Combined chemo-magnetic field-photothermal breast cancer therapy based on porous magnetite nanospheres

Abstract

The efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance.

Laser-triggered combined chemotherapy and photodynamic therapy enabled by iron sulfide-doxorubicin@bovine lactoferrin nanozymes for breast cancer therapy

“…In addition to the release of Fe 2+ and H 2 S, Dox loaded on FeS-Dox@bLf NZs will be very effective on therapeutic activity. In agreement with the results of Singh, et al [51], Shari , et al [6], and Shari , et al [8] Fig. 2H shows that the release of Dox from FeS-Dox@bLf NZs increases with decreasing environmental acidity.…”

“…The physicochemical properties of FeS NZs were consistent with the ndings of Sathiyaraj and Thirumaran [38] and Yang, et al [39]. On the other hand, the results of SEM, TEM and FTIR similar to the outcomes of Shankaranarayanan, et al [40] and Shari , et al [8] showed that bLf and Dox were loaded on FeS NZs. Metallic NPs such as Fe, manganese (Mn), copper (Cu), etc.…”

Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand

“… [ 126 ] Mesoporous Fe 3 O 4 @SiO 2 NPs Mesoporous maghemite NPs DOX Combined DOX/magnetic/PTT therapy significantly inhibited growth and metastasis of breast cancer to lung while reduced cardiotoxicity. [ 127 , 128 ] GO@Fe 3 O 4 Nanocomposites DOX Increased cytotoxic efficacy to glioma cells. [ 129 ] Graphene nanosponge-supported lipid bilayer DTX PFH LF conjugation increased the tumor accumulation and penetration of NPs by increasing its bilayer fluidity.…”

“…Porous magnetic NPs showed excellent capacity of absorbing magnetic and optical wavelengths resulting in heat generation to kill cancer cells. Therefore, mesoporous Fe 3 O 4 @SiO 2 NPs (PMNSs) and maghemite NPs (MMNPs) were synthesized by hydrothermal method then chemically modified with Lf for tumor targeting and then physically loaded with DOX [ 127 , 128 ]. The combination of chemo- and photothermal/magnetic therapy showed enhanced antitumor efficacy.…”

“…By virtue of their superparamagnetic properties, FebLf NCs can be considered as suitable cancer nanotheranostic agent for MRI contrast imaging and magnetic guided cancer therapy. In another investigation, Lf-coated DOX-loaded porous magnetite nanospheres (PMNSs) were developed for synergistic chemo-magnetic field photothermal therapy of breast cancer [ 190 ]. The injected Lf-DOX-PMNSs significantly into 4T1 bearing mice suppressed the proliferation of 4T1 cells and tumor weight by activating both the extrinsic pathway of apoptosis via upregulation of the TNF-α mRNA and enhancing the intrinsic Bax mRNA expression.…”