Ramesh Chaudhari

Breast cancer, particularly the HER2 positive subtype, presents a formidable challenge in clinical oncology, necessitating innovative therapeutic strategies. Here, we present a novel immunoliposome-based formulation designed for targeted delivery of paclitaxel and miRNA inhibitors to HER2-positive breast cancer cells. Through a rigorous preclinical evaluation encompassing in vitro cellular studies and an in vivo tumor xenograft model, we demonstrate the formulation's remarkable efficacy in inhibiting cell proliferation, inducing apoptosis, and suppressing tumor growth. Histopathological assessments reveal a favourable safety profile with minimal adverse effects on normal tissues. Furthermore, the study unveils the synergistic interaction between paclitaxel and miRNA inhibitor within the formulation, offering a potential avenue for combination therapy. The novelty of the study lies in the development of a precise and targeted therapeutic approach tailored to HER2-positive breast cancer, addressing critical gaps in current treatment modalities. Our findings underscore this innovative formulation's clinical relevance and translational potential, paving the way for personalised and effective therapies in HER2-positive breast cancer management.

Nanocarrier-based targeting tumor-associated macrophages can reprogram pro-tumor M2 macrophages into anti-tumor M1 macrophages, offering a promising approach for advanced breast cancer treatment. Image created in BioRender.com.

Discover the groundbreaking potential of nanotech-based targeted delivery in breast cancer therapy. Our review showcases how this innovative precision medicine approach can revolutionise treatment and improve patient outcomes.

The versatile nature of macrophages and their ability to switch between various activation states plays a pivotal role in both promoting and inhibiting inflammatory processes. In pathological inflammatory conditions, classically activated M1 macrophages are often associated with initiating and maintaining inflammation, while alternatively activated M2 macrophages are linked to the resolution of chronic inflammation. Achieving a favorable equilibrium between M1 and M2 macrophages is crucial for mitigating inflammatory environments in pathological conditions. Polyphenols are known to have strong inherent antioxidative capabilities, and curcumin has been found to reduce macrophage inflammatory reactions. However, its therapeutic efficacy is compromised due to its poor bioavailability. The present study aims to harness the properties of curcumin by loading it in nanoliposomes and enhancing the M1-to-M2 macrophage polarization. A stable liposome formulation was achieved at 122.1 ± 0.08 nm, and a sustained kinetic release of curcumin was observed within 24 h. The nanoliposomes were further characterized using TEM, FTIR, and XRD, and the morphological changes in macrophage cells, RAW264.7, were observed in SEM, indicating a distinct M2-type phenotype after the treatment with liposomal curcumin. ROS may partially control macrophage polarization and be observed to decrease after treatment with liposomal curcumin. The nanoliposomes were able to successfully internalize in the macrophage cells, and an enhanced expression of ARG-1 and CD206 with a decrease in iNOS, CD80, and CD86 levels suggested the polarization of LPS-activated macrophages toward the M2 phenotype. Also, liposomal curcumin treatment dose-dependently inhibited TNF-α, IL-2, IFN-γ, and IL-17A at secretory levels and simultaneously increased the levels of cytokines like IL-4, IL-6, and IL-10.

Targeted medication delivery to the organ, tissue, or cells currently offers great opportunities in the field of drug therapy. Drug delivery systems (DDS) are essential for improving the efficacy of chemotherapy in cancer treatment. Chemotherapy is a subject of great interest since new drug delivery techniques are constantly being created. The ability of therapeutic agents to reach their intended sites and their low accumulation in non-specific sites (healthy organs and tissues) are both crucial components of anti-tumor chemotherapy success. As a result, the targeted distribution of medications to the organs, tissues, or cells is currently thought to provide wonderful prospective in the field of chemotherapy. The fundamental idea behind targeted delivery is that molecules that can be recognised by a specific receptor on cells or target sites can be used to modify delivery systems (such as the vector, containers, and others) rather than just the medication itself. These are therefore referred to as "targeted drug delivery systems." Yet, the development of multifunctional nanocarriers, such as nanoparticles, liposomes, micelles, dendrimers, and others, can greatly improve the effectiveness of numerous therapeutic and diagnostic procedures.

Transdermal immunization exhibits poor immunogenic responses due to poor permeability of antigens through the skin. Elastic liposomes, the ultradeformable nanoscale lipid vesicles, overcome the permeability issues and prove a versatile nanocarrier for transcutaneous delivery of protein, peptide, and nucleic acid antigens. Elastic liposome-mediated subcutaneous delivery of chimeric fusion protein (PfMSP-Fu₂₄) of Plasmodium falciparum exhibited improved immunogenic responses. Elastic liposomes-mediated immunization of PfMSP-Fu₂₄ conferred immunity to the asexual blood-stage infection. Present study is an attempt to compare the protective immune response mounted by the PfMSP-Fu₂₄ upon administered through transdermal and intramuscular routes. Humoral and cell-mediated immune (CMI) response elicited by topical and intramuscularly administered PfMSP-Fu₂₄-laden elastic liposomes (EL-PfMSP-Fu₂₄) were compared and normalized with the vehicle control. Sizeable immune responses were seen with the transcutaneously immunized EL-PfMSP-Fu₂₄ and compared with those elicited with intramuscularly administered antigen. Our results show significant IgG isotype subclass (IgG1and IgG3) response of specific antibody levels as well as cell-mediated immunity (CMI) activating factor (IFN-γ), a crucial player in conferring resistance to blood-stage malaria in mice receiving EL-PfMSP-Fu₂₄ through transdermal route as compared to the intramuscularly administered formulation. Heightened immune response obtained by the vaccination of EL-PfMSP-Fu₂₄ was complemented by the quantification of the transcript (mRNA) levels cell-mediated (IFN-γ, IL-4), and regulatory immune response (IL-10) in the lymph nodes and spleen. Collectively, elastic liposomes prove their immune-adjuvant property as they evoke sizeable and perdurable immune response against PfMSP-Fu₂₄ and justify its potential for the improved vaccine delivery to inducing both humoral and CM immune response.