Plant-Derived Extracellular Vesicles as Therapeutic Nanocarriers

Mammalian exosomes have emerged as a promising class of functional materials, inspiring novel applications as therapeutic vehicles and nutraceutical compounds. Despite this, their immunogenicity has been an issue of controversy within the scientific community. Although, exosome-like vesicles, innately formed in plants and inherent to eukaryotic cell-derived vesicles, could soothe most of the concerns, they are notably underutilized as therapeutic modalities. This review highlights all efforts published so far, on the use of plant-derived extracellular vesicles (EVs) as therapeutic delivery systems. A summary of the physicochemical characteristics of plant-derived EVs is provided along with their main biological composition and in vitro/in vivo evidence of their therapeutic efficacy provided where available. Despite only a hand full of clinical trials being underway, concerning these vesicles, they arguably possess significant potential as nanodelivery systems of natural origin.

The Extracellular Matrix Enriched With Exosomes for the Treatment on Pulmonary Fibrosis in Mice

Pulmonary fibrosis (PF) is a severe respiratory disease caused by lung microenvironment changes. TGF-β/Smad3 signaling pathway plays a critical role in the fibrotic process. MicroRNA-29 (miR-29) has proved to alleviate the occurrence of PF by downregulating TGF-β/Smad3 signaling pathway. The miRNA application encounters obstacles due to its low stability in body and no targeting to lesions. Exosomes can be used for therapeutic delivery of miRNA due to their favorable delivery properties. However, low efficiency of separation and production impedes the therapeutic application of exosomes. In this study, we developed a liquid natural extracellular matrix (ECM) enriched with miR-29-loaded exosomes for PF treatment. The collagen-binding domain (CBD)-fused Lamp2b (CBD-Lamp2b) and miR-29 were overexpressed in human foreskin fibroblast (HFF) host cells for the entrapment of miR-29-loaded exosomes in ECM of the cells. The repeated freeze-thaw method was performed to prepare the liquid ECM enriched with exosomes without destroying the exosomal membrane. In summary, this study developed a novel functional ECM biomaterial for therapy of PF, and also provided a promising gene therapy platform for different diseases by treatment with liquid ECM that is, enriched with exosomes loaded with different functional miRNAs.

A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod

Agonists for toll-like receptors (TLRs) have shown promising activities against cancer. In the present study, a squalene-based nanoemulsion (NE) was loaded with resiquimod, a TLR7/8 agonist for therapeutic delivery. R848 NE was developed and characterized for long-term stability. In vitro and in vivo antitumor immunity of R848 NE were also evaluated in combination with SD-101, a CpG-containing TLR9 agonist. In vitro studies demonstrated strong long-term stability and immune responses to R848 NE. When combined with SD-101, strong antitumor activity was observed in MC38 murine colon carcinoma model with over 80% tumor growth inhibition. The combination treatment showed a 4-fold increase in systemic TNFa production and a 2.6-fold increase in Cd8a expression in tumor tissues, suggesting strong cell-mediated immune responses against the tumor. The treatment not only demonstrated a strong antitumor immunity by TLR7/8 and TLR9 activations but also induced PD-L1 upregulation in tumors, suggesting a potential therapeutic synergy with immune checkpoint inhibitors.

The Role of Exosomes and Their Applications in Cancer

Exosomes are very small extracellular vesicles secreted by multiple cell types and are extensively distributed in various biological fluids. Recent research indicated that exosomes can participate in regulating the tumor microenvironment and impacting tumor proliferation and progression. Due to the extensive enrollment in cancer development, exosomes have become a focus of the search for a new therapeutic method for cancer. Exosomes can be utilized for the therapeutic delivery of small molecules, proteins and RNAs to target cancer cells with a high efficiency. Exosome-carried proteins, lipids and nucleic acids are being tested as promising biomarkers for cancer diagnosis and prognosis, even as potential treatment targets for cancer. Moreover, different sources of exosomes exhibit multiple performances in cancer applications. In this review, we elaborate on the specific mechanism by which exosomes affect the communication between tumors and the microenvironment and state the therapeutic and diagnostic applications of exosomes in cancers.

BH3-mimetics: recent developments in cancer therapy

The hopeful outcomes from 30 years of research in BH3-mimetics have indeed served a number of solid paradigms for targeting intermediates from the apoptosis pathway in a variety of diseased states. Not only have such rational approaches in drug design yielded several key therapeutics, such outputs have also offered insights into the integrated mechanistic aspects of basic and clinical research at the genetics level for the future. In no other area of medical research have the effects of such work been felt, than in cancer research, through targeting the BAX-Bcl-2 protein-protein interactions. With these promising outputs in mind, several mimetics, and their potential therapeutic applications, have also been developed for several other pathological conditions, such as cardiovascular disease and tissue fibrosis, thus highlighting the universal importance of the intrinsic arm of the apoptosis pathway and its input to general tissue homeostasis. Considering such recent developments, and in a field that has generated so much scientific interest, we take stock of how the broadening area of BH3-mimetics has developed and diversified, with a focus on their uses in single and combined cancer treatment regimens and recently explored therapeutic delivery methods that may aid the development of future therapeutics of this nature.

The latest developments in the area of therapeutic delivery excluding some diseases, such as COVID-19 and the big three (HIV/AID, malaria and tuberculosis)

Summary It is the beginning of a new decade, where COVID-19 and the ‘big three’ (HIV/AID, malaria and tuberculosis) have raised public awareness of the type of challenges researchers face every day. Beyond these diseases, there are also still many more for which scientists are working to develop new therapies and their impact in healthcare is enormous too. This industry update covers the period 1–31 August 2021, and some examples of research and approvals for many other diseases excluding COVID-19 and the ‘big three’ are presented. There is a progressive trend of approvals of novel drug candidates and the proposal of new indications for the existing ones. Some patents related to rare diseases were also published during this month. Information and analyses were sourced from scientific literature, regulatory and patent agencies, websites and press releases of the companies (and not based upon personal opinion). The main reason of leaving COVID-19 research outside the scope of this update is mainly due to the rapid growth and change in this field; some preliminary results require further research and scientists must be aware of the final impact that this research could have on public opinion. Moreover, as a result of disruptions to health care in the face of COVID-19, several research groups simply stopped their research in other diseases and, for that reason, it is imperative to sum up some important advances in other critical diseases and health areas.