Nanodepots Encapsulating a Latency Reversing Agent and Broadly Neutralizing Antibody Enhance Natural Killer Cell Cytotoxicity Against an in vitro Model of Latent HIV.

Purpose: Current antiretroviral therapies (ART) for human immunodeficiency virus (HIV) are not curative, as the virus persists in latent reservoirs, requiring lifelong adherence to ART and increasing the risk of co-morbidities. "Shock and kill" approaches to reactivate HIV from latent reservoirs followed by administration of anti-HIV drugs represent a promising strategy for eradicating latent HIV. To achieve effective shock and kill, we describe a strategy to eradicate the HIV reservoir that combines latency reversing agents (LRAs), broadly neutralizing antibodies (bnAbs), and natural killer (NK) cells.

Nano-formulations for bone-specific delivery of siRNA for silencing-induced regulation of bone formation and resorption to maximize therapeutic potential for bone-related diseases.

CrkII, a member of the adaptor protein family, is known to participate in bone homeostasis the regulation of osteoclasts and osteoblasts. Therefore, silencing would beneficially impact the bone microenvironment. In this study, siRNA encapsulated by a bone-targeting peptide (AspSerSer)-liposome was evaluated for its therapeutic applications using a receptor activator of nuclear factor kappa-B ligand (RANKL)-induced bone loss model.

A sugar modified amphiphilic cationic nano-adjuvant ceased tumor immune suppression and rejuvenated peptide vaccine induced antitumor immunity in cervical cancer.

Human papilloma virus (HPV), one of the most common cancer-causing viruses, accounts for more than 90% of human anal and cervical cancers. Clinical studies have focused on adjuvant therapy with vaccines to improve therapeutic outcomes in patients with late-stage HPV-related cancers. In the present study, a mannose receptor (CD206) targeting a lithocholic acid-modified polyethylenimine (PEI) nano-adjuvant delivering the toll-like receptor 7/8 agonist, resiquimod (R848) (mLAPMi-R848), in a HPV E6- and E7-expressing TC-1 tumor murine model was developed.

Resolution of MoS Nanosheets-Induced Pulmonary Inflammation Driven by Nanoscale Intracellular Transformation and Extracellular-Vesicle Shuttles.

Pulmonary exposure to some engineered nanomaterials can cause chronic lesions as a result of unresolved inflammation. Among 2D nanomaterials and graphene, MoS has received tremendous attention in optoelectronics and nanomedicine. Here an integrated approach is proposed to follow up the transformation of MoS nanosheets at the nanoscale and assesss their impact on lung inflammation status over 1 month after a single inhalation in mice.

Development of extracellular vesicle-based medicinal products: A position paper of the group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France".

Extracellular vesicles (EV) are emergent therapeutic effectors that have reached clinical trial investigation. To translate EV-based therapeutic to clinic, the challenge is to demonstrate quality, safety, and efficacy, as required for any medicinal product. EV research translation into medicinal products is an exciting and challenging perspective.

Engineering and loading therapeutic extracellular vesicles for clinical translation: A data reporting frame for comparability.

Extracellular vesicles (EVs) have emerged as new drug delivery systems as well as a regenerative cell-free effectors going beyond academic research to reach industrial research and development (R&D). Many proof-of-concept studies are now published describing the delivery of drugs, nanoparticles or biologics among which nucleic acids, proteins, viruses, etc. Their main interests rely on their intrinsic biocompatibility, targeting capabilities and biological activities.

Combination of Photodynamic Therapy and a Flagellin-Adjuvanted Cancer Vaccine Potentiated the Anti-PD-1-Mediated Melanoma Suppression.

Immune checkpoint inhibitors become a standard therapy for malignant melanoma. As immune checkpoint inhibitor monotherapies proved to have limited efficacy in significant portion of patients, it is envisaged that combination with other therapeutic modalities may improve clinical outcomes. We investigated the effect of combining photodynamic therapy (PDT) and TLR5 agonist flagellin-adjuvanted tumor-specific peptide vaccination (FlaB-Vax) on the promotion of PD-1 blockade-mediated melanoma suppression using a mouse B16-F10 implantation model.

Role of Immunosuppressive Microenvironment in Acquiring Immunotolerance Post-Photothermal Therapy.

Background: Nanoparticle-mediated photothermal therapy (PTT) has been well studied as a treatment for cancer. However, the therapeutic outcome of PTT is often hindered by the penetration depth of laser light. In the tumor margin beyond the laser penetration limit, tumor recurrence often occurs, bypassing the immune response of the host.

"Navigate-dock-activate" anti-tumor strategy: Tumor micromilieu charge-switchable, hierarchically activated nanoplatform with ultrarapid tumor-tropic accumulation for trackable photothermal/chemotherapy.

The delivery of therapeutics into tumors remains a challenge in nanoparticle-mediated drug delivery. However, effective therapies such as photothermal therapy (PTT) are limited by quick systemic clearance and non-specific biodistribution. Anti-tumor strategies tailored to accommodate both tumor accumulation/retention and cellular internalization under a single platform would be a promising strategy.

In Situ Oxygenic Nanopods Targeting Tumor Adaption to Hypoxia Potentiate Image-Guided Photothermal Therapy.

Tumor adaption to hypoxic stress not only plays a crucial role in tumor malignancy but also can protect cancer cells from therapeutic interventions. Hence, therapeutic strategies attenuating tumor hypoxia in conjunction with conventional therapies may be an ideal approach. Here, we report the application of in situ oxygenic carbon nano-onion (CNO)/manganese oxide nanopods (iOCOMs) as novel theranostic photothermal transducers to neutralize the oncogenic influence of the hypoxic tumor microenvironment (TME).

Design of an Amphiphilic Poly(aspartamide)-mediated Self-assembled Nanoconstruct for Long-Term Tumor Targeting and Bioimaging.

Biodegradable polymers have been developed for the targeted delivery of therapeutics to tumors. However, tumor targeting and imaging are usually limited by systemic clearance and non-specific adsorption. In this study, we used poly(amino acid) derivatives, such as poly(succinimide), to synthesize a nanomicelle-forming poly(hydroxyethylaspartamide) (PHEA, P) modified sequentially with octadecylamine, polyethylene glycol (PEG, P), and glycine (G) to design PHEA-PEG-glycine (PPG) nanoparticles (NPs).

Magnetic field-inducible drug-eluting nanoparticles for image-guided thermo-chemotherapy.

Multifunctional nanoparticles integrating cancer cell imaging and treatment modalities into a single platform are recognized as a promising approach; however, their development currently remains a challenge. In this study, we synthesized magnetic field-inducible drug-eluting nanoparticles (MIDENs) by embedding superparamagnetic iron oxide nanoparticles (FeO; SPIONs) and cancer therapeutic drugs (doxorubicin; DOX) in a temperature-responsive poly (lactic-co-glycolic acid) (PLGA) nanomatrix. Application of an external alternating magnetic field (AMF) generated heat above 42 °C and subsequent transition of the PLGA polymer matrix (T = 42-45 °C) from the glassy to the rubbery state, facilitating the controlled release of the loaded DOX, ultimately allowing for simultaneous hyperthermia and local heat-triggered chemotherapy for efficient dual cancer treatment.

CD44 targeting biocompatible and biodegradable hyaluronic acid cross-linked zein nanogels for curcumin delivery to cancer cells: In vitro and in vivo evaluation.

In this study, we developed novel hyaluronic acid cross-linked zein nanogels (HA-Zein NGs) to deliver the potential anticancer agent curcumin (CRC), a naturally occurring phytochemical drug in cancer cells. In vitro studies showed that they are highly compatible with the tested cell lines. They showed CD44 specific uptake in CT26 cell line more than by the CD44 receptor pre-inhibited CT26 cells.

Programmed 'triple-mode' anti-tumor therapy: Improving peritoneal retention, tumor penetration and activatable drug release properties for effective inhibition of peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) is a fatal condition arising in the gastrointestinal tract. PC patients administered drugs locally in the tumor region, such as in intraperitoneal chemotherapy (IPCh), suffer from low drug retention time and tumor penetration. Herein, we synthesized a lithocholic acid (LCA)-conjugated disulfide-linked polyethyleneimine (ssPEI) micelle (LAPMi) nanoconstruct by covalently conjugating ssPEI and LCA, thereby forming positive charged nanomicellar structures loaded with paclitaxel (PTX) (LAPMi-PTX) for IPCh.

Dual-stimuli-responsive albumin-polyplex nanoassembly for spatially controlled gene release in metastatic breast cancer.

Stimuli-responsive polymeric nanoparticles are useful for overcoming challenges such as transfection efficiency and the specific and safe delivery of genes to cancer cells. Transfection outcomes can be improved through spatially and temporally controlled gene release. We formulated a nanoassembly comprising a disulfide-crosslinked polyethylenimine (ssPEI) conjugated with a tumor-specific cell-penetrating peptide (DS 4-3) (SPD) polyplex and bovine serum albumin (BSA)-loaded IR780 (BI) nanoparticle, thereby forming a dual-stimulus-triggered, tumor-penetrating and gene-carrying nanoassembly (BI-SPD) via electrostatic complexing.

A targeted graphene nanoplatform carrying histamine dihydrochloride for effective inhibition of leukemia-induced immunosuppression.

Despite the introduction of many efficient post-consolidation therapies for complete relapse in leukemia patients, many patients suffer from relapse. Reactive oxygen species (ROS) are considered an important parameter in the immunosuppression of acute myeloid leukemia, where they suppress the cytotoxic action of immune cells such as NK cells and T cells. This study demonstrates a way to achieve effective inhibition of immunosuppression by loading the drug histamine dihydrochloride (HDC) onto graphene quantum dots (GQDs) using hyaluronic acid as a targeting moiety for K-562 cells.

Multifunctional Inorganic Nanoparticles: Recent Progress in Thermal Therapy and Imaging.

Nanotechnology has enabled the development of many alternative anti-cancer approaches, such as thermal therapies, which cause minimal damage to healthy cells. Current challenges in cancer treatment are the identification of the diseased area and its efficient treatment without generating many side effects. Image-guided therapies can be a useful tool to diagnose and treat the diseased tissue and they offer therapy and imaging using a single nanostructure.

Mucoadhesive Chitosan Derivatives as Novel Drug Carriers.

Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route).

Polysaccharide-Coated Magnetic Nanoparticles for Imaging and Gene Therapy.

Today, nanotechnology plays a vital role in biomedical applications, especially for the diagnosis and treatment of various diseases. Among the many different types of fabricated nanoparticles, magnetic metal oxide nanoparticles stand out as unique and useful tools for biomedical applications, because of their imaging characteristics and therapeutic properties such as drug and gene carriers. Polymer-coated magnetic particles are currently of particular interest to investigators in the fields of nanobiomedicine and fundamental biomaterials.