

Improving the effectiveness of cancer therapy will require tools that enable more specific cancer targeting and improved tumor visualization. Theranostics have the potential for improving cancer care because of their ability to serve as both diagnostics and therapeutics; however, their diagnostic potential is often limited by tissue-associated light absorption and scattering. Herein, we develop CuInSe2@ZnS:Mn quantum dots (QDs) with intrinsic multifunctionality that both enable the accurate localization of small metastases and act as potent tumor ablation agents. By leveraging the growth kinetics of a ZnS shell on a biocompatible CuInSe2 core, Mn doping, and folic acid functionalization, we produce biocompatible QDs with high near-infrared (NIR)-II fluorescence efficiency up to 31.2%, high contrast on magnetic resonance imaging (MRI), and preferential distribution in 4T1 breast cancer tumors. MRI-enabled contrast of these nanoprobes is sufficient to timely identify small metastases in the lungs, which is critically important for preventing cancer spreading and recurrence. Further, exciting tumor-resident QDs with NIR light produces both fluorescence for tumor visualization through radiative recombination pathways as well as heat and radicals through nonradiative recombination pathways that kill cancer cells and initiate an anticancer immune response, which eliminates tumor and prevents tumor regrowth in 80% of mice.

Bright, Magnetic NIR-II Quantum Dot Probe for Sensitive Dual-Modality Imaging and Intensive Combination Therapy of Cancer.

A vast majority of cancer deaths occur as a result of metastasis. Unfortunately, effective treatments for metastases are currently lacking due to the difficulty of selectively targeting these small, delocalized tumors distributed across a variety of organs. However, nanotechnology holds tremendous promise for improving immunotherapeutic outcomes in patients with metastatic cancer. In contrast to conventional cancer immunotherapies, rationally designed nanomaterials can trigger specific tumoricidal effects, thereby improving immune cell access to major sites of metastasis such as bone, lungs, and lymph nodes, optimizing antigen presentation, and inducing a persistent immune response. This paper reviews the cutting-edge trends in nano-immunoengineering for metastatic cancers with an emphasis on different nano-immunotherapeutic strategies. Specifically, it discusses directly reversing the immunological status of the primary tumor, harnessing the potential of peripheral immune cells, preventing the formation of a pre-metastatic niche, and inhibiting the tumor recurrence through postoperative immunotherapy. Finally, we describe the challenges facing the integration of nanoscale immunomodulators and provide a forward-looking perspective on the innovative nanotechnology-based tools that may ultimately prove effective at eradicating metastatic diseases.

Wen Tang

Papers

Theranostic nanoparticles with disease-specific administration strategies

Nanotechnology-enhanced immunotherapy for metastatic cancer.