Language
English
Publication Date
6-1-2024
Journal
Journal of Controlled Release
DOI
10.1016/j.jconrel.2024.04.029
PMID
38648957
PMCID
PMC11705614
PubMedCentral® Posted Date
1-7-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we have developed liposomes (LPS) conjugated with CDH11 neutralizing antibody (antiCDH11) to target cell surface CDH11 and loaded these LPS with a BCL-2 inhibitor, Navitoclax (NAVI), to induce apoptosis of CDH11 expressing fibroblasts. The developed LPS were evaluated for physicochemical characterization, stability, in vitro therapeutic efficacy using dermal fibroblasts, and in vivo therapeutic efficacy in bleomycin-induced skin fibrosis model in mice. The findings from in vitro and in vivo studies confirmed that selectivity of LPS was improved towards CDH11 expressing myofibroblasts, thereby improving therapeutic efficacy with no indication of adverse effects. Hence, this novel research work represents a versatile LPS strategy that exhibits promising potential for treating skin fibrosis.
Keywords
Animals, Liposomes, Apoptosis, Fibrosis, Cadherins, Skin, Humans, Fibroblasts, Aniline Compounds, Sulfonamides, Bleomycin, Proto-Oncogene Proteins c-bcl-2, Mice, Inbred C57BL, Antibodies, Neutralizing, Mice, Male, Cadherin 11, Dermal fibrosis, Lipid nanoparticle, Myofibroblast, Scleroderma
Published Open-Access
yes
Recommended Citation
Bhatt, Himanshu N; Diwan, Rimpy; Estevao, Igor L; et al., "Cadherin-11 Targeted Cell-Specific Liposomes Enabled Skin Fibrosis Treatment by Inducing Apoptosis" (2024). Faculty and Staff Publications. 4183.
https://digitalcommons.library.tmc.edu/baylor_docs/4183