Journal
ACS APPLIED BIO MATERIALS
Volume 3, Issue 10, Pages 7067-7079Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.0c00913
Keywords
nanomicelles; conjugation; niclosamide; targeted cancer therapy; STAT-3; cancer stem cells
Funding
- Department of Biotechnology, Government of India
- DST-INSPIRE, Department of Science and Technology, Government of India
- IPD fellowship, IIT Bombay
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Site-selective uptake and specific biodistribution of chemotherapeutic drugs are essential prerequisites for targeted cancer therapy. Especially, antibody and peptide conjugated drugs have been attempted as localized therapeutic agents. However, the characteristics of drug conjugated nanosystems are less explored, which are limited with their toxicity, low therapeutic efficacy, complicated synthesis, and high costs. Herein, we report a biocompatible (about 95%) molecularly engineered anticancer drug conjugated nanomicelles (similar to 200 nm in size) for site-selective CD44 overexpressed cancer cell rupture and tumor growth inhibition. Microscopic analysis demonstrates the distinct visualization of organic-organic interfaces (similar to 5 nm), which are corroborated with spectroscopic measurements confirmed the conjugation of niclosamide drug with hyaluronic acid (NIC-HA). Uniformly distributed hemocompatible (about 99%) organic nanomicelles exhibit the cellular membrane and cytoplasmic targeting with significant cellular rupture (IC50 of 4 mu M for MDA MB 231 cells) indicating their inherent targeting ability for cancer cells and cancer stem cells. An inclusive in vitro and in vivo analysis for targeted antitumor activity (HT1080 tumor xenograft model) of NIC-HA nanoconjugates (similar to 24.6% loading) exhibited promising cancer cell death and tumor growth inhibition (60%, p < 0.05) due to STAT-3 signaling pathway inhibition and induction of apoptosis in CD44-positive triple negative breast cancer cells.
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