Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond

Abstract

Breast cancer (BC) is the second most frequent cause of death among women. Representing a complex and heterogeneous type of cancer, its occurrence is attributed by both genetic (gene mutations, e.g., BRCA1, BRCA2) and non-genetic (race, ethnicity, etc.) risk factors. The effectiveness of available treatment regimens (small molecules, cytotoxic agents, and inhibitors) decreased due to their poor penetration across biological barriers, limited targeting, and rapid body clearance along with their effect on normal resident cells of bone marrow, gastrointestinal tract, and hair follicles. This significantly reduced their clinical outcomes, which led to an unprecedented increase in the number of cases worldwide. Nanomedicine, a nano-formulation of therapeutics, emerged as a versatile delivering module for employment in achieving the effective and target specific delivery of pharmaceutical payloads. Adoption of nanotechnological approaches in delivering therapeutic molecules to target cells ensures not only reduced immune response and toxicity, but increases the stability of therapeutic entities in the systemic circulation that averts their degradation and as such increased extravasations and accumulation via enhanced permeation and the retention (EPR) effect in target tissues. Additionally, nanoparticle (NP)-induced ER stress, which enhances apoptosis and autophagy, has been utilized as a combative strategy in the treatment of cancerous cells. As nanoparticles-based avenues have been capitalized to achieve better efficacy of the new genera of therapeutics with enhanced specificity and safety, the present study is aimed at providing the fundamentals of BC, nanotechnological modules (organic, inorganic, and hybrid) employed in delivering different therapeutic molecules, and mechanistic insights of nano-ER stress induced apoptosis and autophagy with a perspective of exploring this avenue for use in the nano-toxicological studies. Furthermore, the current scenario of USA FDA approved nano-formulations and the future perspective of nanotechnological based interventions to overcome the existing challenges are also discussed.

IL-38 gene expression: A new player in Graves’ ophthalmopathy patients in Iraq

“…This is accomplished by reducing the activation of selfreactive T cells and delaying the beginning of illness. This disorder manifests itself in a patient whenever their immune system begins to attack their own body (22). These findings provide credence to the findings by (23), who found that the blood IL-38 concentrations of individuals with Graves' disease and Hashimoto's illness were significantly different from those of healthy controls.…”

Nuclear Mechanisms Involved in Endocrine Resistance

“…The importance of UPR for drug resistance has planted the idea of inducing an overload of ER stress (166). This could be achieved by certain nanoparticles or by the proteasome inhibitor bortezomib, the latter being already used to treat certain haematopoietic cancers.…”

Interaction of Graphene Oxide Particles and Dendrimers with Human Breast Cancer Cells by Real-Time Microscopy

“…Several authors have already reported that the non-covalent conjugation of anticancer molecules with graphene oxide sheets may be the path to more targeted delivery at the cellular level and a possible escape from tumor resistance [ 7 , 8 ]. Structural modification aimed at solving these limitations and reducing the cytotoxicity of the material is an interesting strategy for the biological applications of graphene [ 9 ]. Among the possible structural modifications in graphene particles, the association with dendrimers, such as polyamide amine (PAMAM), can provide better cell uptake since PAMAM dendrimers have been reported to be able to associate electrostatically with lipid membranes to form amphiphilic bilayers and thus promote cell uptake [ 10 , 11 , 12 ].…”