BIOI Virtual Academic Series PART 2: Frontiers and Multidisciplinarity in Nanomedicine

Nanomedicine research which covers many fields including drug delivery, cancer therapy vaccine development, anti­ microbial diagnostic imaging, wearable device transplanta­ tion, and high­throughput 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.


Phei Er Saw Executive Editor
Nanomedicine research which covers many fields including drug delivery, cancer therapy vaccine development, anti microbial diagnostic imaging, wearable device transplanta tion, and highthroughput screening, has become an important development direction of modern medicine. On July 29 th , 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.
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 bili rubin 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 RNAbased therapies and their advances in tumor immunotherapy. The bottleneck of RNA based therapeutics is first and foremost a delivery issue. Having a short halflife (~5 min), safe and effective delivery of RNAs to a tumor site has been the holy grail in the field. Nevertheless, indepth 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 phos phatase 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 mac rophages in atherosclerotic plagues using polymeric NPs with stabilin2 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 nano medicine will become an important research direction of clin ical disease treatment in the future.

Xiaoding Xu: Nanoparticles (NPs)meditated LncRNA Silencing for Effective Cancer Radiotherapy
Professor Xu Xiaoding, from Sun YatSen Memorial Hospital, Guangzhou, China, presented a paper titled Nanoparticles (NP)s meditated LncRNA Silencing for Effective Cancer Radiotherapy, and introduced the use of NPsmediated specific long noncoding RNA (LncRNA) silence to reduce radiother apy tolerance of patients with triplenegative breast cancer, so as to improve the effect of radiotherapy on the treatment effect and pro gnosis 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 techno logy to screen out a novel LncRNA (lncarAP1AS1), 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 devel oped by Professor Xu's team [21], they developed an NP sys tem that could sustainably deliver the lncRNA AFAP1AS1 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(AFAP1AS1), indi cating the feasibility of this nanodelivery system for the clin ical intervention of radioresistance.
This elegant work has just been accepted in Advanced Science [Nanoparticles (NPs)meditated LncRNA AFAP1 AS1Silencing to Block Wnt/βcatenin 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, pre sented a wonderful academic report entitled Photoacoustic Imaging Theranostics. In this report, he ana lyzed the research background of photoacoustic (PA) imaging and photothermal therapy [22][23][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 photother anostic nanoagent, named DPPBTzTD Pdots. The unique design of lowbandgap DA pconjugated polymer (DPP BTzTD), together with a modified preparation method, allowed the researchers to fabricate Pdots in ultrasmall par ticle sizes. Extensive experimental tests have demonstrated that the constructed Pdots exhibit excellent photostability, strong NIRII 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 DPPBTZTD Pdots could effectively capture the structure and function infor mation of tumors, and achieve A significant tumor ablation effect simultaneously [27]. Based on the these advantages, the DPPBTZTD Pdots has great potential for clinical translation.
From this virtual academic conference, the takehome message today is this: there are many ways to solve a prob lem, and the solution might be around us. Nanomedicine is not a magic bullet that could solve all the clinical prob lems, 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.