Title:Passive Targeting of Cyclophosphamide-Loaded Carbonate Apatite Nanoparticles to Liver Impedes Breast Tumor Growth in a Syngeneic Model
Volume: 22
Issue: 37
Author(s): Snigdha Tiash and Md Ezharul H. Chowdhury
Affiliation:
Keywords:
Cyclophosphamide, breast cancer, carbonate apatite, nanoparticles, bio-distribution, cytotoxicity, tumor regression, immunocompetent
mouse.
Abstract: Despite being widely used for treating cancer, chemotherapy is accompanied by
numerous adverse effects as a result of systemic distribution and nonspecific interactions of
the drugs with healthy tissues, eventually leading to therapeutic inefficacy and chemoresistance.
Cyclophosphamide (Cyp) as one of the chemotherapeutic pro-drugs is activated in
liver and used to treat breast cancer in high dose and in combination with other drugs. In an
attempt to reduce the off-target effects and enhance the therapeutic efficacy, pH-sensitive
carbonate apatite nanoparticles that had predominantly and size-dependently been localized
in liver following intravenous administration, were employed to electrostatically immobilize
Cyp and purposely deliver it to the liver for activation. Cyp-loaded particles formed by
simple 30 min incubation at 37ºC of the DMEM (pH 7.4) medium containing CaCl2 and
Cyp, enhanced in vitro cytotoxicity at different degrees depending on the cell types. The
size of the particles could be tightly controlled by the amount of CaCl2 required to prepare
the particles and thus the bio-distribution pattern inside different organs of the body. Unlike the small particles (~
200 nm), the large size particles (~ 600 nm) which were more efficiently accumulated in liver, significantly reduced
the tumor volume following intravenous injection in 4T1-induced murine breast cancer model at a very low
dose (0.17 mg/Kg) of the drug initially added for complex formation, thus shedding light on the potential applications
of the Cyp-loaded nano-formulations in the treatment of breast cancer.
