An Iron Oxide Nanocarrier for dsRNA to Target Lymph Nodes and Strongly Activate Cells of the Immune System

The success of nanoparticle‐based therapies will depend in part on accurate delivery to target receptors and organs. There is, therefore, considerable potential in nanoparticles which achieve delivery of the right drug(s) using the right route of administration to the right location at the right time, monitoring the process by non‐invasive molecular imaging. A challenge is harnessing immunotherapy via activation of Toll‐like receptors (TLRs) for the development of vaccines against major infectious diseases and cancer. In immunotherapy, delivery of the vaccine components to lymph nodes (LNs) is essential for effective stimulation of the immune response. Although some promising advances have been made, delivering therapeutics to LNs remains challenging. It is here shown that iron‐oxide nanoparticles can be engineered to combine in a single and small (<50 nm) nanocarrier complementary multimodal imaging features with the immunostimulatory activity of polyinosinic‐polycytidylic acid (poly (I:C)). Whilst the fluorescence properties of the nanocarrier show effective delivery to endosomes and TLR3 in antigen presenting cells, MRI/SPECT imaging reveals effective delivery to LNs. Importantly, in vitro and in vivo studies show that, using this nanocarrier, the immunostimulatory activity of poly (I:C) is greatly enhanced. These nanocarriers have considerable potential for cancer diagnosis and the development of new targeted and programmable immunotherapies.     

Precision Delivery of Dual Immune Inhibitors Loaded Nanomodulator to Reverse Immune Suppression for Combinational Photothermal-Immunotherapy (Small 21/2023)

Although photothermal therapy (PTT) can noninvasively kill tumor cells and exert synergistic immunological effects, the immune responses are usually harmed due to the lack of cytotoxic T cells (CTLs) pre-infiltration and co-existing of intricate immunosuppressive tumor microenvironment (TME), including the programmed cell death ligand 1 (PD-L1)/cluster of differentiation 47 (CD47)/regulatory T cells (Tregs)/M2-macrophages overexpression. Indoleamine 2, 3-dioxygenase inhibitor (NLG919) or bromodomain extra-terminal inhibitor (OTX015) holds great promise to reprogram suppressive TME through different pathways, but their collaborative application remains a formidable challenge because of the poor water solubility and low tumor targeting. To address this challenge, a desirable nanomodulator based on dual immune inhibitors loaded mesoporous polydopamine nanoparticles is designed. This nanomodulator exhibits excellent biocompatibility and water solubility, PTT, and bimodal magnetic resonance/photoacoustic imaging abilities. Owing to enhanced permeability and retention effect and tumor acidic pH-responsiveness, both inhibitors are precisely delivered and locally released at tumor sites. Such a nanomodulator significantly reverses the immune suppression of PD-L1/CD47/Tregs, promotes the activation of CTLs, regulates M2-macrophages polarization, and further boosts combined therapeutic efficacy, inducing a strong immunological memory. Taken together, the nanomodulator provides a practical approach for combinational photothermal-immunotherapy, which may be further broadened to other “immune cold” tumors.     

Drug delivery: Logic‐Embedded Vectors for Intracellular Partitioning,Endosomal Escape,and Exocytosis of Nanoparticles (Small 23/2010)

A new generation of nanocarriers, logic‐embedded vectors (LEVs), is endowed with the ability to localize components at multiple intracellular sites, thus creating an opportunity for synergistic control of redundant or dual‐hit pathways. LEV encoding elements include size, shape, charge, and surface chemistry. In this study, LEVs consist of porous silicon nanocarriers, programmed for cellular uptake and trafficking along the endosomal pathway, and surface‐tailored iron oxide nanoparticles, programmed for endosomal sorting and partitioning of particles into unique cellular locations. In the presence of persistent endosomal localization of silicon nanocarriers, amine‐functionalized nanoparticles are sorted into multiple vesicular bodies that form novel membrane‐bound compartments compatible with cellular secretion, while chitosan‐coated nanoparticles escape from endosomes and enter the cytosol. Encapsulation within the porous silicon matrix protects these nanoparticle surface‐tailored properties, and enhances endosomal escape of chitosan‐coated nanoparticles. Thus, LEVs provide a mechanism for shielded transport of nanoparticles to the lesion, cellular manipulation at multiple levels, and a means for targeting both within and between cells.