A Trojan Horse Delivery Vehicle Carrying siRNA Nanotherapeutics with Multiple Tumor Microenvironment Responsiveness Elicits Robust Antitumor Immune Responses In Situ via a "Self-Synergistic" Approach.

The potential of small interfering RNAs (siRNAs) in the treatment of malignant tumors has attracted increasing attention due to their inherent advantages. However, their therapeutic performance strongly depends on the efficiency of their cytoplasmic delivery in vivo by the delivery vehicle with good cellular permeability and histocompatibility. Herein, a polycationic carrier camouflaged with macrophage membrane (MPM) is constructed biomimetically, which is condensed from endogenous spermine monomers through diselenide bonds.

Tailoring biomimetic dual-redox-responsive nanoplexes for enhanced RNAi-synergized photodynamic cancer immunotherapy.

Despite the strong potential of RNA interference (RNAi) therapies, critical issues, such as poor permeability across biological membranes and efficacy of their delivery into the cytoplasm, remain to be addressed before their successful clinical application. The current study aimed to address these issues by constructing a biomimetic nanoplex with dual redox responsiveness, which is derived from a cationic polymer formed by the condensation of endogenous spermine monomers via diselenide bonds. The developed nanoplexes decomposed in response to the redox microenvironment in cancer cells, thereby avoiding accumulation toxicity and poor transfection efficiency owing to incomplete siRNA release.

Modulating Repolarization of Tumor-Associated Macrophages with Targeted Therapeutic Nanoparticles as a Potential Strategy for Cancer Therapy.

There are always some components in the tumor microenvironment (TME), such as tumor-associated macrophages (TAMs), that help tumor cells escape the body's immune surveillance. Therefore, this situation can lead to tumor growth, progression, and metastasis, resulting in low response rates for cancer therapy. Macrophages play an important role with strong plasticity and functional diversity.

Influencing factors and strategies of enhancing nanoparticles into tumors .

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action.

Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression.

Background: PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight.

Methods: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection.

Gastrointestinal Responsive Polymeric Nanoparticles for Oral Delivery of Insulin: Optimized Preparation, Characterization, and In Vivo Evaluation.

Gastrointestinal responsive polymeric nanospheres (NPs) based on hydroxypropyl methylcellulose phthalate were prepared using spontaneous emulsification solvent diffusion method for improved oral administration of insulin. The NPs prepared under optimized conditions have an encapsulation efficiency of 90% and a particle size of about 200 nm. In vitro drug release experiments demonstrated that the NPs exhibited a gradient release profile of loaded drug when the pH value gradually increased from 3.

Engineering Nanoparticles for Targeted Remodeling of the Tumor Microenvironment to Improve Cancer Immunotherapy.

Owing to the fast-paced growth and cross-infiltration of oncology, immunology and molecular biology, tumor immunotherapy technology represented by immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy has lately made remarkable advancements. In comparison with traditional chemotherapy, immunotherapy has the potential to elicit a stronger sustained antitumor immune response in those patients who have advanced malignant malignancies. In spite of the advancements made, a significant number of clinical research works have validated that an extensive proportion of cancer patients still manifest insensitivity to immunotherapy, primarily because of the immunomodulatory interactions between tumor cells and the immunosuppressive tumor microenvironment (TME), together mediating the immune tolerance of tumors and accordingly impacting the positive response to immunotherapy.

The π-π stacking-guided supramolecular self-assembly of nanomedicine for effective delivery of antineoplastic therapies.

In traditional nano drug-delivery systems, the complex chemical bonds between drug and carrier often complicate the preparation process and are less prone to rupture upon entry into the target, which is detrimental to the timely release of the drug. The π-π stacking provides us with a promising alternative as it is a weak interaction between the aromatic rings. Since most antitumor drugs are hydrophobic molecules with complex aromatic π-π-conjugated structures, the construction of self-assembly based on π-π stacking between drugs and carriers has the advantage of improving the stability and drug loading capacity as well as the improvement of hydrophilicity and biosafety.

Inorganic kernel - Supported asymmetric hybrid vesicles for targeting delivery of STAT3-decoy oligonucleotides to overcome anti-HER2 therapeutic resistance of BT474R.

As a recombinant humanized monoclonal antibody that targets the extracellular region of HER2 tyrosine kinase receptor, trastuzumab (TRAZ) has demonstrated comparable clinical efficacy and improved survival in patients with HER2-positive breast cancer. Nevertheless, the therapeutic potential of TRAZ is often limited due to its frequent resistance to anti-HER2 therapy. Therefore, we investigate the reversal effect of STAT3-specific decoy oligonucleotides (STAT3-decoy ODNs) on TRAZ resistance, which contain the consensus sequence within the targeted gene promoter of STAT3.