Nanomedicine research which covers many fields including drug delivery, cancer therapy vaccine development, antimicrobial diagnostic imaging, wearable device transplantation, and high-throughput screening, has become an important development direction of modern medicine. On July 29th, 2020, Frontiers and Interdisciplinarity in Nanomedicine, the second session of the online academic exchange: Basic and Applied Science: Transformative Discipline Fusion, held by BIO Integration (BIOI), had attracted more than 3000 online viewers and won unanimous praise and recognition from its peers. Herein, we summarize the key points of each talk and we hope that the readers can learn more about integration across scientific fields.
Sangyong Jon: Integration of Naturally Occurring Bioactive Compounds into Nanomedicine
Professor Sangyong Jon, from the Korea Institute of Science and Technology, brought us a report entitled Integration of Naturally Occurring Bioactive Compounds into Nanomedicine. Prior to talking about the main point, he introduced his four major current focus of interest in his lab, namely the development of bipodal peptide binders (aptide) that could be used in numerous clinical applications (i.e. targeting ligand, therapeutic) [1–9], the development of surface-cue-induced cancer stem cells [10], the creation of nanoparticles (NPs) using naturally occurring bioactive compounds [11, 12], and the development of endogenous bilirubin NPs for disease treatment [13–18].
In his presentation, Professor Jon spoke about the study of bilirubin NPs as an example to show how nanomedicine could be combined with naturally occurring active compounds. His research group modified polyethylene glycol (PEG) to improve the biocompatibility of bilirubin NPs in vivo, added the response characteristics of internal and external sources on the basis of the NPs, designed a new drug delivery system, and finally further improved the delivery efficiency of bilirubin for the treatment of tumor and inflammatory diseases. Being trained as an organic chemist, Professor Jon utilized the integration of organic chemistry, bioconjugation techniques, and an endogenous component to realize a simple yet potent and robust nanomedicine for the treatment of various diseases.
Jinjun Shi: RNA Nanomedicine: Integration of Nanotechnology, RNA Delivery, and Biology
Professor Jinjun Shi, a Professor from Harvard Medical School, shared his paper on RNA Nanomedicine: Integration of Nanotechnology, RNA Delivery, and Biology. Professor Shi introduced the most recent RNA-based therapies and their advances in tumor immunotherapy. The bottleneck of RNA-based therapeutics is first and foremost a delivery issue. Having a short half-life (˜5 min), safe and effective delivery of RNAs to a tumor site has been the holy grail in the field. Nevertheless, in-depth study of biomaterials and their properties, their in vivo biological interaction, and the properties of the biomolecules (i.e. siRNA, miRNA, and protein) is crucial in the development of an optimal delivery system.
In Shi’s lab, they utilized the inherent properties of the tumor microenvironment (i.e. high redox level) and used NPs to deliver mRNA that effectively encoded the phosphatase and tensin homolog (PTEN) gene to tumor sites, so as to restore the sensitivity of tumor cells and improve the therapeutic effect of the tumor. This work was published in Nature Biomedical Engineering in 2018 [19].
In addition, Shi’s lab is also working on targeting macrophages in atherosclerotic plagues using polymeric NPs with stabilin-2 peptide targeting. They proved that this NP system works well to reduce atherosclerotic plagues in the blood vessels and therefore is a promising approach to treat systemic arthrosclerosis [20].
Professor Shi emphasized that the combination of the understanding of tumor biology, RNA technology, and nanomedicine will become an important research direction of clinical disease treatment in the future.
Xiaoding Xu: Nanoparticles (NPs)-meditated LncRNA Silencing for Effective Cancer Radiotherapy
Professor Xu Xiaoding, from Sun Yat-Sen Memorial Hospital, Guangzhou, China, presented a paper titled Nanoparticles (NP)s- meditated LncRNA Silencing for Effective Cancer Radiotherapy, and introduced the use of NPs-mediated specific long non-coding RNA (LncRNA) silence to reduce radiotherapy tolerance of patients with triple-negative breast cancer, so as to improve the effect of radiotherapy on the treatment effect and prognosis of patients. In this study, his team first identified a hardcore clinical problem – radioresistance in cancer therapy, for which they investigated the mechanism of this resistance. Using patients’ tumor samples, they carried out omics technology to screen out a novel LncRNA (lncarAP1-AS1), which is one of the top candidates that induces radioresistance in patients with triple negative breast cancer (TNBC).
By using an endosome pH responsive NP previously developed by Professor Xu’s team [21], they developed an NP system that could sustainably deliver the lncRNA AFAP1-AS1 into cancer cells and subsequently into tumors. In an in vivo xenograft model they observed a significant reduction in radioresistance in mice treated with NP(AFAP1-AS1), indicating the feasibility of this nanodelivery system for the clinical intervention of radioresistance.
This elegant work has just been accepted in Advanced Science [Nanoparticles (NPs)-meditated LncRNA AFAP1-AS1Silencing to Block Wnt/β-catenin Signaling Pathway for Synergistic Reversal of Radioresistance and Effective Cancer Radiotherapy].
Zhen Yuan: Photoacoustic Imaging Guided Cancer Theranostics
Professor Zhen Yuan, from the University of Macau, China, presented a wonderful academic report entitled Photoacoustic Imaging Theranostics. In this report, he analyzed the research background of photoacoustic (PA) imaging and photothermal therapy [22–24], artificial intelligence [25], and the challenges they faced in the development of these technics; and combined with the research results of his team, put forward his own unique views on its development and challenges.
Yuan’s team built triangular bovine serum albumin (BSA)-modified copper sulfide (CuS) nanoprobes with near infrared (NIR) absorption, which were expected to be good nanoplatformms for designing multifunctional nanoprobes that involve the molecular imaging for disease diagnosis and personalized treatment guidance [26].
In another study, they constructed an ultrasmall phototheranostic nanoagent, named DPP-BTzTD Pdots. The unique design of low-bandgap D-A p-conjugated polymer (DPP-BTzTD), together with a modified preparation method, allowed the researchers to fabricate Pdots in ultrasmall particle sizes. Extensive experimental tests have demonstrated that the constructed Pdots exhibit excellent photostability, strong NIR-II absorption, good biocompatibility, bright PA signals, and high photothermal conversion efficiency (53%). The experimental results showed that the photothermal imaging and PA imaging mediated by DPP-BTZTD Pdots could effectively capture the structure and function information of tumors, and achieve A significant tumor ablation effect simultaneously [27]. Based on the these advantages, the DPP-BTZTD Pdots has great potential for clinical translation.
From this virtual academic conference, the take-home message today is this: there are many ways to solve a problem, and the solution might be around us. Nanomedicine is not a magic bullet that could solve all the clinical problems, but by integration of various fields, it becomes one of the most effective ways that could interfere with the many points or pathways in various diseases. We applaud all the researchers and scientist that are working hard today to find new interventions for the betterment of human mankind.