Nano Research & Applications

Description

An admirable anti-cancer effect could be achieved by knocking down the UBC12 with siRNA, which would significantly suppress the neddylation pathway. However, a pressing issue is how to transport siRNA in vivo with low potential toxicity. For siRNA delivery, a folic acid (FA)-modified PLGA (poly(lactic-co-glycolic acid))-TK (thioketal)-PEG (polyethylene glycol) nanomedicine was developed. This was done with the intention of increasing the bioavailability of siRNA. The nano-vector has a spherical shape and is very biocompatible. The genetic nanomedicine was triggered by a high level of reactive oxygen species (ROS) and released its cargo siRNA in the tumor microenvironment following targeted endocytosis in liver cancer cells through selective recognition of FA and its receptor. By breaking down UBC12, suppressing the Neddylation pathway, and accumulating tumor-suppressive CRL substrates, the genetic nanomedicine not only inhibits proliferation and promotes apoptosis in liver cancer cells but also possesses excellent therapeutic efficacy. As a result, this work offers a novel strategy for creating a biodegradable nanomedicine with smart response and targeted recognition. In addition, it inhibits liver cancer cells' viability with high efficacy and low potential toxicity. The PLGA nanomedicine, in particular, exemplifies the encouraging potential of a multifunctional nanosystem that can be used to treat cancer. Active targeting with nanocarriers containing biological ligands has recently emerged as a novel method for enhancing the delivery of imaging and/or therapeutic agents to tumor cells.

Surface of Nanoparticles

It has been demonstrated that the presence of active targeting moieties on the surface of nanomedicines enhances their accumulation in tumoral cells and tissues in comparison to healthy ones.Both the therapeutic index and the potential adverse effects of the nanocarriers designed by this property can be reduced. The potential application of anti-EGFR immunotherapy and EGFR-targeting ligands in active targeting nanomedicines is receiving increasing attention due to the prevalence of EGFR overexpression, which is linked to the progression of a wide range of cancers. The EGFR-targeted nanomedicines have since undergone extensive in vitro and in vivo research, with varying degrees of success and failure depending on the protocols used. The purpose of this review is to provide an overview of the various EGFR-targeting ligands that are available for use in nanomedicines, how to conjugate them onto the surface of nanoparticles, and the primary analytical techniques that can be used to verify that this conjugation is successful. Smart nano-vehicles, which are capable of delivering active pharmaceutical ingredients to enhance their efficacy through any route of administration and in the most diverse therapeutic applications, are the focus of research in pharmaceutical nanotechnology. New nanopharmaceuticals' design and development can be time-consuming and labor-intensive. The use of mathematical, statistical, and computational tools has emerged as a useful strategy for this purpose in recent years.

In order to guarantee the quality of pharmaceutical products and enhance laboratory bench translational research into useful therapeutics, Quality by Design (QbD) tools have been implemented. A collection of fundamental concepts, a historical overview, and the application of QbD in nanomedicine are discussed in this overview. Response Surface Methodology and Artificial Neural Network approaches in general, as well as their use in the development of nanomedicine to monitor process parameters and obtain an optimized system ensuring its quality profile, have received special attention. An intimate link between SNAI1 and tumor malignancy has been discovered through molecular insights into tumorigenesis. We utilized the RNA interference tool (shSNAI1) and the chemotherapeutic drug doxorubicin in this study to investigate the advantages of SNAI1-knockdown in the treatment of tumors. Pullulan was attempted to be covalently conjugated with a number of functional moieties due to its abundance of hydroxyl groups. These functional moieties included positively-charged oligoethylenimine components for electrostatic entrapment of polyanionic shSNAI1 and hydrophobic components for lipophilic doxorubicin entrapment. Redox disulfide linkage was used to tailor the aforementioned covalent conjugations to be detachable in response to an intracellular reducing microenvironment, which accounts for the selective intracellular liberation of the therapeutic payloads. In addition, hyaluronic acid was used to modify the surface of the nanomedicine, providing it with excellent biocompatibility as well as active tumor-targeting function because its receptors (CD44) are overexpressed on tumor cells.

Mesoporous Organosilica Nanoplatforms

A significant role for SNAI1-knockdown in increasing chemotherapeutic potencies was found in subsequent studies, which also confirmed the systemic administration of shSNAI1 and doxorubicin into solid lung tumors in a highly targeted manner. The tumor vasculature poses a significant obstacle to the effective administration of cancer nanomedicine into tumors. The limited extravasation of nanomedicine into the tumor microenvironment (TME) may be attributable to the utilization of a passive pathway through interendothelial gaps in the blood vessels of the tumor. To target luminal endothelial cells caveolar Annexin-A1 protein and to initiate the active trans-endothelial transcytosis of nanomedicine mediated by caveolae, mesoporous organosilica nanoplatforms containing immunotherapeutics of anti-PD-L1 antibody (aPD-L1) and Indoximod are developed here. This method makes it possible for nanomedicines to spread quickly through the endothelium of the tumor and accumulate fairly extensively in the interstitium of the tumor.aPD-L1 and Indoximod release in a reduction-responsive manner, synergistically facilitating the intratumoral infiltration of cytotoxic T lymphocytes and reversing the immunosuppressive TME. As a result, they demonstrate significant anti-tumor efficacy in subcutaneous 4T1 breast tumors and remarkable anti-metastatic capacity to extend the survival of the 4T1 tumor metastasis model. In addition, nanomedicine is able to significantly slow the progression of orthotopic lung cancers caused by urethane more effectively than free drug combinations. Neoplasms with a poor prognosis known as hepatocellular carcinomas (HCCs) are highly vascularized. The delivery of diagnostics and therapeutics through nanomedicine holds enormous promise.

The fact that we have for the first time observed the Raman responses of mice with HCC tumor tissues to MTVDA-encapsulated non-targeted, targeted, and MTVDA-targeted cetuximab polymeric nanocomplexes delivering combinatorial therapeutics is a novel aspect of this research. Apoptotic lipid bodies and distinctive amide-I characteristics were the most clearly defined biochemical features. Tissues of the healthy liver and the HCC tumor could be stratified. For anticancer nanomedicine distinct stratification of MTVDA encapsulated targeted cetuximab polymeric nanocomplex combinatorials, a significant potential for HCC therapeutic monitoring, Raman spectroscopy served as an excellent, quick, sensitive, and cost-effective method. Inflammation of the heart muscle is the hallmark of myocarditis, which raises the risk of heart failure and dilated cardiomyopathy. As a major histopathological feature of myocarditis, macrophage migration is a potential therapeutic target for the treatment of this condition. We created a bioinspired anti-inflammatory nanomedicine (PSL-G) conjugated with protein G that had the potential to target macrophages and polarize them from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. PSL-G had a notable preference for macrophages over non-macrophage cells. In macrophages treated with lipopolysaccharide and/or interferon-, the addition of PSL-G raised the level of the anti-inflammatory cytokine IL-10 but decreased the level of pro-inflammatory cytokines like IL-1, IL-6, and TNF-.In addition, PSL-G's lifespan in murine blood circulation was found to be significantly longer than PSL's. In a mouse model of experimental autoimmune myocarditis, systemic injection of PSL-G significantly reduced myocardial fibrosis and macrophage migration (16 times lower than in the positive control group).We believe that bioinspired macrophage-targeted anti-inflammatory nanomedicines may be effective therapeutic options for the treatment of autoimmune and autoinflammatory diseases, particularly myocarditis, based on these findings and the fact that macrophages play a crucial role in the pathogenesis of various diseases. Although the development of nanomedicines for the treatment of breast cancer has received a great deal of attention, the therapeutic efficacy is far from satisfactory due to non-specific biodistribution-caused side effects and the limitations of single-modal treatment. A novel nanomedicine for effective combination breast cancer treatment has been developed in this study. Copper-doped layered double hydroxide (Cu-LDH) nanoparticles with albumin-bound paclitaxel (nAb-PTX) and 5-fluorouracil (5-FU)—two FDA-approved anticancer drugs with complementary chemotherapeutic effects—constituted the basis of this nanomedicine. The nanomedicine demonstrated pH-sensitive heat-facilitated therapeutic on-demand release and moderate-to-strong synergy between photothermal therapy and chemotherapy in the induction of breast cancer cell apoptosis (4 T1). This nanomedicine efficiently accumulated in the tumor tissue and had a high colloidal stability in serum and saline. Amazingly, this nanomedicine nearly killed four T1 tumors in vivo after two courses of treatment with very low doses of 5-FU and nAb-PTX (0.25 and 0.50 mg/kg, 8–50 times less than in other nanoformulations) under mild 808 nm laser irradiation (0.75 W/cm2, 3 min). As a result, this study offers a novel method for designing multifunctional nanomedicines with on-demand chemotherapeutic release to treat breast cancer at a low cost and with few side effects in future clinical applications.